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

PubMed

Barkla, D H; Tutton, P M

1983-10-01

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

Antioxidant and anti-atherogenic activities of three Piper species on atherogenic diet fed hamsters.

PubMed

Agbor, Gabriel A; Vinson, Joe A; Sortino, Julianne; Johnson, Robert

2012-05-01

Atherogenic diet is known to induce high plasma lipid concentration, oxidative stress and early atherosclerosis. Antioxidants have potentials to counter the effect of atherogenic diet. The present research aims at evaluating the antioxidant and anti-atherosclerotic activities of three Piper species (Piper guineense, Piper nigrum and Piper umbellatum) on atherogenic diet fed hamsters. Hamsters divided into 8 groups: normal control, atherosclerotic control and six test groups. The normal animals fed normal rodent chow, the atherosclerotic control animals fed the same rodent chow supplemented with 0.2% cholesterol and 10% coconut oil (high cholesterol diet). The 6 test groups' animals fed same diet as the atherosclerotic control group but with additional supplementation of 2 graded doses (1 and 0.25 mg/kg body weight, o.p.) of plant extracts for 12 weeks. The atherogenic diet induced a collapse of the erythrocyte antioxidant defense system (significant decrease in superoxide dismutase, catalase and glutathione peroxidase activities). Atherogenic diet also induced an increase in plasma total cholesterol, triglyceride, thiobarbituric acid reactive substances (TBARS), oxidation of low density lipoprotein cholesterol (LDL) and accumulation of foam cells in the aorta a hall mark for atherosclerosis. Administration of the Piper species prevented the collapse of the antioxidant system and the increase of plasma parameters maintaining them towards normality. The Piper species also prevented LDL oxidation by increasing the time (lag time) for its oxidation. The results suggest that these Piper species have significant antioxidant and anti-atherogenic effect against atherogenic diet intoxication. Copyright © 2010 Elsevier GmbH. All rights reserved.

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets.

PubMed

Sá, M A; Andrade, V B; Mendes, R M; Caliari, M V; Ladeira, L O; Silva, E E; Silva, G A B; Corrêa-Júnior, J D; Ferreira, A J

2013-07-01

We evaluated the effects of sodium hyaluronate (HY) and carbon nanotubes functionalized with HY (HY-CNT) on bone repair in the tooth sockets of diabetic rats. Diabetes was induced by streptozotocin (50 mg kg(-1) i.v.), and the sockets were divided into normal control, diabetic control, diabetic treated with HY (1%), and diabetic treated with HY-CNT (100 μg ml(-1)) groups. The sockets were analyzed according to the percentage of bone formation and the number of cell nuclei. The percentage of bone trabeculae was lower in diabetic control animals (11.16 ± 5.10% vs 41.92 ± 6.34% in normal animals) after 14 days. Treating diabetic animals with HY or HY-CNT significantly increased the percentage of neoformed trabeculae (HY: 29.43 ± 3.29%; HY-CNT: 36.90 ± 3.07%). Moreover, the sockets of diabetic animals had an increased number of cell nuclei and HY or HY-CNT reduced this parameter. Our results indicate that HY and HY-CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Use of Interactive Computer Animations Based on POE as a Presentation Tool in Primary Science Teaching

NASA Astrophysics Data System (ADS)

Akpınar, Ercan

2014-08-01

This study investigates the effects of using interactive computer animations based on predict-observe-explain (POE) as a presentation tool on primary school students' understanding of the static electricity concepts. A quasi-experimental pre-test/post-test control group design was utilized in this study. The experiment group consisted of 30 students, and the control group of 27 students. The control group received normal instruction in which the teacher provided instruction by means of lecture, discussion and homework. Whereas in the experiment group, dynamic and interactive animations based on POE were used as a presentation tool. Data collection tools used in the study were static electricity concept test and open-ended questions. The static electricity concept test was used as pre-test before the implementation, as post-test at the end of the implementation and as delay test approximately 6 weeks after the implementation. Open-ended questions were used at the end of the implementation and approximately 6 weeks after the implementation. Results indicated that the interactive animations used as presentation tools were more effective on the students' understanding of static electricity concepts compared to normal instruction.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

PubMed

Poirier, Guillaume L; Huang, Wei; Tam, Kelly; DiFranza, Joseph R; King, Jean A

2017-09-01

Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

Bee, L A; Dickenson, A H

2007-07-13

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

Reference genes for quantitative PCR in the adipose tissue of mice with metabolic disease.

PubMed

Almeida-Oliveira, Fernanda; Leandro, João G B; Ausina, Priscila; Sola-Penna, Mauro; Majerowicz, David

2017-04-01

Obesity and diabetes are metabolic diseases and they are increasing in prevalence. The dynamics of gene expression associated with these diseases is fundamental to identifying genes involved in related biological processes. qPCR is a sensitive technique for mRNA quantification and the most commonly used method in gene-expression studies. However, the reliability of these results is directly influenced by data normalization. As reference genes are the major normalization method used, this work aims to identify reference genes for qPCR in adipose tissues of mice with type-I diabetes or obesity. We selected 12 genes that are commonly used as reference genes. The expression of these genes in the adipose tissues of mice was analyzed in the context of three different experimental protocols: 1) untreated animals; 2) high-fat-diet animals; and 3) streptozotocin-treated animals. Gene-expression stability was analyzed using four different algorithms. Our data indicate that TATA-binding protein is stably expressed across adipose tissues in control animals. This gene was also a useful reference when the brown adipose tissues of control and obese mice were analyzed. The mitochondrial ATP synthase F1 complex gene exhibits stable expression in subcutaneous and perigonadal adipose tissue from control and obese mice. Moreover, this gene is the best reference for qPCR normalization in adipose tissue from streptozotocin-treated animals. These results show that there is no perfect stable gene suited for use under all experimental conditions. In conclusion, the selection of appropriate genes is a prerequisite to ensure qPCR reliability and must be performed separately for different experimental protocols. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Is Wildlife Fertility Control Always Humane?

PubMed Central

Hampton, Jordan O.; Hyndman, Timothy H.; Barnes, Anne; Collins, Teresa

2015-01-01

Simple Summary There are various fertility control methods (modalities) currently available that aim to reduce the abundance of problematic free-ranging mammalian wildlife. Here, we propose that dissimilarities in the mechanism of action indicate these methods produce great variation in animal welfare outcomes. We present a framework to assist managers in minimising animal welfare risks. Abstract Investigation of fertility control techniques to reduce reproductive rates in wildlife populations has been the source of much research. Techniques targeting wildlife fertility have been diverse. Most research into fertility control methods has focused upon efficacy, with few studies rigorously assessing animal welfare beyond opportunistic anecdote. However, fertility control techniques represent several very different mechanisms of action (modalities), each with their own different animal welfare risks. We provide a review of the mechanisms of action for fertility control methods, and consider the role of manipulation of reproductive hormones (“endocrine suppression”) for the long-term ability of animals to behave normally. We consider the potential welfare costs of animal manipulation techniques that are required to administer fertility treatments, including capture, restraint, surgery and drug delivery, and the requirement for repeated administration within the lifetime of an animal. We challenge the assumption that fertility control modalities generate similar and desirable animal welfare outcomes, and we argue that knowledge of reproductive physiology and behaviour should be more adeptly applied to wild animal management decisions. We encourage wildlife managers to carefully assess long-term behavioural risks, associated animal handling techniques, and the importance of positive welfare states when selecting fertility control methods as a means of population control. PMID:26506395

[Effects of soybean isoflavone on born metabolism and morphology in animal model of osteoporosis rats].

PubMed

Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li

2007-07-01

To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.

40 CFR 79.67 - Glial fibrillary acidic protein assay.

Code of Federal Regulations, 2011 CFR

2011-07-01

... immunoreactivity of individual samples (both control and exposed groups) with that of the sample used to generate... the control groups is normalized to 100 percent and all data are expressed as a percentage of control... emission-exposed and unexposed control animals. It is based on modifications (O'Callaghan & Miller 1985 in...

40 CFR 79.67 - Glial fibrillary acidic protein assay.

Code of Federal Regulations, 2014 CFR

2014-07-01

... immunoreactivity of individual samples (both control and exposed groups) with that of the sample used to generate... the control groups is normalized to 100 percent and all data are expressed as a percentage of control... emission-exposed and unexposed control animals. It is based on modifications (O'Callaghan & Miller 1985 in...

40 CFR 79.67 - Glial fibrillary acidic protein assay.

Code of Federal Regulations, 2012 CFR

2012-07-01

... immunoreactivity of individual samples (both control and exposed groups) with that of the sample used to generate... the control groups is normalized to 100 percent and all data are expressed as a percentage of control... emission-exposed and unexposed control animals. It is based on modifications (O'Callaghan & Miller 1985 in...

40 CFR 79.67 - Glial fibrillary acidic protein assay.

Code of Federal Regulations, 2010 CFR

2010-07-01

... immunoreactivity of individual samples (both control and exposed groups) with that of the sample used to generate... the control groups is normalized to 100 percent and all data are expressed as a percentage of control... emission-exposed and unexposed control animals. It is based on modifications (O'Callaghan & Miller 1985 in...

40 CFR 79.67 - Glial fibrillary acidic protein assay.

Code of Federal Regulations, 2013 CFR

2013-07-01

... immunoreactivity of individual samples (both control and exposed groups) with that of the sample used to generate... the control groups is normalized to 100 percent and all data are expressed as a percentage of control... emission-exposed and unexposed control animals. It is based on modifications (O'Callaghan & Miller 1985 in...

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

PubMed

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

2002-08-01

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

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

PubMed

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

2011-10-01

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

Endocrine Profiles, Haematology and Pregnancy Outcomes of Late Pregnant Holstein Dairy Heifers Sired by Bulls Giving a High or Low Incidence of Stillbirth

PubMed Central

Kornmatitsuk, B; Dahl, E; Ropstad, E; Beckers, JF; Gustafsson, H; Kindahl, H

2004-01-01

The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth. Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with 3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology, placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2 followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition (<1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4 and PAGs were slightly lower during 30–50 days prior to delivery and increased with a lower magnitude at the time of parturition. In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins (PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in animals with a high risk of stillbirth at term. PMID:15535086

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Plasma lipids, lipoproteins, and triglyceride turnover in eu- and hypo-thyroid rats and rats on a hypocaloric diet.

PubMed

Dory, L; Krause, B R; Roheim, P S

1981-08-01

Lipid and lipoprotein concentration, and triglyceride turnover were studied in control, thyroidectomized, and pair-fed control rats (pair-fed to match the food intake of the thyroidectomized rats). Thyroidectomy induced a significant increase in plasma cholesterol (and low density lipoprotein) concentrations and a decrease in plasma triglyceride (and very low density lipoprotein) concentrations. Changes in similar direction but of smaller magnitude were observed in the plasma of the pair-fed control rats. To further investigate triglyceride metabolism in these three groups of animals, triglyceride turnover was studied in fasted, unrestrained, and unanesthetized rats, following injection of [2-3H]glycerol. Peak incorporation of [2-3H]glycerol into plasma triglyceride occurred in all three groups of animals at 25 min after precursor administration, although the maximal incorporation was substantially lower in the thyroidectomized group than in either of the control groups. Thereafter, plasma triglyceride radioactivity decayed monoexponentially with a half-life of 24 +/- 1 min for both normal and pair-fed control rats, compared with the half-life of 41 +/- 3 min observed in the thyroidectomized rats. The calculated apparent fractional catabolic rates were thus 0.029 min-1 for both control groups and only 0.017 min-1 for the thyroidectomized animals. The apparent total catabolic rates of plasma triglyceride were 299 +/- 11, 138 +/- 11, and 48 +/- 4 micrograms triglyceride . min-1 for the normal controls, pair-fed controls, and thyroidectomized rats, respectively. These data further emphasize the importance of thyroid hormones in regulating plasma lipid and lipoprotein metabolism and, specifically, indicate that hypothyroidism results in a reduction of triglyceride secretion into, and the removal from, circulation. Furthermore, evidence was presented that the decreased caloric intake of the hypothyroid animals cannot, in itself, account for this observation.

H2S induces a suspended animation-like state in mice.

PubMed

Blackstone, Eric; Morrison, Mike; Roth, Mark B

2005-04-22

Mammals normally maintain their core body temperature (CBT) despite changes in environmental temperature. Exceptions to this norm include suspended animation-like states such as hibernation, torpor, and estivation. These states are all characterized by marked decreases in metabolic rate, followed by a loss of homeothermic control in which the animal's CBT approaches that of the environment. We report that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species, the house mouse (Mus musculus). This state is readily reversible and does not appear to harm the animal. This suggests the possibility of inducing suspended animation-like states for medical applications.

Comparison of biochemical properties of liver arginase from streptozocin-induced diabetic and control mice.

PubMed

Spolarics, Z; Bond, J S

1989-11-01

Arginase activity is elevated in livers of diabetic animals compared to controls and there is evidence that this is due in part to increased specific activity (activity/mg arginase protein). To investigate the molecular basis of this increased activity, the physicochemical and kinetic properties of hepatic arginase from diabetic and control mice were compared. Two types of arginase subunits with molecular weights of 35,000 and 38,000 were found in both the diabetic and control animals and the subunits in these animals had similar, multiple ionic forms. Kinetic parameters of purified preparations of arginase for arginine (apparent Km and Vmax values) and the thermal stability of these preparations from diabetics and controls were also similar. Furthermore, no difference was found in the distribution of arginase activity among different subcellular liver fractions. Separation of basic and acidic oligomeric forms of arginase by fast-protein liquid chromatography resulted in a slightly different distribution of activity among the forms in the normal and diabetic group. The apparent Km values for Mn2+ of the basic form of the enzyme were 25 and 33 microM for the enzyme from normal and diabetic animals, respectively; for acidic forms, for which two apparent Km values were measured, the values were 8 and 197 microM for arginase from controls and 35 and 537 microM from diabetics. These results indicate that in diabetes, while no marked changes in the physicochemical characteristics of arginase are obvious, some changes are found in the interaction of arginase with its cofactor Mn.

Brief Report: The Smiles of a Child with Autism Spectrum Disorder during an Animal-Assisted Activity May Facilitate Social Positive Behaviors--Quantitative Analysis with Smile-Detecting Interface

ERIC Educational Resources Information Center

Funahashi, Atsushi; Gruebler, Anna; Aoki, Takeshi; Kadone, Hideki; Suzuki, Kenji

2014-01-01

We quantitatively measured the smiles of a child with autism spectrum disorder (ASD-C) using a wearable interface device during animal-assisted activities (AAA) for 7 months, and compared the results with a control of the same age. The participant was a 10-year-old boy with ASD, and a normal healthy boy of the same age was the control. They…

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

NASA Technical Reports Server (NTRS)

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

1982-01-01

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

Using an Animal Group Vigilance Practical Session to Give Learners a "Heads-Up" to Problems in Experimental Design

ERIC Educational Resources Information Center

Rands, Sean A.

2011-01-01

The design of experimental ecological fieldwork is difficult to teach to classes, particularly when protocols for data collection are normally carefully controlled by the class organiser. Normally, reinforcement of the some problems of experimental design such as the avoidance of pseudoreplication and appropriate sampling techniques does not occur…

78 FR 41716 - Hours of Service; Limited 90-Day Waiver From the 30-Minute Rest Break Requirement for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-11

..., is a significant concern to the agricultural industry. The animals face a variety of stresses... the transportation of pigs because these animals do not sweat and are subject to heat stress. When heat stress occurs, a pig's body temperature rises to a level that it cannot control through its normal...

In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats.

PubMed

Adetoro, Kadejo Olubukola; Bolanle, James Dorcas; Abdullahi, Sallau Balarebe; Ahmed, Ozigi Abdulrahaman

2013-05-01

The antioxidant effects of aqueous root bark, stem bark and leaves of Vitex doniana (V. doniana) were evaluated in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (148 mg·ml(-1)·kg(-1) body weight) as a 1:1 (v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of V. doniana and vitamin E as standard drug (100 mg/kg body weighy per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of three weeks. The liver of CCl4 induced not treated group showed that the induction with CCl4, significantly (P<0.05) increased thiobarbituric acid reactive substance (TBARS) and significantly (P<0.05) decreased superoxide dismutase (SOD) and catalase (CAT). However there was no significant (P>0.05) difference between TBARS, SOD and CAT in the liver of the induced treated groups and normal control group. In the kidney, TBARS showed no significant (P>0.05) difference between the normal and the induced groups, SOD was significantly (P<0.05) reduced in the CCl4 group compared to standard drug and normal control groups, CAT was significantly (P<0.05) increased in root and vitamin E groups when compared to induced not treated group. The studies also showed that when the extracts were administered to normal animals, there was no significant (P>0.05) change in the liver and kidney level of TBARS, SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly (P<0.05) lowered compared to control group. The result of the present study suggests that application of V. doniana plant would play an important role in increasing the antioxidant effect and reducing the oxidative damage that formed both in liver and in kidney tissues. However stem bark has potential to improve renal function in normal rats.

Blood harmane concentrations and dietary protein consumption in essential tremor.

PubMed

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

2005-08-09

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

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).

A comparative study of seminiferous tubular epithelium from rats flown on Cosmos 1887 and SL3

NASA Technical Reports Server (NTRS)

Sapp, Walter J.; Williams, Carol S.; Kato, K.; Philpott, Delbert E.; Stevenson, J.; Serova, L. V.

1989-01-01

Space flight, with its unique environmental constraints such as immobilization, decreased and increased pressures, and radiation, is known to affect testicular morphology and spermatogenesis. Among the several biological experiments and animals on board COSMOS 1887 Biosputnik flight were 10 rats, from which were collected testicular tissue. Average weights of flight tests were 6.4 pct. below that of the vivarium control when normalized for weight loss/100 grams body weight. Counts of surviving spermatogonia per tubule cross section indicated an average of 39 spermatogonia for flight animals, 40 for synchronous controls and 44 for the vivarium controls. Serum testosterone was significantly decreased when compared to basal controls but the decrease was not significant when compared in vivarium and synchronous control groups. The significant decrease in spermatogonia and the decrease in serum testosterone are similar to that in animals flown on Space Lab 3 (Challenger Shuttle).

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 2: Bone elongation rate and bone mass in metaphysis of long bones

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Kimmel, D. B.; Smith, C.; Dell, R. B.

1981-01-01

The proximal humeral metaphysis of rats from time periods recovery plus zero days (R+0), recovery plus six days (R+6), and recovery plus twenty nine days (R+29) was analyzed. The volume of calcified cartilage and bone in flight and synchronous controls was reduced in groups R+0 and R+6, but was normal in group R+29. The number of functional bone cells (osteoblasts and osteoclasts) was decreased in proportion to the amount of bone in the early groups, and was normal in the last group. The fatty marrow volume was increased only in flight animals of groups R+0 and R+6, but was normal in the R+29 group. Accumulation of excess fatty marrow was seen only in flight animals. The decreased amount of bone and calcified cartilage is believed to be the result of a temporarily slowed or arrested production of calcified cartilage as a substrate for bone formation. This would have resulted from slowed bone elongation during flight and synchronous control conditions. Bone elongation returned to normal by twenty nine days after return.

Novel Hg2+-Induced Nephropathy in Rats and Mice Lacking Mrp2: Evidence of Axial Heterogeneity in the Handling of Hg2+ Along the Proximal Tubule

PubMed Central

Zalups, Rudolfs K.; Joshee, Lucy; Bridges, Christy C.

2014-01-01

The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg2+) was studied in rats (TR−) and mice (Mrp2−/−), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg2+ were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects. PMID:25145654

Estrous Cyclicity of Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, Eric; Talyansky, Yuli; Scott, Ryan; Tash, Joseph; Christenson, Lane; Alwood, Joshua; Ronca, April

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n22), normally loaded HU Cage Pair-Fed controls (CPF; n22), and Vivarium controls fed ad libitum (VIV; n10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, andor due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5 vs 3.0, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system.

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

NASA Astrophysics Data System (ADS)

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

2007-02-01

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

Automatic real-time pair-feeding system for animals

NASA Technical Reports Server (NTRS)

Leon, H. A.; Connolly, J. P.; Hitchman, M. J.; Humbert, J. E. (Inventor)

1974-01-01

A pair feeding method and apparatus are provided for experimental animals wherein the amount of food consumed is immediately delivered to a normal or control animal so that there is a qualitative, quantitative and chronological correctness in the pair feeding of the two animals. This feeding mechanism delivers precisely measured amounts of food to a feeder. Circuitry is provided between master and slave feeders so that there is virtually no chance of a malfunction of the feeding apparatus, causing erratic results. Recording equipment is also provided so that an hourly record is kept of food delivery.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

PubMed

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-09-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

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

PubMed

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

1993-06-01

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

Blocking GABA-A receptors in the Medial Septum Enhances Hippocampal Acetylcholine Release and Behavior in a Rat Model of Diencephalic Amnesia

PubMed Central

Roland, Jessica J.; Savage, Lisa M.

2009-01-01

Wernicke-Korsakoff syndrome (WKS), a form of diencephalic amnesia caused by thiamine deficiency, results in severe anterograde memory loss. Pyrithiamine-induced thiamine deficiency (PTD), an animal model of WKS, produces cholinergic abnormalities including decreased functional hippocampal acetylcholine (ACh) release and poor spatial memory. Increasing hippocampal ACh levels has increased performance in PTD animals. Intraseptal bicuculline (GABAA antagonist) augments hippocampal ACh release in normal animals and we found it (0.50μg/μl & 0.75μg/μl) also increased in-vivo hippocampal ACh release in PTD animals. However, the 0.75 μg/μl dose produced a greater change in hippocampal ACh release in control animals. The 0.50μg/μl dose of bicuculline was then selected to determine if it could enhance spontaneous alternation performance in PTD animals. This dose of bicuculline significantly increased hippocampal ACh levels above baseline in both PTD and control rats and resulted in complete behavioral recovery in PTD animals, without altering performance in control rats. This suggests that balancing ACh-GABA interactions in the septohippocampal circuit may be an effective therapeutic approach in certain amnestic syndromes. PMID:19463263

Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

PubMed

Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

2007-02-01

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

PubMed Central

Van Den Berg, Pleuntje; Radl, J.; Löwenberg, B.; Swart, A. C. W.

1976-01-01

Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP–Rhesus albumin and IgA1λ-10S human paraprotein. One or more transient homogeneous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP–Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. ImagesFig. 1

Blood harmane concentrations and dietary protein consumption in essential tremor

PubMed Central

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

2016-01-01

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

Proliferation of protease-enriched mast cells in sarcoptic skin lesions of raccoon dogs.

PubMed

Noviana, D; W Harjanti, D; Otsuka, Y; Horii, Y

2004-07-01

Skin sites, tongue, lung, liver, jejunum and rectum from two raccoon dogs with Sarcoptes scabiei infestation and five normal (control) raccoon dogs were examined in terms of the distribution, proteoglycan properties and protease activity of mast cells. Infestation with S. scabiei caused a significant increase in the number of dermal mast cells. While the number of mast cells (average +/- standard deviation) in specimens of skin from the dorsum, dorsal neck, dorsal hind foot and dorsal fore foot was 40.0 +/- 19.8/mm2 in control animals, it was 236.1 +/- 58.9/mm2 in the skin of mange-infested animals. Histochemical analysis revealed the glycosaminoglycan, heparin, within the mast cells of all organs examined in both control and affected animals. Enzyme-histochemical detection of serine proteases demonstrated an increase in mast-cell-specific protease activity (i.e., chymase and tryptase) in the skin of infested animals. The percentage of mast cells demonstrating chymase activity was 53.0 +/- 27.4% in control animals and 73.8 +/- 19.4% in mite-infested animals. The corresponding results for tryptase activity were 53.5 +/- 25.2% and 89.4 +/- 9.8%. Increases in mast cell chymase or tryptase activity, or both, were also observed within other organs of the infected animals, but the total number of mast cells found at such sites (with the exception of liver and ventrolateral pinna) did not differ from those of control animals. Copyright 2004 Elsevier Ltd.

Deep cytoplasmic rearrangements in ventralized Xenopus embryos

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

XYLITOL IMPROVES ANTI-OXIDATIVE DEFENSE SYSTEM IN SERUM, LIVER, HEART, KIDNEY AND PANCREAS OF NORMAL AND TYPE 2 DIABETES MODEL OF RATS.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Shahidul

2017-05-01

The present study investigated the anti-oxidative effects of xylitol both in vitro and in vivo in normal and type 2 diabetes (T2D) rat model. Free radical scavenging and ferric reducing potentials of different concentrations of xylitol were investigated in vitro. For in vivo study, six weeks old male Sprague-Dawley rats were divided into four groups, namely: Normal Control (NC), Diabetic Control (DBC), Normal Xylitol (NXYL) and Diabetic Xylitol (DXYL). T2D was induced in the DBC and DXYL groups. After the confirmation of diabetes, a 10% xylitol solution was supplied instead of drinking water to NXYL and DXYL, while normal drinking water was supplied to NC and DBC ad libitum. After five weeks intervention period, the animals were sacri- ficed and thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) concentrations as well as superoxide dismutase, catalase glutathione reductase and glutathione peroxidase activities were determined in the liver, heart, kidney, pancreatic tissues and serum samples. Xylitol exhibited significant (p < 0.05) in vitro nitric oxide and hydroxyl radical scavenging and ferric reducing activities. In vivo study revealed significant (p < 0.05) reduction in TBARS concentrations in the xylitol consuming groups compared to their respective controls. Significant (p < 0.05) increase in GSH levels and antioxidant enzyme activities were observed in analyzed tissues and serum of xylitol-fed animals compared to their respective controls. Results of this study indicate that xylitol has strong anti-oxidative potential against T2D-associated oxidative stress. Hence, xylitol can be used as a potential supplement in diabetic foods and food products.

The controlled-environment chamber: a new mouse model of dry eye.

PubMed

Barabino, Stefano; Shen, Linling; Chen, Lu; Rashid, Saadia; Rolando, Maurizio; Dana, M Reza

2005-08-01

To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.

Reduction of intimal hyperplasia and enhanced reactivity of experimental vein bypass grafts with verapamil treatment.

PubMed Central

el-Sanadiki, M N; Cross, K S; Murray, J J; Schuman, R W; Mikat, E; McCann, R L; Hagen, P O

1990-01-01

Recent studies have shown that calcium antagonists exert an antiatherogenic effect in animals fed cholesterol. Vein graft intimal hyperplasia is believed to be an early event in atherosclerotic lesion formation, which is a significant cause of graft failure. Altered vasoreactivity has also been postulated in the etiology of vein graft failure. Therefore this study examined the effect of verapamil treatment on the development of intimal hyperplasia and the vasoreactivity of experimental vein bypass grafts. The right external jugular vein was grafted into the right carotid artery of 30 male New Zealand white rabbits fed normal rabbit chow. The left external jugular vein was used as the control vein. Fifteen animals received verapamil (1.25 mg/day for 28 days) via the femoral vein by means of an osmotic pump. In 15 control animals the pump contained saline. Plasma verapamil concentration was 50.9 +/- 13.2 ng/mL (x +/- SEM), a dose that showed no effect on either blood pressure, total serum cholesterol, or in vitro platelet aggregation to ADP. Fourteen of fifteen grafts were patent in each group, for a patency rate of 93%. Histologic examination using computer morphometry showed significant reduction of intimal hyperplasia at the proximal, middle, and distal graft segments (p less than 0.05). In addition in vitro isometric tension studies of the vein grafts and control veins showed that verapamil causes enhanced reactivity of both vein grafts and control veins in response to norepinephrine and histamine (p less than 0.05). Reactivity of vein grafts to serotonin was unaltered. While none of the normal veins in the control group responded to serotonin, normal veins treated with verapamil contracted readily in response to serotonin. Endothelial-dependent relaxation to acetylcholine was absent in both control and verapamil-treated vein grafts, while normal veins from both groups responded to the same extent to acetylcholine. Because we could not demonstrate any difference in platelet or endothelium function between untreated and verapamil-treated animals, we examined the direct effect of verapamil on smooth muscle. Verapamil significantly inhibited [3H]-thymidine incorporation into DNA in vascular smooth muscle cells in culture in a dose-dependent manner. Verapamil treatment significantly reduces intimal hyperplasia in experimental vein grafts and inhibits smooth muscle cell proliferation in culture. Furthermore the enhanced reactivity to norepinephrine and histamine in the verapamil-treated vessels has no detrimental effect on the patency rate at 4 weeks. Thus by inhibiting intimal hyperplasia, calcium antagonists may improve the long-term patency of vein bypass grafts. Images Figs. 1A-C. PMID:2363608

Meat and milk compositions of bovine clones

PubMed Central

Tian, X. Cindy; Kubota, Chikara; Sakashita, Kunihito; Izaike, Yoshiaki; Okano, Ryoichi; Tabara, Norio; Curchoe, Carol; Jacob, Lavina; Zhang, Yuqin; Smith, Sadie; Bormann, Charles; Xu, Jie; Sato, Masumi; Andrew, Sheila; Yang, Xiangzhong

2005-01-01

The technology is now available for commercial cloning of farm animals for food production, but is the food safe for consumers? Here, we provide data on >100 parameters that compare the composition of meat and milk from beef and dairy cattle derived from cloning to those of genetic- and breed-matched control animals from conventional reproduction. The cloned animals and the comparators were managed under the same conditions and received the same diet. The composition of the meat and milk from the clones were largely not statistically different from those of matched comparators, and all parameters examined were within the normal industry standards or previously reported values. The data generated from our match-controlled experiments provide science-based information desired by regulatory agencies to address public concerns about the safety of meat and milk from somatic animal clones. PMID:15829585

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

PubMed

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

2007-02-01

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

Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats.

PubMed

Al-Obaidi, Mazen M Jamil; Al-Bayaty, Fouad Hussain; Al Batran, Rami; Hussaini, Jamal; Khor, Goot Heah

2014-01-01

To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Twenty-four Sprague Dawley male rats weighing 250-300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction.

Effect of cold and hot ambient temperatures on plasma progesterone concentrations in ewes with intact and denervated ovaries containing experimentally maintained corpora lutea.

PubMed

Wheeler, A G; Blackshaw, A W

1986-11-01

Twenty ewes in which maintained corpora lutea had been established were subject to 1 of 3 treatments: denervation of the ovaries by freezing, denervation of the ovaries using the chemical 6-hydroxydopamine, or control. The animals were exposed sequentially to normal (24.5 degrees C), cold (10.7 degrees C), normal (23.8 degrees C), hot (39.4 degrees C) and normal (24.6 degrees C) temperatures, each for 1 week. On the final 3 days of exposure rectal temperatures and heart rates were measured, and on the final day the body weights, respiratory rates, and blood glucose concentrations were measured and a series of 5 blood samples was collected from each ewe for determination of the progesterone concentrations. The progesterone concentration was greatest during the hot period in 8 of the 12 animals, particularly in the ewes with denervated ovaries (6 of the 7 animals). This suggests that high ambient temperatures increase progesterone concentrations non-specifically, and that denervated ovaries are more sensitive to the circulating catecholamines that presumably mediate this effect. The progesterone concentrations were lower (P less than 0.001) in the groups with freezing or chemically denervated ovaries (2.86 and 2.73 ng/ml respectively) than in the control group (3.38 ng/ml), suggesting that the ovarian innervation plays a physiological role in regulating progesterone secretion.

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

PubMed

Leong, S K

1980-08-04

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

Relationships among neuroscore, magnetic resonance imaging features, and intracranial pressure in sheep affected by slow-growing brain lesions.

PubMed

Evangelisti, Maria A; Deiana, Roberta; Melosu, Valentino; Burrai, Giovanni P; Ballocco, Isabella; Varcasia, Antonio; Scala, Antonio; Manunta, Maria L

2018-05-01

Diagnosing high intracranial pressure by clinical and diagnostic imaging is particularly challenging for chronic or slow-growing lesions. The aim of this prospective case-control study is to determine whether the neuroscore and brain magnetic resonance imaging (MRI) are related to the direct measurement of intracranial pressure in sheep affected by intracranial slow-growing lesions due to chronic cerebral coenurosis (Coenurus cerebralis). Seventeen affected and 10 control sheep were included. All animals underwent a neurological examination, MRI of the brain, and direct measurement of intracranial pressure. The severity of clinical signs and MRI findings were scored. Data were statistically analyzed. The invasive intracranial pressure value was higher in affected animals. A severely altered neuroscore is related to an increased intracranial pressure beyond the normal threshold (P < 0.05). The volume of the calvarium was larger in affected animals than in control animals (P = 0.0001) and was positively influenced by the presence and volume of the parasitic cyst (r = 0.7881, P < 0.01). Several degrees of deviation and deformation of both the ventricular system and brain parenchyma were detected by MRI. Subjective MRI findings were not associated with intracranial hypertension. In conclusion, this study shows that in sheep affected by slow-growing lesions, severe alterations in the neuroscore and the results of objective MRI are related to an increased intracranial pressure beyond the normal threshold. © 2017 American College of Veterinary Radiology.

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

PubMed

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

2011-12-01

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

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

PubMed

Harvie, Michelle; Howell, Anthony

2017-01-19

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

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

PubMed Central

Harvie, Michelle; Howell, Anthony

2017-01-01

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

Similarities and Differences for Swimming in Larval and Adult Lampreys.

PubMed

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

2016-01-01

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

Bilateral neurotoxic amygdala lesions in rhesus monkeys (Macaca mulatta): Consistent pattern of behavior across different social contexts

PubMed Central

Machado, Christopher J.; Emery, Nathan J.; Capitanio, John P.; Mason, William A.; Mendoza, Sally P.; Amaral, David G.

2010-01-01

Although the amygdala has been repeatedly implicated in normal primate social behavior, great variability exists in the specific social and nonsocial behavioral changes observed after bilateral amygdala lesions in nonhuman primates. One plausible explanation pertains to differences in social context. To investigate this idea, we measured the social behavior of amygdala-lesioned and unoperated rhesus monkeys (Macaca mulatta) in two contexts. Animals interacted in four-member social groups over 32 test days. These animals were previously assessed in pairs (Emery et al., 2001), and were, therefore, familiar with each other at the beginning of this study. Across the two contexts, amygdala lesions produced a highly consistent pattern of social behavior. Operated animals engaged in more affiliative social interactions with control group partners than did control animals. In the course of their interactions, amygdala-lesioned animals also displayed an earlier decrease in nervous and fearful personality qualities than controls. The increased exploration and sexual behavior recorded for amygdala-lesioned animals in pairs was not found in the four-member groups. We conclude that the amygdala contributes to social inhibition and this function transcends various social contexts. PMID:18410164

Investigation of electroacupuncture and manual acupuncture on carnitine and glutathione in muscle.

PubMed

Toda, Shizuo

2011-01-01

Electroacupuncture (EA) and manual acupuncture (MA) have therapeutic effects on muscle fatigue in muscle disease. The deficiencies of carnitine and glutathione induce muscle fatigue. This report investigated the effects of EA and MA on carnitine and glutathione in muscle. After the mice of EA group were fixed in the animal cage, right Zusanli (ST36) and Jiexi (ST41) were acupunctured and stimulated with uniform reinforcing and reducing method by twirling the acupuncture needle for 15 min. And then, the needle handles were connected to an electric stimulator for stimulating the acupoint with dense-sparse waves. After the mice of MA group were fixed in an animal cage, right ST36 and ST41 were acupunctured and allowed for 15 min. The mice of normal control group were not acupunctured and stimulated for 15 min. The mice of all groups were killed for collecting muscle tissue 1 h after the final treatment. Carnitine and glutathione in homogenate of muscle tissue were determined with carnitine (Kainos Laboratories Co., Tokyo, Japan) and glutathione assay kit (Dojin Chemicals Co., Kumamoto, Japan). Carnitine level in muscle tissue of MA group was significantly higher than those of EA group and normal control group. Carnitine level in muscle tissue of EA group was not significantly different from that of normal control group. Glutathione levels in muscle tissue of EA group and MA group were significantly higher than that of normal control group. This report presented that carnitine in muscle is increased by MA, and not increased by EA, and that glutathione in muscle is increased by EA and MA.

Investigation of Electroacupuncture and Manual Acupuncture on Carnitine and Glutathione in Muscle

PubMed Central

Toda, Shizuo

2011-01-01

Electroacupuncture (EA) and manual acupuncture (MA) have therapeutic effects on muscle fatigue in muscle disease. The deficiencies of carnitine and glutathione induce muscle fatigue. This report investigated the effects of EA and MA on carnitine and glutathione in muscle. After the mice of EA group were fixed in the animal cage, right Zusanli (ST36) and Jiexi (ST41) were acupunctured and stimulated with uniform reinforcing and reducing method by twirling the acupuncture needle for 15 min. And then, the needle handles were connected to an electric stimulator for stimulating the acupoint with dense-sparse waves. After the mice of MA group were fixed in an animal cage, right ST36 and ST41 were acupunctured and allowed for 15 min. The mice of normal control group were not acupunctured and stimulated for 15 min. The mice of all groups were killed for collecting muscle tissue 1 h after the final treatment. Carnitine and glutathione in homogenate of muscle tissue were determined with carnitine (Kainos Laboratories Co., Tokyo, Japan) and glutathione assay kit (Dojin Chemicals Co., Kumamoto, Japan). Carnitine level in muscle tissue of MA group was significantly higher than those of EA group and normal control group. Carnitine level in muscle tissue of EA group was not significantly different from that of normal control group. Glutathione levels in muscle tissue of EA group and MA group were significantly higher than that of normal control group. This report presented that carnitine in muscle is increased by MA, and not increased by EA, and that glutathione in muscle is increased by EA and MA. PMID:19592478

Association of Diet With Skin Histological Features in UV-B-Exposed Mice.

PubMed

Bhattacharyya, Tapan K; Hsia, Yvonne; Weeks, David M; Dixon, Tatiana K; Lepe, Jessica; Thomas, J Regan

2017-09-01

Long-term exposure to solar radiation produces deleterious photoaging of the skin. It is not known if diet can influence skin photoaging. To study the influence of a calorie-restricted diet and an obesity diet in mice exposed to long-term UV-B irradiation to assess if there is an association between diet and histopathological response to UV-B irradiation. In this animal model study in an academic setting, the dorsal skin of SKH1 hairless mice receiving normal, calorie-restricted, and obesity diets was exposed to UV-B irradiation 3 times a week for 10 weeks and were compared with corresponding controls. The mice were placed in the following groups, with 8 animals in each group: (1) intact control (C) with regular diet and no UV-B exposure, (2) intact control with UV-B exposure (CR), (3) calorie-restricted diet (CrC), (4) calorie-restricted diet with UV-B exposure (CrR), (5) obesity diet (OC), and (6) obesity diet with UV-B exposure (OR). The experiment was conducted during October through December 2013. Tissue processing and histological analysis were completed in 2016. Histomorphometric analysis was performed on paraffin-embedded skin sections stained by histological and immunohistochemical methods for estimation of epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen I, elastic fibers, fibroblasts, mast cells, dermal cellularity, and adipose layer ratio. Changes in wrinkles were noted. Hairless female mice (age range, 6-8 weeks) were obtained. With a normal diet, changes from UV-B irradiation occurred in epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen I, elastic fibers, fibroblasts, and mast cells, which were modestly influenced by an obesity diet. Calorie restriction influenced the skin in nonirradiated control animals, with higher values for most variables. After UV-B exposure in animals with calorie restriction, epidermal thickness was increased, but other variables were unaffected. Animals receiving the calorie-restricted diet lost weight when exposed to long-term UV-B irradiation. Wrinkles were reduced in the calorie-restricted control group and in UV-B-exposed animals who received the obesity diet. Dietary alterations seem to modify histopathological responses to UV-B exposure in the skin of hairless mice. NA.

[Molecular-genetic basis of regulation of the synthesis of individual types of hemoglobin].

PubMed

Starodub, N F

1980-01-01

The data on the control of ontogenetic hemoglobin type synthesis were analyzed in normal and pathological human and animal organisms. The assumption is made that such control depends on the level of erythroid cell differentiation and erythropoetic factors activity. The latters act as a trigger in switching of qualitative hemoglobin production.

I Vivo Quantitative Ultrasound Imaging and Scatter Assessments.

NASA Astrophysics Data System (ADS)

Lu, Zheng Feng

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

Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

PubMed

Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2007-03-01

Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

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

PubMed

Cecim, M; Kerr, J; Bartke, A

1995-05-01

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

Effects of space flight and IGF-1 on immune function

NASA Astrophysics Data System (ADS)

1999-01-01

We tested the hypothesis that insulin-like growth factor-1 (IGF-1) would ameliorate space flight-induced effects on the immune system. Twelve male, Sprague-Dawley rats, surgically implanted with mini osmotic pumps, were subjected to space flight for 10 days on STS-77. Six rats received 10 mg/kg/day of IGF-1 and 6 rats received saline. Flight animals had a lymphocytopenia and granulocytosis which were reversed by IGF-1. Flight animals had significantly higher corticosterone levels than ground controls but IGF-1 did not impact this stress hormone. Therefore, the reversed granulocytosis did not correlate with serum corticosterone. Space flight and IGF-1 also combined to induce a monocytopenia that was not evident in ground control animals treated with IGF-1 or in animals subjected to space flight but given physiological saline. There was a significant increase in spleen weights in vivarium animals treated with IGF-1, however, this change did not occur in flight animals. We observed reduced agonist-induced lymph node cell proliferation by cells from flight animals compared to ground controls. The reduced proliferation was not augmented by IGF-1 treatment. There was enhanced secretion of TNF, IL-6 and NO by flight-animal peritoneal macrophages compared to vivarium controls, however, O2- secretion was not affected. These data suggest that IGF-1 can ameliorate some of the effects of space flight but that space flight can also impact the normal response to IGF-1.

Oxidative stress in normal and diabetic rats.

PubMed

Torres, M D; Canal, J R; Pérez, C

1999-01-01

Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (p<0.001) greater than the control levels. The diabetic animals presented an amount of vitamin E far greater (p<0.0001) than the controls, as was also the case for the vitaminE/polyunsaturated fatty acid (PUFA) and vitaminE/linoleic acid (C18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

Experiment K-6-16. Morphological examination of rat testes. The effect of Cosmos 1887 flight on spermatogonial population and testosterone level in rat testes

NASA Technical Reports Server (NTRS)

Philpott, D. E.; Kato, K.; Stevenson, J.; Vasques, M.; Sapp, W.; Williams, C.; Popova, I. A.; Serova, L. V.

1990-01-01

Testes from rats flown on Cosmos 1887 for twelve and a half days were compared to basal control, synchronous control and vivarium maintained rats. When the mean weights of flight testes, normalized for weight/100 gms, were compared to the vivarium controls they were 6.7 percent lighter. Although the flight testes were lighter than the synchronous, the difference is not significant. Counts of spermatogonial cells from 5 animals in each group revealed a 4 percent decrease in flight compared to vivarium controls. In both cases the t-Test significance was less than 0.02. The serum testosterone levels of all animals (flight, synchronous and vivarium) were significantly below the basal controls.

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

PubMed

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

2014-12-17

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

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

PubMed

Sviderskaia, G E; Dmitrieva, L E

1991-01-01

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

A 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

Estrous Cyclicity in Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Talyansky, Y.; Scott, R. T.; Tash, J. S.; Christenson, L. K.; Alwood, J. S.; Ronca, A. E.

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n=22), normally loaded HU Cage Pair-Fed controls (CPF; n=22), and Vivarium controls fed ad libitum (VIV; n=10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8+/- 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, and/or due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5% vs 3.0%, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system. Research supported by NNX15AB48G to JST.

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

PubMed

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

2012-08-01

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

Radioprotective Effects of Gallic Acid in Mice

PubMed Central

Nair, Gopakumar Gopinathan

2013-01-01

Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control). PMID:24069607

Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation.

PubMed

Rogers, R F; Matzel, L D

1996-01-01

Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.

[Research progress on breeding standard of medicinal animals and discussion on several key problems].

PubMed

Zhou, Yi-Quan; Qu, Xian-You; Yang, Guang; Li, Jun-de; Su, Yan; Li, Ying

2016-12-01

Medicinal animal breeding standards is regarded as the law to normalize relevant production that can guarantee the quality of traditional Chinese medicine of animal category. The article summarized the medicinal animal resources in our country and the present condition of medicinal animal breeding standards. It considered the current animal breeding standards system was in adequate, not only the quantity of breeding standards, the standard content and index were also uncomprehensive, which is not conducive to the scientific and orderly development and utilization of medicinal animal resources. The article pointed out that the development of the basic standards, environmental control, feed quality, raising management, inspection and quarantine should be included into the medicinal animal breeding standards, and the medicinal animal breeding standards content framework was introduced. Meanwhile, animal welfare, biological safety and file management should be concerned during the process of research. Hope the article has good reference value to medicinal animal breeding standards establishment and production management. Copyright© by the Chinese Pharmaceutical Association.

Cerebral utilization of glucose, ketone bodies and oxygen in starving infant rats and the effect of intrauterine growth retardation.

PubMed

Dahlquist, G

1976-10-01

Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate and oxygen and brain DNA content was measured at 20 days of age in intrauterine growth retarded (IUGR) rats and normal littermates after 48 and 72 h of starvation. Cerebral blood flow (CBF) was measured with labeled microspheres in other comparable groups of IUGR and control rats. CBF was similar in IUGR and normal littermates (0.57+/-0.09 and 0.58+/-0.10 ml/min respectively). After 48 h of starvation, arterial glucose was significantly lower in IUGR than control animals but the arterial concentrations of ketone bodies were similar. After 48 h of starvation, cerebral arteriovenous difference of beta-hydroxybutyrate was significantly higher in control than IUGR rats also when expressed per mg brain DNA as was the fractional uptake of D-beta-hydroxybutyrate. After 72 h of starvation, arterial concentrations of ketone bodies were significantly lower in IUGR rats than controls but the fractional uptake of D-beta-hydroxybutyrate was increased compared to IUGR rats starved for 48 h. The average percentage of calculated total substrate uptake (mumol/min) accounted for by ketone bodies increased in control animals from 31.1% after 48 h of starvation to 41.0% after 72 h of starvation. In IUGR rats these percentage values were 26.5 and 25.7 respectively. After 72 h of starvation the fraction of total cerebral uptake of substrates accounted for by ketone bodies was significantly higher in control that IUGR rats. As total cerebral uptake of substrates was similar between IUGR and control animals it is concluded that IUGR rats are more dependent on glucose as a substrate for the brain during starvation.

Analysis of change in gait in the ovine stifle: normal, injured, and anterior cruciate ligament reconstructed.

PubMed

Heard, B J; Beveridge, J E; Atarod, M; O'Brien, E J; Rolian, C; Frank, C B; Hart, D A; Shrive, N G

2017-05-23

Many patients who undergo anterior cruciate ligament (ACL) reconstructive surgery develop post-traumatic osteoarthritis (PTOA). ACL reconstructive surgery may not fully restore pre-injury joint biomechanics, thereby resulting in further joint damage and contributing to the development of PTOA. In an ovine model of idealized ACL reconstruction (ACL-R), it has been shown that signs of PTOA develop within surgical joints by 20 weeks post-surgery. The aim of the present study was to investigate whether altered kinematics contribute to early PTOA development within ACL-R joints of the ovine injury model by comparing the gait of these surgical animals to the gait of a stable normal control group, and an unstable injury group in which the ACL and medial collateral ligament (MCL) had been transected. Fifteen skeletally mature female sheep were allocated evenly into 3 treatment groups: normal control, ACL-R, and ACL/MCL Tx (each group n = 5). Each animal's gait was recorded at baseline, 4 weeks post injury, and 20 weeks post injury. Principal component analysis (PCA) was used to identify the kinematic patterns that may be discriminant between treatment groups. Results from previous studies were referenced to present the amount of gross PTOA-like changes that occurred in the joints. ACL-R and ACL/MCL transected (Tx) animals developed a similar amount of early PTOA-like changes within the surgical joints, but differed significantly in the amount of kinematic change present at 20 weeks post-surgery. We showed that the stifle joint kinematics of ACL/MCL Tx differed significantly from those of CTRL and the majority of ACL-R animals, while no significant differences in joint kinematic changes were found between ACL-R and CTRL animals. These results suggest that the early PTOA-like changes reported in the ACL-R model cannot be attributed exclusively to post-surgical kinematic changes, and therefore biologic components in the post-injury environment must be contributing significantly to PTOA development.

Effects of hypothyroidism on the respiratory system and control of breathing: Human studies and animal models.

PubMed

Schlenker, Evelyn H

2012-04-30

Hypothyroidism, subclinical hypothyroidism and euthyroid sick syndrome, are prevalent disorders that affect all body systems including the respiratory system and control of breathing. The purpose of this review article is to discuss the regulation of thyroid hormone production and their function at the cellular level; the many causes of hypothyroidism; the effects of hypothyroidism on the respiratory system and on control of ventilation in hypothyroid patients; the variety of ways animal models of hypothyroidism are induced; and how in animal models hypothyroidism affects the respiratory system and control of breathing including neurotransmitters that influence breathing. Finally, this review will present controversies that exist in the field and thus encourage new research directions. Because of the high prevalence of hypothyroidism and subclinical forms of hypothyroidism and their influence on ventilation and the respiratory system, understanding underlying molecular mechanisms is necessary to ascertain how and sometimes why not thyroid replacement may normalize function. Copyright © 2012 Elsevier B.V. All rights reserved.

Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane.

PubMed Central

Field, C J; Ryan, E A; Thomson, A B; Clandinin, M T

1988-01-01

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte. PMID:3052424

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

PubMed

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

2018-02-01

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

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

PubMed

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

2017-12-11

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

Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

PubMed Central

Al-Obaidi, Mazen M. Jamil; Al-Bayaty, Fouad Hussain; Hussaini, Jamal; Khor, Goot Heah

2014-01-01

Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction. PMID:25485304

Effects of spaceflight on the spermatogonial population of rat seminiferous epithelium

NASA Technical Reports Server (NTRS)

Sapp, Walter J.; Philpott, Delbert E.; Williams, Carol S.; Kato, Katharine; Stevenson, Joann; Vasquez, M.; Serova, L. V.

1990-01-01

Testes from rats flown on Cosmos 1887 were compared with vivarium control and synchronous control samples. The mean weights of flight testes, normalized for weight per 100 g, were 6.4 percent less when compared with the vivarium controls. Counts of spermatogonia from tissue sections (seminiferous tubules in maturation stage 6) from five animals in each group revealed 4 percent fewer spermatogonia in flight testes compared with synchronous controls and 11 percent fewer spermatogonia in flight samples compared with vivarium controls.

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

PubMed

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

2002-09-01

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

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Developmental hearing loss impedes auditory task learning and performance in gerbils

PubMed Central

von Trapp, Gardiner; Aloni, Ishita; Young, Stephen; Semple, Malcolm N.; Sanes, Dan H.

2016-01-01

The consequences of developmental hearing loss have been reported to include both sensory and cognitive deficits. To investigate these issues in a non-human model, auditory learning and asymptotic psychometric performance were compared between normal hearing (NH) adult gerbils and those reared with conductive hearing loss (CHL). At postnatal day 10, before ear canal opening, gerbil pups underwent bilateral malleus removal to induce a permanent CHL. Both CHL and control animals were trained to approach a water spout upon presentation of a target (Go stimuli), and withhold for foils (Nogo stimuli). To assess the rate of task acquisition and asymptotic performance, animals were tested on an amplitude modulation (AM) rate discrimination task. Behavioral performance was calculated using a signal detection theory framework. Animals reared with developmental CHL displayed a slower rate of task acquisition for AM discrimination task. Slower acquisition was explained by an impaired ability to generalize to newly introduced stimuli, as compared to controls. Measurement of discrimination thresholds across consecutive testing blocks revealed that CHL animals required a greater number of testing sessions to reach asymptotic threshold values, as compared to controls. However, with sufficient training, CHL animals approached control performance. These results indicate that a sensory impediment can delay auditory learning, and increase the risk of poor performance on a temporal task. PMID:27746215

Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.

PubMed

Xu, Huanbin; Andersson, Anne-Marie; Ragonnaud, Emeline; Boilesen, Ditte; Tolver, Anders; Jensen, Benjamin Anderschou Holbech; Blanchard, James L; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Veazey, Ronald S; Holst, Peter Johannes

2017-04-01

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats.

PubMed

Kumar, S Selva; Karrunakaran, C M; Rao, M R K; Balasubramanian, M P

2011-01-11

The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties.

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats

PubMed Central

Kumar, S. Selva; Karrunakaran, C. M.; Rao, M. R. K.; Balasubramanian, M. P.

2011-01-01

Background: The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. Materials and Methods: The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. Results: The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. Conclusion: The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties. PMID:21297921

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

NASA Astrophysics Data System (ADS)

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

2014-05-01

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

Cardiac Energy Metabolism and Oxidative Stress Biomarkers in Diabetic Rat Treated with Resveratrol

PubMed Central

Carolo dos Santos, Klinsmann; Pereira Braga, Camila; Octavio Barbanera, Pedro; Rodrigues Ferreira Seiva, Fábio; Fernandes Junior, Ary; Fernandes, Ana Angélica Henrique

2014-01-01

Resveratrol (RSV), polyphenol from grape, was studied to evaluate its effects on calorimetric parameters, energy metabolism, and antioxidants in the myocardium of diabetic rats. The animals were randomly divided into four groups (n = 8): C (control group): normal rats; C-RSV: normal rats receiving RSV; DM: diabetic rats; and DM-RSV: diabetics rats receiving RSV. Type 1 diabetes mellitus was induced with administration of streptozotocin (STZ; 60 mg−1 body weight, single dose, i.p.). After 48 hours of STZ administration, the animals received RSV (1.0 mg/kg/day) for gavage for 30 days. Food, water, and energy intake were higher in the DM group, while administration of RSV caused decreases (p<0.05) in these parameters. The glycemia decreased and higher final body weight increased in DM-RSV when compared with the DM group. The diabetic rats showed higher serum-free fatty acid, which was normalized with RSV. Oxygen consumption (VO2) and carbon dioxide production (VCO2) decreased (p<0.05) in the DM group. This was accompanied by reductions in RQ. The C-RSV group showed higher VO2 and VCO2 values. Pyruvate dehydrogenase activity was lower in the DM group and normalizes with RSV. The DM group exhibited higher myocardial β-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase activity, and RSV decreased the activity of these enzymes. The DM group had higher cardiac lactate dehydrogenase compared to the DM-RSV group. Myocardial protein carbonyl was increased in the DM group. RSV increased reduced glutathione in the cardiac tissue of diabetic animals. The glutathione reductase activity was higher in the DM-RSV group compared to the DM group. In conclusion, diabetes is accompanied by cardiac energy metabolism dysfunction and change in the biomarkers of oxidative stress. The cardioprotective effect may be mediated through RVS's ability to normalize free fatty acid oxidation, enhance utilization glucose, and control the biomarkers' level of oxidative stress under diabetic conditions. PMID:25050809

Hypoglycemic and antioxidant potential of coconut water in experimental diabetes.

PubMed

Preetha, P P; Devi, V Girija; Rajamohan, T

2012-07-01

Coconut water is a natural nutritious beverage that contains several biologically active compounds. The present study aims to evaluate the hypoglycemic and antioxidant effects of mature coconut water (MCW) on alloxan-induced diabetes in experimental rats. The experimental animals were divided into four groups - normal control, normal rats treated with MCW, diabetic control and diabetic rats treated with MCW. The blood glucose, plasma insulin, hemoglobin, glycated hemoglobin, activities of the various antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase) and lipid peroxidation markers (malondialdehyde, hydroperoxides and conjugated dienes) were evaluated in all the groups. The results indicate that the diabetic animals treated with MCW had decreased blood glucose levels and reduced oxidative stress induced by alloxan, which was evident from the increased activities of the antioxidant enzymes and the decreased levels of the lipid peroxidation products. The overall results indicate that MCW significantly attenuated hyperglycemia and oxidative stress in alloxan-induced diabetic rats, indicating the therapeutic potential of MCW.

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

NASA Technical Reports Server (NTRS)

Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

2012-01-01

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water-selective channel involved in interstitial fluid homeostasis, showed an upregulated trend in HS retinas; however, these results are preliminary. Total retinal thickness increased significantly (P = 0.049) in HS rats fed a resveratrol enriched diet compared to HS rats on a normal diet. This change appeared to be reversed during the 2 weeks of recovery post HS, but no differences in retina thickness were observed between HS animals and HS recovered animals when both groups consumed a normal diet. The reversibility of the increase in retinal thickness induced by resveratrol during HS may therefore reflect an interaction between the stress provoked by HS and the cytoprotective mechanisms elicited by resveratrol

Advanced aging phenotype is revealed by epigenetic modifications in rat liver after in utero malnutrition.

PubMed

Heo, Hye J; Tozour, Jessica N; Delahaye, Fabien; Zhao, Yongmei; Cui, Lingguang; Barzilai, Nir; Einstein, Francine Hughes

2016-10-01

Adverse environmental exposures of mothers during fetal period predispose offspring to a range of age-related diseases earlier in life. Here, we set to determine whether a deregulated epigenetic pattern is similar in young animals whose mothers' nutrition was modulated during fetal growth to that acquired during normal aging in animals. Using a rodent model of maternal undernutrition (UN) or overnutrition (ON), we examined cytosine methylation profiles of liver from young female offspring and compared them to age-matched young controls and aged (20-month-old) animals. HELP-tagging, a genomewide restriction enzyme and sequencing assay demonstrates that fetal exposure to two different maternal diets is associated with nonrandom dysregulation of methylation levels with profiles similar to those seen in normal aging animals and occur in regions mapped to genes relevant to metabolic diseases and aging. Functional consequences were assessed by gene expression at 9 weeks old with more significant changes at 6 months of age. Early developmental exposures to unfavorable maternal diets result in altered methylation profiles and transcriptional dysregulation in Prkcb, Pc, Ncor2, and Smad3 that is also seen with normal aging. These Notch pathway and lipogenesis genes may be useful for prediction of later susceptibility to chronic disease. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

PubMed

Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

2010-08-01

The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

[How to start a neuroimaging study].

PubMed

Narumoto, Jin

2012-06-01

In order to help researchers understand how to start a neuroimaging study, several tips are described in this paper. These include 1) Choice of an imaging modality, 2) Statistical method, and 3) Interpretation of the results. 1) There are several imaging modalities available in clinical research. Advantages and disadvantages of each modality are described. 2) Statistical Parametric Mapping, which is the most common statistical software for neuroimaging analysis, is described in terms of parameter setting in normalization and level of significance. 3) In the discussion section, the region which shows a significant difference between patients and normal controls should be discussed in relation to the neurophysiology of the disease, making reference to previous reports from neuroimaging studies in normal controls, lesion studies and animal studies. A typical pattern of discussion is described.

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

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

PubMed Central

Gentner, G J; Adelmann, B C

1976-01-01

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

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2008-08-01

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

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.

Association of Diet With Skin Histological Features in UV-B–Exposed Mice

PubMed Central

Hsia, Yvonne; Weeks, David M.; Dixon, Tatiana K.; Lepe, Jessica; Thomas, J. Regan

2017-01-01

Importance Long-term exposure to solar radiation produces deleterious photoaging of the skin. It is not known if diet can influence skin photoaging. Objectives To study the influence of a calorie-restricted diet and an obesity diet in mice exposed to long-term UV-B irradiation to assess if there is an association between diet and histopathological response to UV-B irradiation. Design, Setting, and Participants In this animal model study in an academic setting, the dorsal skin of SKH1 hairless mice receiving normal, calorie-restricted, and obesity diets was exposed to UV-B irradiation 3 times a week for 10 weeks and were compared with corresponding controls. The mice were placed in the following groups, with 8 animals in each group: (1) intact control (C) with regular diet and no UV-B exposure, (2) intact control with UV-B exposure (CR), (3) calorie-restricted diet (CrC), (4) calorie-restricted diet with UV-B exposure (CrR), (5) obesity diet (OC), and (6) obesity diet with UV-B exposure (OR). The experiment was conducted during October through December 2013. Tissue processing and histological analysis were completed in 2016. Main Outcomes and Measures Histomorphometric analysis was performed on paraffin-embedded skin sections stained by histological and immunohistochemical methods for estimation of epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen I, elastic fibers, fibroblasts, mast cells, dermal cellularity, and adipose layer ratio. Changes in wrinkles were noted. Results Hairless female mice (age range, 6-8 weeks) were obtained. With a normal diet, changes from UV-B irradiation occurred in epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen I, elastic fibers, fibroblasts, and mast cells, which were modestly influenced by an obesity diet. Calorie restriction influenced the skin in nonirradiated control animals, with higher values for most variables. After UV-B exposure in animals with calorie restriction, epidermal thickness was increased, but other variables were unaffected. Animals receiving the calorie-restricted diet lost weight when exposed to long-term UV-B irradiation. Wrinkles were reduced in the calorie-restricted control group and in UV-B–exposed animals who received the obesity diet. Conclusions and Relevance Dietary alterations seem to modify histopathological responses to UV-B exposure in the skin of hairless mice. Level of Evidence NA. PMID:28418519

Regulatory impairments following selective kainic acid lesions of the neostriatum.

PubMed

Dunnett, S B; Iversen, S D

1980-12-01

Kainic acid lesions were made to the anteromedial (AMC) or ventrolateral (VLC) caudate nucleus and the projection areas of medial and sulcal prefrontal cortex (PFC), respectively. By the second day following lesion, all control and AMC rats had recovered normal food and water intake. By contrast, VLC lesions resulted in severe aphagia and adipsia lasting 3-15 days, accompanied by a rapid loss in weight. Animals were kept alive by palatable food supplement and force-feeding as required. Once all animals had recovered normal food and water intake (3-5 weeks) drinking to various physiological challenges--5% hypertonic saline s.c., food deprivation, quinine adulteration of water and 40% polyethylene glycol--were found to be normal in both lesion groups. By 3 months after lesion the groups did not differ in weight. Acute aphagia and adipsia had been reported following ablation of the sulcal but not the medial PFC in rats. The present experiment obtains parallel results in the PFC projection areas within the neostriatum.

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

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

PubMed

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

2017-09-15

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

Hydrogen in drinking water attenuates noise-induced hearing loss in guinea pigs.

PubMed

Lin, Ying; Kashio, Akinori; Sakamoto, Takashi; Suzukawa, Keigo; Kakigi, Akinobu; Yamasoba, Tatsuya

2011-01-03

It has been shown that molecular hydrogen acts as a therapeutic and preventive antioxidant by selectively reducing the hydroxyl radical, the most cytotoxic of the reactive oxygen species. In the present study, we tested the hypothesis that acoustic damage in guinea pigs can be attenuated by the consumption of molecular hydrogen. Guinea pigs received normal water or hydrogen-rich water for 14 days before they were exposed to 115 dB SPL 4-kHz octave band noise for 3h. Animals in each group underwent measurements for auditory brainstem response (ABR) or distortion-product otoacoustic emissions (DPOAEs) before the treatment (baseline) and immediately, 1, 3, 7, and 14 days after noise exposure. The ABR thresholds at 2 and 4 kHz were significantly better on post-noise days 1, 3, and 14 in hydrogen-treated animals when compared to the normal water-treated controls. Compared to the controls, the hydrogen-treated animals showed greater amplitude of DPOAE input/output growth functions during the recovery process, with statistical significance detected on post-noise days 3 and 7. These findings suggest that hydrogen can facilitate the recovery of hair cell function and attenuate noise-induced temporary hearing loss. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Oxidative/Nitrosative Stress and Protein Damages in Aqueous Humor of Hyperglycemic Rabbits: Effects of Two Oral Antidiabetics, Pioglitazone and Repaglinide

PubMed Central

Gumieniczek, Anna; Owczarek, Beata; Pawlikowska, Bernadeta

2012-01-01

The present study was undertaken to determine oxidative/nitrosative stress in aqueous humor of alloxan-induced hyperglycemic rabbits and to investigate the effects of two oral antidiabetic drugs, pioglitazone from peroxisome proliferator-activated receptor gamma (PPARγ) agonists and repaglinide from nonsulfonylurea KATP channel blockers. Ascorbic acid (AA), glutathione (GSH), total antioxidant status (TAS), lipid peroxidation products (LPO), total nitrites (NO2), advanced oxidized protein products (AOPP), and protein carbonyl groups (PCG) were determined using respective colorimetric and ELISA methods. In our hyperglycemic animals, AA decreased by 77%, GSH by 45%, and TAS by 66% as compared to control animals. Simultaneously, LPO increased by 78%, PCG by 60%, AOPP by 84%, and NO2 by 70%. In pioglitazone-treated animals, AA and TAS increased above control values while GSH and PCG were normalized. In turn, LPO was reduced by 54%, AOPP by 84%, and NO2 by 24%, in relation to hyperglycemic rabbits. With repaglinide, AA and TAS were normalized, GSH increased by 20%, while LPO decreased by 45%. Our results show that pioglitazone and repaglinide differ significantly in their ability to ameliorate the parameters like NO2, PCG, and AOPP. In this area, the multimodal action of pioglitazone as PPARγ agonist is probably essential. PMID:22474428

[Melatonin as a universal stabilizing factor of mental activity].

PubMed

Arushanian, Ē B

2011-01-01

Pineal hormone melatonin stabilizes mental activity of man and animals due to its somnogenic, anxiolytic, antidepressant and nootropic properties. Melatonin effects are based on the synchronization of biological rhythms via the influence on the cerebral structures which control biological rhythms and emotions and normalize endocrine and immune state.

Neuropeptides linking the control of appetite with reproductive function in domestic animals

USDA-ARS?s Scientific Manuscript database

The occurrence of puberty and maintenance of normal reproductive cycles are regulated by secretion of gonadotropin hormones from the pituitary gland, which is dependent upon the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. It is well established that secretion of...

Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats

USDA-ARS?s Scientific Manuscript database

Animals and humans show decrements in motor control, cognition, and brain function during normal aging, partly due to the long-term effects of oxidative stress and inflammation. Recent studies have identified a number of fruits and vegetables, whose phytochemical make-up contains potent antioxidant ...

Copper toxicity in ruminant animals

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

Oehme, F.W.

This discussion includes clinical and post mortem features, metabolism of both normal and toxic quantities of copper, effect of copper upon the tissues, and control treatment and prevention of copper toxicity. These effects are discussed in regard to ruminants. Specific emphasis is placed on metabolism and biochemistry. 33 references, 3 figures.

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

PubMed

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

2013-01-01

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

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

Safety of Microbubbles and Transcranial Ultrasound in Rabbits

NASA Astrophysics Data System (ADS)

Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

2007-05-01

The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.

PubMed

Richardson, William H; Tanen, David A; Tong, Tri C; Betten, David P; Carstairs, Shaun D; Williams, Saralyn R; Cantrell, Frank L; Clark, Richard F

2005-06-01

Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance). A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times. The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study. FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .

Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

PubMed

Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

2013-06-01

The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

PubMed Central

Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan

2013-01-01

Abstract The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity. PMID:23668862

Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading

PubMed Central

Siu, Parco M.; Pistilli, Emidio E.; Alway, Stephen E.

2008-01-01

Oxidative stress increases during unloading in muscle from young adult rats. The present study examined the markers of oxidative stress and antioxidant enzyme gene and protein expressions in medial gastrocnemius muscles of aged and young adult (30 and 6 mo of age) Fischer 344 × Brown Norway rats after 14 days of hindlimb suspension. Medial gastrocnemius muscle weight was decreased by ∼30% in young adult and aged rats following suspension. When muscle weight was normalized to animal body weight, it was reduced by 12% and 22% in young adult and aged rats, respectively, after suspension. Comparisons between young adult and aged control animals demonstrated a 25% and 51% decline in muscle mass when expressed as absolute muscle weight and muscle weight normalized to the animal body weight, respectively. H2O2 content was elevated by 43% while Mn superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended muscles compared with control muscles exclusively in the aged animals. Suspended muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE) (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine (76% and 65% increase in young adult and aged rats, respectively), and catalase activity (69% and 43% increase in young adult and aged rats, respectively) relative to control muscles. Changes in oxidative stress markers MDA/4-HAE, H2O2, and MnSOD protein contents in response to hindlimb unloading occurred in an age-dependent manner. These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia-associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading. PMID:18801960

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

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

Static magnetic field effects on the sagittal suture in Rattus norvegicus.

PubMed

Camilleri, S; McDonald, F

1993-03-01

Twenty-day-old Wistar albino rats were exposed to static magnetic fields by placing a neodymium-iron-boron magnetic over their sagittal suture. Cellular activity was monitored by the uptake of tritiated thymidine in control, north, south, and unoperated animals at 1, 3, 5, and 10 days (n = 10 per group). A total of 160 animals were used for this part of the study, with the animals examined 1, 3, 5, and 10 days after surgery. Bone remodeling was examined by tetracycline fluorescence with 10 animals allocated to 5- and 10-day periods for north and south poles (n = 10 per group) and control experiments. This consisted of the placement of unmagnetized alloy, similar in size and shape to the magnets, and also included unoperated animals (n = 5 per group). A total of 60 animals were used for the tetracycline study and were examined at 5 and 10 days after surgery. While the tetracycline examination revealed very little change, the thymidine reflected a reduction in thymidine uptake subsequent to placement of the magnet, reaching a maximal effect at 3 days and returning to a normal value thereafter. This questions the potential of static magnetic fields affecting cell mitotic activity as previously reported.

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

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

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

1959-04-01

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

Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.

PubMed

Trevisan, Chiara; Montillo, Marta; Prandi, Alberto; Mkupasi, Ernatus M; Ngowi, Helena A; Johansen, Maria V

2017-05-15

The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (p<0.001) in T. solium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Developmental hearing loss impedes auditory task learning and performance in gerbils.

PubMed

von Trapp, Gardiner; Aloni, Ishita; Young, Stephen; Semple, Malcolm N; Sanes, Dan H

2017-04-01

The consequences of developmental hearing loss have been reported to include both sensory and cognitive deficits. To investigate these issues in a non-human model, auditory learning and asymptotic psychometric performance were compared between normal hearing (NH) adult gerbils and those reared with conductive hearing loss (CHL). At postnatal day 10, before ear canal opening, gerbil pups underwent bilateral malleus removal to induce a permanent CHL. Both CHL and control animals were trained to approach a water spout upon presentation of a target (Go stimuli), and withhold for foils (Nogo stimuli). To assess the rate of task acquisition and asymptotic performance, animals were tested on an amplitude modulation (AM) rate discrimination task. Behavioral performance was calculated using a signal detection theory framework. Animals reared with developmental CHL displayed a slower rate of task acquisition for AM discrimination task. Slower acquisition was explained by an impaired ability to generalize to newly introduced stimuli, as compared to controls. Measurement of discrimination thresholds across consecutive testing blocks revealed that CHL animals required a greater number of testing sessions to reach asymptotic threshold values, as compared to controls. However, with sufficient training, CHL animals approached control performance. These results indicate that a sensory impediment can delay auditory learning, and increase the risk of poor performance on a temporal task. Copyright © 2016 Elsevier B.V. All rights reserved.

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

Assessing the effect of immunosuppression on engraftment of pancreatic islets

PubMed Central

Vallabhajosyula, Prashanth; Hirakata, Atsushi; Shimizu, Akira; Okumi, Masayoshi; Tchipashvili, Vaja; Hong, Hanzhou; Yamada, Kazuhiko; Sachs, David H.

2013-01-01

Objective In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets following allogeneic islet cell transplantation. Using our previously described islet-kidney transplantation model in miniature swine, we studied whether an islet toxic triple-drug immunosuppressive regimen (cyclosporine + azathioprine + prednisone) affects the islet engraftment process and thus long-term islet function. Design and Methods Donor animals underwent partial pancreatectomy, autologous islet preparation and injection of these islets under the autologous kidney capsule to prepare an islet-kidney (IK). Experimental animals received daily triple drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to eight weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of ~ 4500 islet equivalents (IE)/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term. Results Diabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control (n=3) and the experimental (n=4) arms of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, > 3 months post-IK transplant showed essentially equivalent glycemic control in both control and experimental animals. Conclusion In this pre-clinical, in vivo large animal model of islet transplantation, the effect of triple drug immunosuppression on islet function does not negatively affect islet engraftment, as assessed by the long-term function of engrafted islets. PMID:23883972

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

Possible carcinogenic potential of dimethyl dimethoxy biphenyl dicarboxylate in experimental animals

PubMed Central

Botros, Sanaa Sabet; El-Lakkany, Naglaa Mohamed; Hammam, Olfat Ali; Sabra, Abdel-Naser Abdel-Aal; Taha, Alaa Awad

2016-01-01

Dimethyl dimethoxy biphenyl dicarboxylate (DDB) has been extensively used in the treatment of liver diseases accounting for 1–6% of the global disease burden. Cell replication, DNA synthesis, and proliferation, providing significant information about behavior of cells were examined in mice exposed to subchronic administration with DDB. Conventional liver functions specifically gamma-glutamyltransferase (γ-GT), a marker expressing liver canceration was also investigated. Normal mice were allocated into two groups each of 10 mice. The 1st and 2nd groups were treated with DDB in a dose of 50 mg/kg/day, 5 days/week for 1 month and 3 months, respectively. Comparable groups of normal mice were left without treatment as controls. Compared to normal control group, animals receiving DDB for 3 months showed marked elevations of both alanine aminotransferase and γ-GT, significant inhibition in cytochrome P450, a significant increase in the mean ploidy and 4C with moderate to marked increase in S-phase populations and the number of proliferating cell nuclear antigen-positive cells. In conclusion, this is the first report on the potential relationship between the subchronic administration of DDB and the increase in the hepatocyte proliferation, cell replication and DNA synthesis that may raise an alarm regarding possible DDB insult on the biological behavior of cells. PMID:27144153

The Effects of Panax ginseng and Panax quinquefolius on Thermoregulation in Animal Models

PubMed Central

Hong, Bin Na; Do, Moon Ho; Her, You Ri

2015-01-01

We devised a study using animal models of hyperthermia and hypothermia and also attempted to accurately assess the effects of Panax ginseng (PG) and Panax quinquefolius (PQ) on body temperature using these models. In addition, we investigated the effects of PG and PQ in our animal models in high and low temperature environments. The results of our experiments show that mice with normothermia, hyperthermia, and hypothermia maintained their body temperatures after a certain period in accordance with the condition of each animal model. In our experiments of body temperature change in models of normal, low, or high room temperature, the hyperthermic model did not show any body temperature change in either the PG- or PQ-administered group. In the normal and low room temperature models, the group administered PG maintained body temperature, while the body temperature of the PQ-administered group was lower than or similar to that of the control group. In conclusion, the fact that PG increases body temperature could not be verified until now. We also showed that the effect of maintaining body temperature in the PG-administered group was superior in a hypothermia-prone low temperature environment. PMID:25709709

Sleep-wake responses of squirrel monkeys exposed to hyperdynamic environments

NASA Technical Reports Server (NTRS)

Fuller, C. A.

1983-01-01

This study examines the sleep responses of primates to acute 3 Gz environments. To investigate this question, loosely-restrained squirrel monkeys were exposed to 70 minutes of 3 Gz during the day. The animals' behavioral state was polygraphically monitored (EEG, EMG, EOG) along with video and deep body temperature. During the control period, animals exhibited slow wave sleep (SWS) napping behavior. SWS occurred during approximately 20 percent of the control period. Body temperature was maintained at 38.7 C. At 3 Gz, SWS was inhibited for 5 minutes, after which SWS occurred at levels 50 percent lower than in the control period. During the post-centrifugation period, SWS was elevated above the control (50 percent) and hyperdynamic (100 percent) levels. Body temperature was depressed 1.5 C when the animals were at 3 Gz. Thus, hyperdynamic environments are capable of modifying primate sleep behavior, at least as a result of acute exposure. Further, the increased arousal in the hyperdynamic environment is correlated with a lower body temperature. This negative correlation differs from the normal positive correlation of arousal and body temperature.

Reduced tear production in three canine endocrinopathies.

PubMed

Williams, D L; Pierce, V; Mellor, P; Heath, M F

2007-05-01

Previous reports have suggested that hypothyroid and diabetic patients can be predisposed to keratoconjunctivitis sicca. This study aimed to measure tear production in dogs with diabetes, hypothyroidism and hyperadrenocorticism using the Schirmer tear test and to compare these results with Schirmer tear test values for a group of normal dogs. Schirmer tear tests were performed on 16 dogs with hyperadrenocorticism, 18 with diabetes and 12 with hypothyroidism together with 100 control dogs. Corneal sensitivity was also measured in 12 of the 18 diabetic dogs with a Cochet Bonnet aesthesiometer and compared with age- and breed-matched normal dogs. Schirmer tear test values in dogs with hypothyroidism, hyperadrenocorticism and diabetes were 12.3+/-3.2, 14.0+/-4.0 and 12.3+/-5.3 mm/minutes, respectively. Schirmer tear test values were significantly lower than that for the control group (19.6+/-4.2 mm/minutes) in all dogs with an endocrinopathy. Only in two hypothyroid dogs and three diabetics, this was manifested as profound keratoconjunctivitis sicca with Schirmer tear test value lower than 5 mm/minutes. Diabetic dogs had significantly reduced corneal sensitivity compared with a matched set of control dogs. This study shows a significant reduction in tear production in animals with diabetes mellitus, hypothyroidism and hyperadrenocorticism. Further research is needed to elucidate the mechanisms by which this reduction in tear production occurs. Assessment of tear production should be undertaken in animals diagnosed with these endocrinopathies, as these animals may progress to clinical keratoconjunctivitis sicca.

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

Che, Magnus M.; Conti, Michele; Chanda, Soma

We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarinmore » exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.« less

Ethanol extract of the leaves of Psidium guajava Linn enhances sperm output in healthy Wistar rats.

PubMed

Akinola, O B; Oladosu, O S; Dosumu, O O

2007-06-01

Reactive oxygen species (ROS), among other factors, have been implicated in the aetiology of male infertility. Thus, the roles of antioxidants at improving sperm production and quality are being investigated. The present study was designed to assess the effect of the ethanol extract of fresh leaves of Psidium guajava Linn. on the sperm parameters of healthy male Wistar rats. A total of 18 rats, weighing between 108-124 g, were divided into 3 groups of 6 animals each. Animals in groups 1 and 2 were administered 250 mg/kg/d and 500 mg/kg/d of guava leaf extract (GLE) orally for 53 days respectively. Group 3 animals received normal saline. Sperm count increased from 56.2+/-0.3 (x10(6)) in the control to 57.1+/-0.2 (x10(6)) in group 1 animals, and from 56.2+/-0.3 (x10(6)) in the control to 72.3+/-0.4 (x10(6)) in group 2 animals. Similarly, dose-dependent increases in the percentages of motile spermatozoa were observed in GLE-treated animals compared to the control group. These findings suggest that the extracts of the leaves of Psidium guajava Linn. possess beneficial effects on sperm production and quality, and may thus improve the sperm parameters of infertile males with oligospermia and nonobstructive azoospermia.

Study of Methylene Blue Ototoxicity in the Guinea Pig.

PubMed

Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam

2017-11-01

Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field.

Study of Methylene Blue Ototoxicity in the Guinea Pig

PubMed Central

Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam

2017-01-01

Background Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. Methods It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. Results The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. Conclusion In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field. PMID:29038666

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

PubMed Central

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-01-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.—Sun, D., Nakao, S., Xie, F., Zandi, S., Bagheri, A., Kanavi, M. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

Use of the multifocal electroretinogram (mfERG) for assessing the response of 670 nm light emitting diodes (LED) photoillumination in an animal model with laser retinal injuries

NASA Astrophysics Data System (ADS)

DiCarlo, Cheryl D.; Brown, Jeremiah; Grado, Andres; Sankovich, James; Zwick, Harry; Lund, David J.; Stuck, Bruce E.

2004-07-01

There is no uniformly accepted objective method to diagnose the functional extent of retinal damage following laser eye injury and there is no uniform therapy for laser retinal injury. J.T. Eells, et al, reported the use of Light Emitting Diodes (LED) photoillumination (670 nm) for methanol-induced retinal toxicity in rats. The findings indicated a preservation of retinal architecture, as determined by histopathology and a partial functional recovery of photoreceptors, as determined by electroretinogram (ERG), in the LED exposed methanol-intoxicated rats. The purpose of this study is to use multifocal electroretinography (mfERG) to evaluate recovery of retinal function following treatment with LED photoillumination in a cynomolgus monkey laser retinal injury model. Control and LED array (670 nm) illuminated animals received macular Argon laser lesions (514 nm, 130 mW, 100 ms). LED array exposure was accomplished for 4 days for a total dose of 4 J/cm2 per day. Baseline and post-laser exposure mfERGs were performed. mfERG results for five animals post-laser injury but prior to treatment (Day 0) showed increased implicit times and P1 waveform amplitudes when compared to a combined laboratory normal and each animal's baseline normal values. In general, preliminary mfERG results of our first five subjects recorded using both the 103-hexagon and 509-hexagon patterns indicate a more rapid functional recovery in the LED illuminated animal as compared to the control by the end of the fourth day post-exposure. Research is continuing to determine if this difference in functional return is seen in additional subjects and if statistical significance exists.

Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

PubMed

Aoyama, Naoki; Katayama, Yoichi; Kawamata, Tatsuro; Maeda, Takeshi; Mori, Tatsuro; Yamamoto, Takamitsu; Kikuchi, Tetsuro; Uwahodo, Yasuhumi

2002-05-03

In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.

The last common ancestor of animals lacked the HIF pathway and respired in low-oxygen environments

PubMed Central

Vargas, Sergio; Larsen, Morten; Elemans, Coen PH; Canfield, Donald E

2018-01-01

Animals have a carefully orchestrated relationship with oxygen. When exposed to low environmental oxygen concentrations, and during periods of increased energy expenditure, animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery, and by enabling the anaerobic production of ATP. These low-oxygen responses are thought to be controlled universally across animals by the hypoxia-inducible factor (HIF). We find, however, that sponge and ctenophore genomes lack key components of the HIF pathway. Since sponges and ctenophores are likely sister to all remaining animal phyla, the last common ancestor of extant animals likely lacked the HIF pathway as well. Laboratory experiments show that the marine sponge Tethya wilhelma maintains normal transcription under oxygen levels down to 0.25% of modern atmospheric saturation, the lowest levels we investigated, consistent with the predicted absence of HIF or any other HIF-like pathway. Thus, the last common ancestor of all living animals could have metabolized aerobically under very low environmental oxygen concentrations. PMID:29402379

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

Effects of tretinoin on wound healing in aged skin.

PubMed

de Campos Peseto, Danielle; Carmona, Erica Vilaça; Silva, Kellyn Cristina da; Guedes, Flavia Roberta Valente; Hummel Filho, Fernando; Martinez, Natalia Peres; Pereira, José Aires; Rocha, Thalita; Priolli, Denise Gonçalves

2016-03-01

Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid-Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing. © 2016 by the Wound Healing Society.

40 CFR 798.3300 - Oncogenicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... that survival in all groups does not fall below 50 percent at the time of termination. (2) Control... test comprise the majority of the normal life span of the strain of animals to be used. This time... 30 months for rats and 24 months for mice. For longer time periods, and where any other species are...

40 CFR 798.3300 - Oncogenicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that survival in all groups does not fall below 50 percent at the time of termination. (2) Control... test comprise the majority of the normal life span of the strain of animals to be used. This time... 30 months for rats and 24 months for mice. For longer time periods, and where any other species are...

40 CFR 798.3300 - Oncogenicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... that survival in all groups does not fall below 50 percent at the time of termination. (2) Control... test comprise the majority of the normal life span of the strain of animals to be used. This time... 30 months for rats and 24 months for mice. For longer time periods, and where any other species are...

40 CFR 798.3300 - Oncogenicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... that survival in all groups does not fall below 50 percent at the time of termination. (2) Control... test comprise the majority of the normal life span of the strain of animals to be used. This time... 30 months for rats and 24 months for mice. For longer time periods, and where any other species are...

40 CFR 798.3300 - Oncogenicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... that survival in all groups does not fall below 50 percent at the time of termination. (2) Control... test comprise the majority of the normal life span of the strain of animals to be used. This time... 30 months for rats and 24 months for mice. For longer time periods, and where any other species are...

Motion sickness elicited by passive rotation in squirrel monkeys

NASA Technical Reports Server (NTRS)

Daunton, Nancy G.; Fox, Robert A.

1991-01-01

Current theory and recent evidence suggest that motion sickness occurs under conditions of sensory input in which the normal motor programs for producing eye, head, and body movements are not functionally effective, i.e. under conditions in which there are difficulties in maintaining posture and controlling eye movements. Conditions involving conflicting or inconsistent visual-vestibular (VV) stimulation should thus result in greater sickness rates since the existing motor programs do not produce effective control of eye-head-body movements under such conditions. It is felt that the relationship of postural control to motion sickness is an important one and one often overlooked. The results are reported which showed that when postural requirements were minimized by fully restraining squirrel monkeys during hypogravity parabolic flight, no animals became motion sick, but over 80 percent of the same 11 animals became sick if they were unrestrained and maintained control of their posture.

Endotracheal aerosolization of atropine sulfate protects against soman-induced acute respiratory toxicity in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Song, Jian; Marshall, Seema; Oguntayo, Samuel; Morthole, Venee; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2011-03-01

The efficacy of endotracheal aerosolization of atropine sulfate for protection against soman (GD)-induced respiratory toxicity was investigated using microinstillation technique in guinea pigs. GD (841 mg/m(3), 1.3 LCt(50) or 1121 mg/m(3), 1.7 LCt(50)) was aerosolized endotracheally to anesthetized male guinea pigs that were treated with atropine sulfate (5.0 mg/kg) 30 s postexposure by endotracheal microinstillation. Animals exposed to 841 mg/m(3) and 1121 mg/m(3)GD resulted in 31 and 13% while treatment with atropine sulfate resulted in 100 and 50% survival, respectively. Cholinergic symptoms and increased body weight loss were reduced in atropine-treated animals compared to GD controls. Diminished pulse rate and blood O(2) saturation in GD-exposed animals returned to normal levels after atropine treatment. Increased cell death, total cell count and protein in the bronchoalveolar fluid (BALF) in GD-exposed animals returned to normal levels following atropine treatment. GD exposure increased glutathione and superoxide dismutase levels in BALF and that were reduced in animals treated with atropine. Respiratory parameters measured by whole-body barometric plethysmography revealed that treatment with atropine sulfate resulted in normalization of respiratory frequency, tidal volume, time of expiration, time of inspiration, end expiratory pause, pseudo lung resistance (Penh) and pause at 4 and 24 h post 841 mg/m(3) GD exposure. Lung histopathology showed that atropine treatment reduced bronchial epithelial subepithelial inflammation and multifocal alveolar septal edema. These results suggest that endotracheal aerosolization of atropine sulfate protects against respiratory toxicity and lung injury induced by microinstillation inhalation exposure to lethal doses of GD.

Reward value-based gain control: divisive normalization in parietal cortex.

PubMed

Louie, Kenway; Grattan, Lauren E; Glimcher, Paul W

2011-07-20

The representation of value is a critical component of decision making. Rational choice theory assumes that options are assigned absolute values, independent of the value or existence of other alternatives. However, context-dependent choice behavior in both animals and humans violates this assumption, suggesting that biological decision processes rely on comparative evaluation. Here we show that neurons in the monkey lateral intraparietal cortex encode a relative form of saccadic value, explicitly dependent on the values of the other available alternatives. Analogous to extra-classical receptive field effects in visual cortex, this relative representation incorporates target values outside the response field and is observed in both stimulus-driven activity and baseline firing rates. This context-dependent modulation is precisely described by divisive normalization, indicating that this standard form of sensory gain control may be a general mechanism of cortical computation. Such normalization in decision circuits effectively implements an adaptive gain control for value coding and provides a possible mechanistic basis for behavioral context-dependent violations of rationality.

Added sugars and risk factors for obesity, diabetes and heart disease.

PubMed

Rippe, J M; Angelopoulos, T J

2016-03-01

The effects of added sugars on various chronic conditions are highly controversial. Some investigators have argued that added sugars increase the risk of obesity, diabetes and cardiovascular disease. However, few randomized controlled trials are available to support these assertions. The literature is further complicated by animal studies, as well as studies which compare pure fructose to pure glucose (neither of which is consumed to any appreciable degree in the human diet) and studies where large doses of added sugars beyond normal levels of human consumption have been administered. Various scientific and public health organizations have offered disparate recommendations for upper limits of added sugar. In this article, we will review recent randomized controlled trials and prospective cohort studies. We conclude that the normal added sugars in the human diet (for example, sucrose, high-fructose corn syrup and isoglucose) when consumed within the normal range of normal human consumption or substituted isoenergetically for other carbohydrates, do not appear to cause a unique risk of obesity, diabetes or cardiovascular disease.

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

PubMed

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

2016-12-01

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

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

PubMed Central

Ishiguro, Akio; Trimmer, Barry A.

2016-01-01

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

Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal male rats.

PubMed

Suresh, Sekar; Prithiviraj, Elumalai; Prakash, Seppan

2009-04-21

According to Indian Systems of Medicine, Mucuna pruriens Linn., belonging to the leguminous family (Papilionaceae), were used for treating male sexual disorders since ancient times. In this study, the effects of ethanolic extracts of the Mucuna pruriens Linn. seed on general mating behaviour, libido and potency of normal male Wister albino rats were investigated and also compared with the standard reference drug, Sildenafil citrate. Animals were divided into one control group (Group I--received saline) and four experimental groups (Groups II-V). Experimental groups were divided on the basis of the dosage of extract to the animals as follows: 150 mg/kg body weight (Group I), 200mg/kg body weight (Group II) and 250 mg/kg body weight (Group IV) while Group V received Sildenafil citrate (5mg/kg body weight). Animals were fed PO with saline or extract or standard drug once in a day for 45 days. To analyse the mating behaviour, female rats with oestrus phase were used. The extract administered PO significantly increased the mounting frequency, intromission frequency and ejaculation latency, and decreased the mounting latency, intromission latency, post-ejaculatory interval and inter-intromission interval. The potency test significantly increased erections, quick flips, long flips and total reflex. Therefore, the results indicated that the ethanolic extracts of Mucuna pruriens Linn. seed produced a significant and sustained increase in the sexual activity of normal male rats at a particular dose (200mg/kg). When compared to control, all the drug-treated groups have shown drug-induced effects for a few parameters. However in Group II, there was an obvious enhancement in all parameters, without affecting the normal behaviour. When compared with the standard drug, the net effect of extract is even less than that in Group II. Therefore, the resulting aphrodisiac activity of the extract lends support to the claim that it has traditionally been used for the treatment of sexual disorders.

Recovery of wild Pacific oyster, Crassostrea gigas in terms of reproduction and gametogenesis two-years after the Hebei Spirit Oil Spill Accident off the West Coast of Korea

NASA Astrophysics Data System (ADS)

Mondol, Mostafizur Rahman; Keshavmurthy, Shashank; Lee, Hee-Jung; Hong, Hyun-Ki; Park, Heung-Sik; Park, Sang-Rul; Kang, Chang-Keun; Choi, Kwang-Sik

2015-12-01

The Hebei Spirit oil spill in December 2007 at Taean off the west coast of Korea was the largest oil tanker accident in Korea. However, the impact of the spill on physiology of benthic animals remains largely unknown. Two-years after the accident, we compared reproductive effort and annual gametogenesis of the wild Pacific oyster Crassostrea gigas, residing at oil spill site with a control oyster population in Incheon Bay, North-West coast of Korea. Results showed that the oyster sampled from the oil spill site showed a significantly higher (279.0 mg standard animal-1, P<0.05) growth by tissue dry weight to that of the control population (228.0 mg standard animal-1, P<0.05). Histology revealed that there was no significant difference in the annual gametogenic pattern between the two populations, and most of the females of both populations spawned between August and September. During spawning season, egg mass of oysters determined using enzyme-linked immunosorbant assay (ELISA) in the oil spill area was significantly higher (136.3 mg standard animal-1, P<0.05) than the control population (120.5 mg standard animal-1, P<0.05). The tissue protein level in the oysters at the contaminated area was significantly higher (102.6 mg standard animal-1, P<0.05) than the level measured from the control oysters (81.4 mg standard animal-1, P<0.05). The observed better biological performances of oysters at the contaminated site suggested their recovery of the physiological status to normal level after two years of the oil spill accident.

[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.

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

PubMed Central

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

2014-01-01

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

The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe.

PubMed

Chassagne, M; Barnouin, J

1993-04-01

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe.

The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe.

PubMed Central

Chassagne, M; Barnouin, J

1993-01-01

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe. PMID:8490813

Vasopressin infusion into the lateral septum of adult male rats rescues progesterone induced impairment in social recognition

PubMed Central

Bychowski, Meaghan E.; Mena, Jesus D.; Auger, Catherine J.

2013-01-01

It is well established that social recognition memory is mediated, in part, by arginine vasopressin (AVP). AVP cells within the bed nucleus of the stria terminalis (BST) and medial amygdala (MeA) send AVP-ergic projections to the lateral septum (LS). We have demonstrated that progesterone treatment decreases AVP immunoreactivity within the BST, the MeA and the LS, and that progesterone treatment impairs social recognition. These data suggested that progesterone may impair social recognition memory by decreasing AVP. In the present experiment, we hypothesized that infusions of AVP into the LS would rescue the progesterone induced impairment in social recognition within adult male rats. One week after adult male rats underwent cannula surgery, they were given systemic injections of either a physiological dose of progesterone or oil control for three days. Four hours after the last injection, we tested social recognition memory using the social discrimination paradigm, a two-trial test that is based on the natural propensity for rats to be highly motivated to investigate novel conspecifics. Immediately after the first exposure to a juvenile, each animal received bilateral infusions of either AVP or artificial CSF (aCSF) into the LS. Our results show that, as expected, control animals exhibited normal social discrimination. In corroboration with our previous results, animals given progesterone have impaired social discrimination. Interestingly, animals treated with progesterone and AVP exhibited normal social discrimination, suggesting that AVP treatment rescued the impairment in social recognition caused by progesterone. These data also further support a role for progesterone in modulating vasopressin dependent behavior within the male brain. PMID:23639881

Spermatoprotective activity of the leaf extract of Psidium guajava Linn.

PubMed

Akinola, O B; Oladosu, O S; Dosumu, O O

2007-12-01

The leaves of Psidium guajava Linn. (guava) contain several natural antioxidants. We therefore designed the present study to evaluate the effect of ethanol extract of guava leaves on gossypol-associated sperm toxicity in Wistar rats. Animal groups 1, 2, and 3 (n=6 each) were treated orally with crude cottonseed oil to provide 14 mg/kg/d of free gossypol for 53 d. Besides, groups 1 and 2 rats were supplemented orally with 250 mg/kg/d and 500 mg/kg/d respectively of guava leaf extract (GLE) for the same period. Group 4 animals (control, n=6) received normal saline. No significant difference (P>0.05) occurred in the sperm count of group 1 rats compared to control. In animal group 2, significant increase (P<0.05) in sperm count occurred, as opposed to group 3 animals, where this parameter decreased significantly (P<0.05). Besides, mean values of 78 %, 82 %, 30 %, and 65 % respectively were obtained for sperm motility in animal groups 1, 2, 3, and 4. Our findings suggest that ethanol extract of guava leaves possesses beneficial effect on gossypol-associated sperm toxicity, and may therefore enhance male fertility, possibly owing to its rich constituents of natural antioxidants.

[Muscle regeneration in mdx mouse, and a trial of normal myoblast transfer into regenerating dystrophic muscle].

PubMed

Takemitsu, M; Arahata, K; Nonaka, I

1990-10-01

The most ideal therapeutic trial on Duchenne muscular dystrophy (DMD) is a transfer of normal myoblasts into dystrophic muscle which has been attempted on animal models in several institutes. In the process of muscle regeneration, the transferred normal myoblasts are expected to incorporate into the regenerating fibers in host dystrophic mouse. To know the capacity of muscle regeneration in dystrophic muscle, we compared the regenerating process of the normal muscle with that of the dystrophic muscle after myonecrosis induced by 0.25% bupivacaine hydrochloride (BPVC) chronologically. In the present study, C57BL/10ScSn-mdx (mdx) mouse was used as an animal model of DMD and C57BL/10ScSn (B10) mouse as a control. There was no definite difference in the behavior of muscle fiber regeneration between normal and dystrophic muscles. The dystrophic muscle regenerated rapidly at the similar tempo to the normal as to their size and fiber type differentiation. The variation in fiber size diameter of dystrophic muscle, however, was more obvious than that of normal. To promote successful myoblast transfer from B10 mouse into dystrophic mdx mouse at higher ratio, cultured normal myoblasts were transferred into the regenerating dystrophic muscle on the first and the second day after myonecrosis induced by BPVC. Two weeks after the myoblast injection, the muscles were examined with immunohistochemical stain using anti dystrophin antibody. Although dystrophin-positive fibers appeared in dystrophic muscle, the positive fibers were unexpectedly small in number (3.86 +/- 1.50%).(ABSTRACT TRUNCATED AT 250 WORDS)

Childhood pet ownership, attachment to pets, and subsequent meat avoidance. The mediating role of empathy toward animals.

PubMed

Rothgerber, Hank; Mican, Frances

2014-08-01

Researchers studying childhood pet ownership outcomes do not typically focus on measures of adult diet, and those studying the psychology of meat consumption do not normally consider early experiences with companion animals. The present research sought to integrate these two areas by examining relationships between childhood pet ownership, pet attachment, empathy toward animals, belief in human-animal similarity, meat avoidance, and justifications for eating meat. Results from 273 individuals responding to a survey on an internet platform revealed that participants with greater childhood attachment to a pet reported greater meat avoidance as adults, an effect that disappeared when controlling for animal empathy. Greater childhood pet attachment was also related to the use of indirect, apologetic justifications for meat consumption, and this effect too, was mediated by empathy toward animals. Child pet ownership itself predicted views toward animals but not dietary behavior or meat-eating justifications. The authors propose a sequence of events by which greater childhood pet attachment leads to increased meat avoidance, focusing on the central role played by empathy toward animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia

PubMed Central

Okoye, B.; Losty, P.; Fisher, M.; Wilmott, I.; Lloyd, D.

1998-01-01

AIMS—To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH).
METHODS—CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry.
RESULTS—On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups.
CONCLUSIONS—eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.

 PMID:9713033

The effect of acid drinking water on rumen protozoa in the blesbok (Damaliscus dorcas phillipsi).

PubMed

Booyse, D G; Dehority, B A; Myburgh, J G

2015-12-07

Rumen contents were collected from ten adult female blesbok, five from a mine area with only acid drinking water available and five from a control group consuming normal, non-polluted drinking water. The mean concentration of total protozoa in the normal water group was almost double that in the acid drinking water group, 24.9 x 10(3) versus 14.7 x 10(3). Percent of Entodinium was higher and Diplodinium lower in those animals drinking the acid water. The number of different protozoa species present in animals from both locations was fairly similar. Diplodinium bubalidis, Ostracodinium gracile and Diplodinium consors were present in the highest percentage in the normal water group, 18.8, 18.4 and 17.7 %, respectively. The same three species, plus Entodinium dubardi, were also highest in the acid water group, O. gracile, 21.3 %; D. consors, 12.6 %; E. dubardi, 11.4 % and D. bubalidis, 10.3 %. Seventeen species of protozoa found in this study were a new host record for the blesbok, bringing the total number of species reported from the blesbok to 29.

Mouse brain responses to charged particle radiation

NASA Astrophysics Data System (ADS)

Nelson, Gregory; Nelson, Gregory; Chang, Polly; Favre, Cecile; Fike, John; Mao, Xiao-Wen; Obenaus, Andre; Pecaut, Michael; Vlkolinsky, Roman; Song, Sheng-Kwei; Spigelman, Igor; Stampanoni, Marco

CHANGES IN DISEASE LATENCY AND HOMEOSTASIS: 1) APP23 transgenic mice exhibit many of the pathological features of Alzheimer's Disease, and the disease progression is continuous over several months. Electrophysiological measurements have shown that disease-related decreases in synaptic efficacy occur earlier in irradiated APP23 animals. 2) Using vascular polymer cast technology combined with micro-tomographic imaging, microvasculature changes following irradiation have been detected and are consistent with loss of vessels and an increased spacing between them. The time course of vessel changes to control and irradiated animals is being constructed. 3) In order to assess the ability of the brain to respond to external environmental shocks and restore orderly normal function (homeostasis), we apply a controlled septic shock by treating animals with lipopolysaccharide (LPS). We find that in irradiated animals, the patterns of electrophysiological changes associated with reactions to lipopolysaccharide (LPS) are complex and unlike those of either LPS or irradiation alone. They further suggest that the brain continues to remodel for up to 6 months following radiation. This is consistent with the idea that irradiation may potentiate the risks from late secondary insults.

Theoretical and practical considerations in the application of whole body plethysmography to sleep research.

PubMed

Stephenson, Richard; Gucciardi, Enza J

2002-07-01

The sleep-wake state has a profound influence on many, perhaps most, aspects of normal physiology and is strongly implicated in the mediation (or remediation) of impaired health and performance. Many sleep disorders stem from abnormal respiratory anatomy or sleep-induced changes in respiratory control, underscoring the need for research into the effects of the sleep-wake state on respiratory control processes. Whole body plethysmography is being increasingly used to study respiration in freely behaving animals, and is especially well suited to studies of sleeping animals and human subjects. The method is simple in principle, but care is required in its application to ensure reliable results, and there are circumstances in which it is an inappropriate technique. This review describes the main advantages, pitfalls, and limitations inherent in the use of whole body plethysmography for non-invasive measurement of lung ventilation and metabolic rate in sleeping animals. Sources of potential error, and ways of avoiding such errors, are discussed, with reference to studies involving animal models of sleep-related breathing disorders.

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

PubMed

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

2015-08-01

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

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

PubMed

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

2005-07-01

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

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.

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.

The effects of lesions of the superior colliculus on locomotor orientation and the orienting reflex in the rat.

PubMed

Goodale, M A; Murison, R C

1975-05-02

The effects of bilateral removal of the superior colliculus or visual cortex on visually guided locomotor movements in rats performing a brightness discrimination task were investigated directly with the use of cine film. Rats with collicular lesions showed patterns of locomotion comparable to or more efficient than those of normal animals when approaching one of 5 small doors located at one end of a large open area. In contrast, animals with large but incomplete lesions of visual cortex were distinctly impaired in their visual control of approach responses to the same stimuli. On the other hand, rats with collicular damage showed no orienting reflex or evidence of distraction in the same task when novel visual or auditory stimuli were presented. However, both normal and visual-decorticate rats showed various components of the orienting reflex and disturbance in task performance when the same novel stimuli were presented. These results suggest that although the superior colliculus does not appear to be essential to the visual control of locomotor orientation, this midbrain structure might participate in the mediation of shifts in visual fixation and attention. Visual cortex, while contributing to visuospatial guidance of locomotor movements, might not play a significant role in the control and integration of the orienting reflex.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats.

PubMed

Tuzcu, Zeynep; Orhan, Cemal; Sahin, Nurhan; Juturu, Vijaya; Sahin, Kazim

2017-01-01

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR- α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile ( P < 0.05) and reduced serum and liver MDA concentration compared to HFD rats ( P < 0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR- α , ACLY, FAS, and NF- κ B p65 expressions and enhanced the PPAR- α , IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers ( P < 0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

PubMed Central

Tuzcu, Zeynep; Orhan, Cemal; Sahin, Nurhan; Juturu, Vijaya

2017-01-01

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P < 0.05) and reduced serum and liver MDA concentration compared to HFD rats (P < 0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P < 0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver. PMID:28396714

Lipidemic effects of common edible oils and risk of atherosclerosis in diabetic Wistar rats

PubMed Central

Oladapo, Olulola Olutoyin; Ojora, Kehinde Adeyemi; Quadri, Oluwafemi Majeed; Ajani, Rotimi Sunday

2017-01-01

BACKGROUND Diabetic state potentiates atherosclerosis and the type of edible oil consumed by the individual may affect this further. This study aimed to determine if the common edible oils in Nigeria have any effects on the lipid profiles and arteries of alloxan-induced diabetic male Wistar rats. METHODS Thirty male Wistar rats were randomly divided into five groups of normal control, diabetic control, animals on diet enriched with refined, bleached deodorized palm oil (RBD-PO), animals on diet enriched with soya oil, and animals on diet enriched with olive oil. At the end of 8 weeks, the lipid profiles of the animals were determined before sacrificing them. Their aortas were subsequently harvested for histological examination. RESULTS The olive oil fed group had the highest level of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), lowest HDL-C, and highest artherogenic index (AI). Diabetic animals fed on RBD-PO had a lower non-HDL-C, higher HDL-C, and lower AI than diabetic animals fed on olive oil or soya oil. However, the diabetic animals fed on RBD-PO had the highest triglyceride level. When the aortas were examined histologically, there were no atherosclerotic lesions in all the control and experimental groups except those fed on 10% soya oil enriched diet that had type II atherosclerotic lesions according to American Heart Association (AHA). CONCLUSION The result of our study showed that RBD-PO appears to offer a better lipid profile in the diabetic animals compared with olive oil and soya oil. Soya oil appears to cause the development of atherosclerosis in diabetic state. PMID:28761450

Low body temperature in long-lived Ames dwarf mice at rest and during stress.

PubMed

Hunter, W S; Croson, W B; Bartke, A; Gentry, M V; Meliska, C J

1999-09-01

Among homeothermic animals, larger species generally have lower metabolic rates and live longer than do smaller species. Because Ames dwarf mice (dwarfs) live approximately 1 year longer than their larger normal sex- and age-matched siblings (normals), we hypothesized that they would have lower body core temperature (Tco). We, therefore, measured Tco of six dwarfs and six normals during 24-h periods of ad lib feeding, 24-h food deprivation, and emotional stress induced by cage switching. With ad lib feeding, Tco of dwarfs averaged 1.6 degrees C lower than normals; during food deprivation, Tco of both dwarfs and controls was significantly lower than when food was available ad lib; and following cage switch, Tco was elevated in both groups. However, during all three experiments, Tco was significantly lower in dwarfs than in normals. These data support the hypothesis that Ames dwarf mice, which live longer than normal size controls, maintain lower Tco than normals. Because dwarfs are deficient in thyroid stimulating hormone (TSH) and growth hormone (GH), their low Tco may be a result of reduced thermogenesis due to lack of those hormones. However, whether low Tco per se is related to the increased longevity of the dwarf mice remains an interesting possibility to be investigated.

ICG: a wiki-driven knowledgebase of internal control genes for RT-qPCR normalization.

PubMed

Sang, Jian; Wang, Zhennan; Li, Man; Cao, Jiabao; Niu, Guangyi; Xia, Lin; Zou, Dong; Wang, Fan; Xu, Xingjian; Han, Xiaojiao; Fan, Jinqi; Yang, Ye; Zuo, Wanzhu; Zhang, Yang; Zhao, Wenming; Bao, Yiming; Xiao, Jingfa; Hu, Songnian; Hao, Lili; Zhang, Zhang

2018-01-04

Real-time quantitative PCR (RT-qPCR) has become a widely used method for accurate expression profiling of targeted mRNA and ncRNA. Selection of appropriate internal control genes for RT-qPCR normalization is an elementary prerequisite for reliable expression measurement. Here, we present ICG (http://icg.big.ac.cn), a wiki-driven knowledgebase for community curation of experimentally validated internal control genes as well as their associated experimental conditions. Unlike extant related databases that focus on qPCR primers in model organisms (mainly human and mouse), ICG features harnessing collective intelligence in community integration of internal control genes for a variety of species. Specifically, it integrates a comprehensive collection of more than 750 internal control genes for 73 animals, 115 plants, 12 fungi and 9 bacteria, and incorporates detailed information on recommended application scenarios corresponding to specific experimental conditions, which, collectively, are of great help for researchers to adopt appropriate internal control genes for their own experiments. Taken together, ICG serves as a publicly editable and open-content encyclopaedia of internal control genes and accordingly bears broad utility for reliable RT-qPCR normalization and gene expression characterization in both model and non-model organisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Gastroprotective Properties of Karanjin from Karanja (Pongamia pinnata) Seeds; Role as Antioxidant and H, K-ATPase Inhibitor.

PubMed

Vismaya; Belagihally, Srikanta M; Rajashekhar, Sindhu; Jayaram, Vinay B; Dharmesh, Shylaja M; Thirumakudalu, Sindhu Kanya C

2011-01-01

Plant extracts are the most attractive sources of newer drugs and have been shown to produce promising results for the treatment of gastric ulcers. Karanjin, a furano-flavonoid has been evaluated for anti-ulcerogenic property by employing adult male albino rats. Karanjin (>95% pure) was administered to these rats in two different concentrations, that is, 10 and 20 mg kg(-1) b.w. Ulcers were induced in the experimental animals by swim and ethanol stress. Serum, stomach and liver-tissue homogenates were assessed for biochemical parameters. Karanjin inhibited 50 and 74% of ulcers induced by swim stress at 10 and 20 mg kg(-1) b.w., respectively. Gastric mucin was protected up to 85% in case of swim stress, whereas only 47% mucin recovery was seen in ethanol stress induced ulcers. H(+), K(+)-ATPase activity, which was increased 2-fold in ulcer conditions, was normalized by Karanjin in both swim/ethanol stress-induced ulcer models. Karanjin could inhibit oxidative stress as evidenced by the normalization of lipid peroxidation and antioxidant enzyme (i.e., catalase, peroxidase and superoxide dismutase) levels. Karanjin at concentrations of 20 mg kg(-1) b.w., when administered orally for 14 days, did not indicate any lethal effects. There were no significant differences in total protein, serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase between normal and Karanjin-treated rats indicating no adverse effect on major organs. During treatment schedule, animals remained as healthy as control animals with normal food and water intake and body weight gain.

Gastroprotective Properties of Karanjin from Karanja (Pongamia pinnata) Seeds; Role as Antioxidant and H+, K+-ATPase Inhibitor

PubMed Central

Vismaya; Belagihally, Srikanta M.; Rajashekhar, Sindhu; Jayaram, Vinay B.; Dharmesh, Shylaja M.; Thirumakudalu, Sindhu Kanya C.

2011-01-01

Plant extracts are the most attractive sources of newer drugs and have been shown to produce promising results for the treatment of gastric ulcers. Karanjin, a furano-flavonoid has been evaluated for anti-ulcerogenic property by employing adult male albino rats. Karanjin (>95% pure) was administered to these rats in two different concentrations, that is, 10 and 20 mg kg−1 b.w. Ulcers were induced in the experimental animals by swim and ethanol stress. Serum, stomach and liver-tissue homogenates were assessed for biochemical parameters. Karanjin inhibited 50 and 74% of ulcers induced by swim stress at 10 and 20 mg kg−1 b.w., respectively. Gastric mucin was protected up to 85% in case of swim stress, whereas only 47% mucin recovery was seen in ethanol stress induced ulcers. H+, K+-ATPase activity, which was increased 2-fold in ulcer conditions, was normalized by Karanjin in both swim/ethanol stress-induced ulcer models. Karanjin could inhibit oxidative stress as evidenced by the normalization of lipid peroxidation and antioxidant enzyme (i.e., catalase, peroxidase and superoxide dismutase) levels. Karanjin at concentrations of 20 mg kg−1 b.w., when administered orally for 14 days, did not indicate any lethal effects. There were no significant differences in total protein, serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase between normal and Karanjin-treated rats indicating no adverse effect on major organs. During treatment schedule, animals remained as healthy as control animals with normal food and water intake and body weight gain. PMID:21799691

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

PubMed

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

1998-02-01

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

Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats.

PubMed Central

Neuwelt, E A; Johnson, W G; Blank, N K; Pagel, M A; Maslen-McClure, C; McClure, M J; Wu, P M

1985-01-01

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model. Images PMID:4040927

Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats.

PubMed

Neuwelt, E A; Johnson, W G; Blank, N K; Pagel, M A; Maslen-McClure, C; McClure, M J; Wu, P M

1985-08-01

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model.

Effects of simulated increased gravity on the rate of aging of rats - Implications for the rate of living theory of aging

NASA Technical Reports Server (NTRS)

Economos, A. C.; Ballard, R. C.; Blunden, M.; Miquel, J.; Lindseth, K. A.; Fleming, J.; Philpott, D. E.; Oyama, J.

1982-01-01

It was found that the rate of aging of 17 month old rats which had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 months was larger than that of the controls as determined by the apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration. Steady-state food intake per day per kg body weight, which is presumably proportional to rate of living or specific basal metabolic expenditure, was found to be about 18 percent higher than in the controls after an initial 2 month adaptation period. Although half of the centrifuged animals lived only a little shorter than the controls (average about 343 vs. 364 days on the average, statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for the controls, computed from the onset of centrifugation, or 11 percent shorter. These findings indicate that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's (1928) rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

[The thyroid gland in emotional and pain stress].

PubMed

Akhmetov, I Z

1987-01-01

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

Proanthocyanidin-Rich Grape Seed Extract Modulates Intestinal Microbiota in Ovariectomized Mice.

PubMed

Jin, Guangwen; Asou, Yoshinori; Ishiyama, Kirika; Okawa, Atsushi; Kanno, Taro; Niwano, Yoshimi

2018-04-01

Grape-seed extract (GSE) is rich in proanthocyanidins (polymers of flavan-3-ols). GSE is well known to have various beneficial effects to health. The objective of this study was to examine the effect of dietary GSE on the intestinal microbiota in ovariectomized (OVX) mice as a model of menopause. Phylum-level analyses using 16S rRNA-targeted group-specific polymerase-chain reaction primers in fecal samples collected 8 weeks postoperatively from OVX mice revealed that the proportion of Firmicutes and Bacteroidetes populations became imbalanced as compared with that in sham-operated control mice. That is, the ratio of Firmicutes:Bacteroidetes populations in the OVX group were increased significantly. When OVX animals were given dietary GSE, the imbalanced proportion of Firmicutes and Bacteroidetes populations was normalized to that seen in control mice. In addition, the body weight of OVX animals measured at 6 weeks postoperatively was significantly higher than that in sham-operated control animals. Dietary GSE also prevented OVX animals from increasing body weight. Thus, we postulated that GSE can improve imbalanced populations of intestinal microbiota, leading to prevention of obesity under conditions of not only menopause but morbidity. The GSE has a great potential to be a functional food to improve dysbiosis in post-menopausal women. © 2018 Institute of Food Technologists®.

The sensory but not muscular pelvic nerve branch is necessary for parturition in the rat.

PubMed

Martínez-Gómez, M; Cruz, Y; Pacheco, P; Aguilar-Roblero, R; Hudson, R

1998-03-01

In the rat the pelvic nerve consists of a viscerocutaneous (sensory) branch which receives information from pelvic viscera and the midline perineal region, and a somatomotor (muscular) branch which innervates the ilio- and pubococcygeous muscles. To investigate the contribution of these branches to the parturition process, the length of gestation and course of delivery were closely monitored in 43 pregnant, Wistar-strain rats randomly assigned to five groups: untreated control animals, animals in which the somatomotor branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals in which the viscerocutaneous branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals treated similarly to the previous group but with young delivered by C-section at term, and sham-operated controls. Sectioning the viscerocutaneous branch seriously disrupted parturition and resulted in major dystocia and a high percentage of stillbirths in all females. In contrast, sectioning the somatomotor branch had no apparent effect on parturition and no significant differences were found between females of this group and sham or control dams on any of the measures recorded. It is concluded that the viscerocutaneous branch of the pelvic nerve is vital for the normal course of parturition in the rat but that the somatomotor branch plays little role, if any.

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

PubMed

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

2005-01-01

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

Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanosoma cruzi.

PubMed

Basso, B; Moretti, E; Fretes, R

2014-01-15

Chagas' disease, endemic in Latin America, is spread in natural environments through animal reservoirs, including marsupials, mice and guinea pigs. Farms breeding guinea pigs for food are located in some Latin-American countries with consequent risk of digestive infection. The aim of this work was to study the effect of vaccination with Trypanosoma rangeli in guinea pigs challenged with Trypanosoma cruzi. Animals were vaccinated with fixated epimastigotes of T. rangeli, emulsified with saponin. Controls received only PBS. Before being challenged with T. cruzi, parasitemia, survival rates and histological studies were performed. The vaccinated guinea pigs revealed significantly lower parasitemia than controls (p<0.0001-0.01) and a discrete lymphomonocytic infiltrate in cardiac and skeletal muscles was present. In the chronic phase, the histological view was normal. In contrast, control group revealed amastigote nests and typical histopathological alterations compatible with chagasic myocarditis, endocarditis and pericarditis. These results, together with previous works in our laboratory, show that T. rangeli induces immunoprotection in three species of animals: mice, guinea pigs and dogs. The development of vaccines for use in animals, like domestic dogs and guinea pigs in captivity, opens up new opportunities for preventive tools, and could reduce the risk of infection with T. cruzi in the community. Copyright © 2013 Elsevier B.V. All rights reserved.

Sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats is related with fetal programming of insulin and leptin resistance.

PubMed

Palou, Mariona; Priego, Teresa; Sánchez, Juana; Palou, Andreu; Picó, Catalina

2010-08-26

We aimed to characterize the lasting effect of moderate caloric restriction during early pregnancy on offspring energy homeostasis, by focusing on the effects on food intake and body weight as well as on the insulin and leptin systems. Male and female offspring of 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied. These animals were fed after weaning with a normal-fat (NF) diet until the age of 4 months, and then moved to a high-fat (HF) diet. Blood parameters were measured under fed and 14-h fasting conditions at different ages (2, 4 and 5 months). Food preferences were also assessed in adult animals. Accumulated caloric intake from weaning to the age of 5 months was higher in CR animals compared with their controls, and this resulted in higher body weight in adulthood in males, but not in females. Both male and female CR animals already showed higher insulin levels at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of 4 months, compared with their controls. CR male animals, but not females, displayed higher preference for fat-rich food than their controls in adulthood and higher circulating leptin levels when they were under HF diet. It is suggested that hyperinsulinemia may play a role in the etiology of hyperphagia in the offspring of caloric restricted animals during gestation, with different outcomes on body weight depending on the gender, which could be associated with different programming effects on later leptin resistance.

Sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats is related with fetal programming of insulin and leptin resistance

PubMed Central

2010-01-01

Aim We aimed to characterize the lasting effect of moderate caloric restriction during early pregnancy on offspring energy homeostasis, by focusing on the effects on food intake and body weight as well as on the insulin and leptin systems. Methods Male and female offspring of 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied. These animals were fed after weaning with a normal-fat (NF) diet until the age of 4 months, and then moved to a high-fat (HF) diet. Blood parameters were measured under fed and 14-h fasting conditions at different ages (2, 4 and 5 months). Food preferences were also assessed in adult animals. Results Accumulated caloric intake from weaning to the age of 5 months was higher in CR animals compared with their controls, and this resulted in higher body weight in adulthood in males, but not in females. Both male and female CR animals already showed higher insulin levels at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of 4 months, compared with their controls. CR male animals, but not females, displayed higher preference for fat-rich food than their controls in adulthood and higher circulating leptin levels when they were under HF diet. Conclusion It is suggested that hyperinsulinemia may play a role in the etiology of hyperphagia in the offspring of caloric restricted animals during gestation, with different outcomes on body weight depending on the gender, which could be associated with different programming effects on later leptin resistance. PMID:20796266

Aging of Cloned Animals: A Mini-Review.

PubMed

Burgstaller, Jörg Patrick; Brem, Gottfried

2017-01-01

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

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

NASA Technical Reports Server (NTRS)

Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

2003-01-01

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat

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

Wilson, B.W.; Anderson, L.E.; Hilton, D.I.

As a component of studies to search for effects of 60-Hz electric field exposure on mammalian endocrine function, concentrations of melatonin, 5-methoxytryptophol, and serotonin-N-acetyl transferase activity were measured in the pineal glands of rats exposed or sham-exposed at 65 kV/m for 30 days.In two replicate experiments there were statistically significant differences between exposed and control rats in that the normal nocturnal increase in pineal melatonin content was depressed in the exposed animals. Concentrations of 5-methoxytryptophol were increased in the pineal glands of the exposed groups when compared to sham-exposed controls. An alteration was also observed in serotonin-N-acetyl transferase activity, withmore » lower levels measured in pineal glands from exposed animals.« less

Retropatellar chondromalacia associated with medial osteoarthritis after meniscus injury. One year of observations in sheep.

PubMed

Burger, C; Kabir, K; Mueller, M; Rangger, C; Minor, T; Tolba, R H

2006-01-01

In an ovine meniscal repair model, the patellofemoral (PF) osteoarthritis due to a non-sutured tear or failed repair was investigated. A radial meniscus tear was either sutured with polydioxanone (PDS), with a slow degrading polylactide long-term suture(LTS) or left without treatment. Knee joint cartilage in the PF and medial compartment was evaluated compared to normal knees (healthy controls). Retropatellar osteoarthritis in the non-sutured and sutured animals was intense in contrast to the control knees after 6 months in all groups (p < 0.001), and after 12 months in the PDS group (p < 0.001), LTS group and non-sutured animals (p < 0.05). Non-sutured meniscus tears and failed repair lead fast to intense PF osteoarthritis corresponding with tibial damage of the injured compartment.

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.

PubMed Central

Tisdale, M. J.; Brennan, R. A.

1988-01-01

A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size. PMID:3219268

Schedule-induced polydipsia: a rat model of obsessive-compulsive disorder.

PubMed

Platt, Brian; Beyer, Chad E; Schechter, Lee E; Rosenzweig-Lipson, Sharon

2008-04-01

Obsessive-compulsive disorder (OCD) is difficult to model in animals due to the involvement of both mental (obsessions) and physical (compulsions) symptoms. Due to limitations of using animals to evaluate obsessions, OCD models are limited to evaluation of the compulsive and repetitive behaviors of animals. Of these, models of adjunctive behaviors offer the most value in regard to predicting efficacy of anti-OCD drugs in the clinic. Adjunctive behaviors are those that are maintained indirectly by the variables that control another behavior, rather than directly by their own typical controlling variables. Schedule-induced polydipsia (SIP) is an adjunctive model in which rats exhibit exaggerated drinking behavior (polydipsia) when presented with food pellets under a fixed-time schedule. The polydipsic response is an excessive manifestation of a normal behavior (drinking), providing face validity to the model. Furthermore, clinically effective drugs for the treatment of OCD decrease SIP. This protocol describes a rat SIP model of OCD and provides preclinical data for drugs that decrease polydipsia and are clinically effective in the treatment of OCD.

Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

PubMed Central

Fazleabas, A. T.; Braundmeier, A. G.; Markham, R.; Fraser, I. S.; Berbic, M.

2011-01-01

Mounting evidence suggests that immunological responses may be altered in endometriosis. The baboon (Papio anubis) is generally considered the best model of endometriosis pathogenesis. The objective of the current study was to investigate for the first time immunological changes within uterine and peritoneal draining lymph nodes in a nonhuman primate baboon model of endometriosis. Paraffin-embedded femoral lymph nodes were obtained from 22 normally cycling female baboons (induced endometriosis n = 11; control n = 11). Immunohistochemical staining was performed with antibodies for endometrial stromal cells, T cells, immature and mature dendritic cells, and B cells. Lymph nodes were evaluated using an automated cellular imaging system. Endometrial stromal cells were significantly increased in lymph nodes from animals with induced endometriosis, compared to control animals (P = .033). In animals with induced endometriosis, some lymph node immune cell populations including T cells, dendritic cells and B cells were increased, suggesting an efficient early response or peritoneal drainage. PMID:21617251

Companion Animal Death.

PubMed

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

2017-06-01

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

Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats

PubMed Central

Selvamani, Amutha; Sohrabji, Farida

2009-01-01

While human observational studies and animal studies report a neuroprotective role for estrogen therapy in stroke, the multicenter placebo-controlled Women's Health Initiative (WHI) study concluded that hormone therapy increased the risk for stroke in postmenopausal women. The present study therefore tested the hypothesis that estrogen replacement would increase the severity of a stroke-like injury in females when this replacement occurs after a prolonged hypoestrogenic period, such as the menopause or reproductive senescence, but not when given to females that were normally cycling immediately prior to the hormone replacement. Two groups of female rats were used: multiparous females with normal but lengthened estrus cycles (mature adults), and older multiparous females currently in a persistent acyclic state (reproductive senescent). Animals were either used intact, or were bilaterally ovariectomized and immediately replaced with a 17β-estradiol pellet or control pellet. Animals were subject to a forelimb placing test (a test for sensorimotor deficit) and thereafter to middle cerebral artery occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were performed again. Cortical and striatal infarct volume, measured from brain slices, was significantly greater in intact reproductive senescent females as compared to intact mature adults. Furthermore, estrogen treatment to ovariectomized mature adult females significantly reduced the cortical infarct volume. Paradoxically, estrogen treatment to ovariectomized reproductive senescent females significantly increased cortical and striatal infarct volumes as compared to control pellet replaced senescent females. Significant post-stroke behavioral deficit was observed in all groups on the side contralateral to the lesion, while senescent females also exhibited deficits on the ipsilateral side, in the cross-midline forelimb placement test. Using an animal model that approximates the natural ovarian aging process, these findings strongly support the hypothesis that the effectiveness of estrogen therapy in protecting brain health may depend critically on the time of initiation with respect to a female's reproductive status. PMID:18829137

Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer.

PubMed

Kalayci, Mehmet; Kocdor, Mehmet Ali; Kuloglu, Tuncay; Sahin, İbrahim; Sarac, Mehmet; Aksoy, Aziz; Yardim, Meltem; Dalkilic, Semih; Gursu, Onur; Aydin, Suna; Akkoc, Ramazan Fazil; Ugras, Meltem; Artas, Gokhan; Ozercan, İbrahim Hanifi; Ugur, Kader; Aydin, Suleyman

2017-10-01

The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer+NS); Group III (5mg/kg sildenafil citrate, low dose); Group IV (10mg/kg sildenafil citrate, high dose); Group V (0.6mg/kg heparin, low dose); Group VI (6mg/kg heparin, high dose); Group VII (20nmol/kg des-acyl ghrelin); Group VIII (40nmol/kg des-acyl ghrelin); Group IX (4nmol/kg acyl ghrelin); Group X (8nmol/kg acly ghrelin); Group XI (20pmol/kg Nesfatin-1); Group XII (15nmol/kg Obestatin) and Group XIII (5nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-06-01

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

Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo

PubMed Central

Hrgovic, Igor; Glavic, Zeljko; Kovacic, Zeljko; Mulic, Smaila; Zunic, Lejla; Hrgovic, Zlatko

2014-01-01

ABSTRACT Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. Results: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options. PMID:24937925

Resistance to antibiotics in the normal flora of animals.

PubMed

Sørum, H; Sunde, M

2001-01-01

The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans.

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

Estrogens and development

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

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

1987-11-01

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

Plasma butyrylcholinesterase regulates ghrelin to control aggression

PubMed Central

Chen, Vicky Ping; Gao, Yang; Geng, Liyi; Parks, Robin J.; Pang, Yuan-Ping; Brimijoin, Stephen

2015-01-01

Ongoing mouse studies of a proposed therapy for cocaine abuse based on viral gene transfer of butyrylcholinesterase (BChE) mutated for accelerated cocaine hydrolysis have yielded surprising effects on aggression. Further investigation has linked these effects to a reduction in circulating ghrelin, driven by BChE at levels ∼100-fold above normal. Tests with human BChE showed ready ghrelin hydrolysis at physiologic concentrations, and multiple low-mass molecular dynamics simulations revealed that ghrelin’s first five residues fit sterically and electrostatically into BChE’s active site. Consistent with in vitro results, male BALB/c mice with high plasma BChE after gene transfer exhibited sharply reduced plasma ghrelin. Unexpectedly, such animals fought less, both spontaneously and in a resident/intruder provocation model. One mutant BChE was found to be deficient in ghrelin hydrolysis. BALB/c mice transduced with this variant retained normal plasma ghrelin levels and did not differ from untreated controls in the aggression model. In contrast, C57BL/6 mice with BChE gene deletion exhibited increased ghrelin and fought more readily than wild-type animals. Collectively, these findings indicate that BChE-catalyzed ghrelin hydrolysis influences mouse aggression and social stress, with potential implications for humans. PMID:25646463

Simulated weightlessness - Effects on bioenergetic balance

NASA Technical Reports Server (NTRS)

Jordan, J. P.; Sykes, H. A.; Crownover, J. C.; Schatte, C. L.; Simmons, J. B., II; Jordan, D. P.

1980-01-01

As a prelude to a flight experiment, an attempt was made to separate energy requirements associated with gravity from all other metabolic needs. The biological effects of weightlessness were simulated by suspending animals in a harness so that antigravity muscles were not supporting the body. Twelve pairs of rats were allowed to adapt to wearing a harness for 5 d. Experimental animals were then suspended in harness for 7 d followed by recovery for 7 d. Control animals were harnessed but never suspended. Oxygen consumption, carbon dioxide production and rate of (C-14)O2 expiration from radio-labeled glucose were monitored on selected days. Food intake and body mass were recorded daily. Metabolic rate decreased in experimental animals during 7 d of suspension and returned to normal during recovery. Although some of the metabolic changes may have related to variation in food intake, simulated weightlessness appears to directly affect bioenergetic balance.

Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure.

PubMed

Theus, S A; Tabor, D R; Soderberg, L S; Barnett, J B

1992-09-01

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

PubMed

Molinari, Ana J; Thorp, Silvia I; Portu, Agustina M; Saint Martin, Gisela; Pozzi, Emiliano C C; Heber, Elisa M; Bortolussi, Silva; Itoiz, Maria E; Aromando, Romina F; Monti Hughes, Andrea; Garabalino, Marcela A; Altieri, Saverio; Trivillin, Verónica A; Schwint, Amanda E

2015-01-01

We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.

PubMed

Holubova, Kristina; Kleteckova, Lenka; Skurlova, Martina; Ricny, Jan; Stuchlik, Ales; Vales, Karel

2016-06-01

The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus. Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.

Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol.

PubMed

Gabriel, Kara I; Glavas, Maria M; Ellis, Linda; Weinberg, Joanne

2005-06-09

Postnatal handling has been shown to attenuate some of the deficits in developmental outcome observed following prenatal ethanol exposure (E) although it appears to be ineffective at ameliorating the hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors that has been observed in adult E animals. However, the effects of postnatal handling on central regulation of HPA activity in E animals, particularly with regard to alterations in steady-state hypothalamic corticotropin-releasing factor (CRF) activity, have not been examined. In the present study, offspring from E, pair-fed (PF), and ad-libitum-fed control (C) groups were exposed to daily handling during the first 2 weeks of life (H) or were left entirely undisturbed until weaning (NH). Basal CRF and arginine vasopressin (AVP) mRNA in the parvocellular portion of the paraventricular nucleus (pPVN) of the hypothalamus were assessed at 90-110 days of age. Prenatal ethanol exposure resulted in elevated basal pPVN CRF mRNA levels compared to those in ad-libitum-fed controls. Handling altered CRF mRNA levels in a sex-specific and prenatal treatment-specific manner. Females showed no significant effects of handling. In contrast, handling decreased CRF mRNA levels in PF and C but not E males compared to their NH counterparts. There were no effects of prenatal ethanol or postnatal handling on AVP mRNA levels. These findings indicate that prenatal ethanol exposure results in elevated basal CRF mRNA levels in adulthood and that handling appears to be ineffective in normalizing those elevations, supporting the suggestion that altered basal HPA regulation in E animals may, at least in part, underlie their HPA hyperresponsiveness to stressors.

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

PubMed Central

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

2006-01-01

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

Vasopressin infusion into the lateral septum of adult male rats rescues progesterone-induced impairment in social recognition.

PubMed

Bychowski, M E; Mena, J D; Auger, C J

2013-08-29

It is well established that social recognition memory is mediated, in part, by arginine vasopressin (AVP). AVP cells within the bed nucleus of the stria terminalis (BST) and medial amygdala (MeA) send AVP-ergic projections to the lateral septum (LS). We have demonstrated that progesterone treatment decreases AVP immunoreactivity within the BST, the MeA and the LS, and that progesterone treatment impairs social recognition. These data suggested that progesterone may impair social recognition memory by decreasing AVP. In the present experiment, we hypothesized that infusions of AVP into the LS would rescue the progesterone-induced impairment in social recognition within adult male rats. One week after adult male rats underwent cannula surgery, they were given systemic injections of either a physiological dose of progesterone or oil control for 3 days. Four hours after the last injection, we tested social recognition memory using the social discrimination paradigm, a two-trial test that is based on the natural propensity for rats to be highly motivated to investigate novel conspecifics. Immediately after the first exposure to a juvenile, each animal received bilateral infusions of either AVP or artificial cerebrospinal fluid into the LS. Our results show that, as expected, control animals exhibited normal social discrimination. In corroboration with our previous results, animals given progesterone have impaired social discrimination. Interestingly, animals treated with progesterone and AVP exhibited normal social discrimination, suggesting that AVP treatment rescued the impairment in social recognition caused by progesterone. These data also further support a role for progesterone in modulating vasopressin-dependent behavior within the male brain. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II.

PubMed

Ortegon, H; Betts, D H; Lin, L; Coppola, G; Perrault, S D; Blondin, P; King, W A

2007-01-01

It appears that overt phenotypic abnormalities observed in some domestic animal clones are not transmitted to their progeny. The current study monitored Holstein heifers sired by a bull clone, Starbuck II, from weaning to puberty. Genomic stability was assessed by telomere length status and chromosomal analysis. Growth parameters, blood profiles, physical exams and reproductive parameters were assessed for 12 months (and compared to age-matched control heifers). Progeny sired by the clone bull did not differ (P>0.05) in weight, length and height compared to controls. However, progeny had lower heart rates (HR) (P=0.009), respiratory rates (RR) (P=0.007) and body temperature (P=0.03). Hematological profiles were within normal ranges and did not differ (P>0.05) between both groups. External and internal genitalia were normal and both groups reached puberty at expected ages. Progeny had two or three ovarian follicular waves per estrous cycle and serum progesterone concentrations were similar (P=0.99) to controls. Telomere lengths of sperm and blood cells from Starbuck II were not different (P>0.05) than those of non-cloned cattle; telomere lengths of progeny were not different (P>0.05) from age-matched controls. In addition, progeny had normal karyotypes in peripheral blood leukocytes compared to controls (89.1% versus 86.3% diploid, respectively). In summary, heifers sired by a bull clone had normal chromosomal stability, growth, physical, hematological and reproductive parameters, compared to normal heifers. Furthermore, they had moderate stress responses to routine handling and restraint.

Evaluation of guinea pig model for experimental Salmonella serovar Abortusequi infection in reference to infertility.

PubMed

Singh, B R; Alam, Javed; Hansda, D; Verma, J C; Singh, V P; Yadav, M P

2002-03-01

The present study conclusively revealed the role for Salmonella enterica subspecies enterica serovar Abortusequi in conception failure. None of the 12 guinea pigs conceived when orally exposed to sublethal dose of the pathogen during breeding, while 66.67% of animals in control group were found pregnant during same period of observation under similar conditions. Salmonella carrier animals also had drastic reduction in conception rate (16.67%). During mid pregnancy, S. Abortusequi exposure to guinea pigs through intravaginal, intramuscular and subcutaneous routes induced fetal death followed by resorption. While 2 out of 6 orally inoculated and 3 out of 6 intraperitonially inoculated guinea pigs aborted, in rest of the animals fetal death was followed by meceration and resorption. It was interesting to note that S. Abortusequi could not persist longer than a week in males while in pregnant females it could be detected for >10 weeks after inoculation. In late pregnancy, most of the exposed animals aborted and non aborting animals though had normal parturition, survival rate of their babies was nearly zero in comparison to the control group. The study revealed role for S. Abortusequi in impairing conception, abortion, early fetal deaths, fetal meceration and resorption. Further studies are required to identify factors responsible for increased susceptibility of females particularly during pregnancy.

Autonomic control of heart rate during orthostasis and the importance of orthostatic-tachycardia in the snake Python molurus.

PubMed

Armelin, Vinicius Araújo; da Silva Braga, Victor Hugo; Abe, Augusto Shinya; Rantin, Francisco Tadeu; Florindo, Luiz Henrique

2014-10-01

Orthostasis dramatically influences the hemodynamics of terrestrial vertebrates, especially large and elongated animals such as snakes. When these animals assume a vertical orientation, gravity tends to reduce venous return, cardiac filling, cardiac output and blood pressure to the anterior regions of the body. The hypotension triggers physiological responses, which generally include vasomotor adjustments and tachycardia to normalize blood pressure. While some studies have focused on understanding the regulation of these vasomotor adjustments in ectothermic vertebrates, little is known about regulation and the importance of heart rate in these animals during orthostasis. We acquired heart rate and carotid pulse pressure (P PC) in pythons in their horizontal position, and during 30 and 60° inclinations while the animals were either untreated (control) or upon muscarinic cholinoceptor blockade and a double autonomic blockade. Double autonomic blockade completely eradicated the orthostatic-tachycardia, and without this adjustment, the P PC reduction caused by the tilts became higher than that which was observed in untreated animals. On the other hand, post-inclinatory vasomotor adjustments appeared to be of negligible importance in counterbalancing the hemodynamic effects of gravity. Finally, calculations of cardiac autonomic tones at each position revealed that the orthostatic-tachycardia is almost completely elicited by a withdrawal of vagal drive.

Localization of tritiated vitamin A in lymph nodes of the mouse: an autoradiographic study of vitamin A-storing cells

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

Hirosawa, K.; Yamada, E.

1981-07-01

Localization of tritiated vitamin A in lymph nodes of the mouse was investigated by the use of light- and electron-microscopic autoradiography. Young male mice were fed a diet containing 3H-vitamin A acetate for a week. Lymph nodes were removed and prepared for autoradiography. Lipid droplets in fibroblast-like cells showed high concentrations of radioactivity. These cells were distributed around lymphatic sinuses and blood vessels. The cells can, therefore, be classified as ''vitamin A-storing cells'' according to criteria proposed earlier by Yamada and Hirosawa (1976). Control animals from the same litter were maintained on ordinary laboratory food for the same period andmore » examined by electron microscopy. Lipid-droplet-containing cells were found in the same areas as in the experimental animals but in fewer numbers. This suggests that the increased number of vitamin A-containing lipid droplets is due to hypervitaminosis A in the experimental animals. The presence of some cells containing these droplets in the control animals would imply that even under normal feeding conditions the animals ingested excess amounts of vitamin A, which was retained in lipid droplets. The stored vitamin A probably participates in metabolic processes such as the formation of glycoproteins in ground substance.« less

Effects of oxygen toxicity on cuprolinic blue-stained proteoglycans in alveolar basement membranes.

PubMed

Ferrara, T B; Fox, R B

1992-02-01

Effects of oxygen toxicity on distribution and density of proteoglycans in basement membranes of newborn rat lungs were assessed by electron microscopic analysis of tissues processed with cuprolinic blue, a cationic label that characteristically labels these anionically charged macromolecules. Newborn rats placed in greater than 95% oxygen at birth were killed at weekly intervals for 4 wk, and lung tissues fixed in 2.5% glutaraldehyde with 0.2% cuprolinic blue were processed for electron microscopy. Alveolar basement membranes from oxygen-treated and control animals were compared for differences in thickness and proteoglycan concentration and distribution. Results showed progressive thickening of alveolar basement membranes with increased duration of oxygen exposure. The normal distribution of proteoglycans, which is predominantly in the lamina rara externa of alveolar basement membranes, was frequently lost in thickened membranes found in oxygen-treated animals. Density of proteoglycans in these membranes decreased to 56% of normal by 2 wk of age and remained low with continued oxygen administration. Proteoglycan concentration in basement membranes on the interstitial side of alveolar capillaries in both control and oxygen-treated animals was low compared with proteoglycan concentration in basement membranes that opposed the alveolar air space, and administration of oxygen diminished these differences. These results demonstrate a direct alteration of proteoglycan distribution and density in the developing lung as a result of oxygen toxicity. This could result in decreased cell adhesion, influence the cellular response to lung injury, and contribute to the increased permeability seen with this disorder.

The APO*E3-Leiden mouse as an animal model for basal laminar deposit

PubMed Central

Kliffen, M.; Lutgens, E.; Daemen, M.; de Muinck, E. D; Mooy, C.; de Jong, P. T V M

2000-01-01

AIM—To investigate the APO*E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits.
METHODS—Eyes were obtained from APO*E3-Leiden transgenic mice on a high fat/cholesterol (HFC) diet (n=12) or on a normal mouse chow (n=6), for 9 months. As controls, eyes were collected from APO-E knockout mice on the same diets. From each mouse one eye was processed for microscopic evaluation and immunohistochemistry with a polyclonal antibody directed against human apo-E. Electron microscopy was also performed.
RESULTS—All 12 eyes of the APO*E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO*E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural aspects of this BLD were comparable with those seen in early BLD in humans, and BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was found in any of the control mice. Drusen were not detected in any of the mice.
CONCLUSION—These results indicate that APO*E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, this study supports the previously suggested involvement of dysfunctional apo-E in the accumulation of extracellular deposits in ARM.

 PMID:11090485

358 Histochemical Study of Allergic Inflammation in Conjunctiva From Ovalbumin Sensitized Rabbits after Ocular or Nasal Challenge

PubMed Central

Batle, Rocio; Vinuesa, Miguel; Bassan, Norberto; Martinez, Adriel; Giacomozzi, Florencia; Chaparro, Soledad; Torres, Valentin; Acebal, Florencia

2012-01-01

Background We previously demonstrated that subcutaneous sensitization with ovalbumin (OVA) induce generation of specific IgE antibodies and quantitative modifications in immune cells populations from different mucosal sites in rabbit. The aim of the study is characterization of eosinophil infiltration in conjunctival mucosa from OVA sensitized and ocular and nasal challenged rabbits. Methods Animals were divided into 4 groups: G1 (n = 9): normal control; G2 (n = 10): subcutaneous sensitized with OVA; G3 (n = 10): subcutaneous sensitized and conjunctival challenged with OVA; G4 (n = 9): subcutaneous sensitized and nasal challenged with OVA. Four hours after challenge animals were sacrificed and obtained samples were processed for histochemistry with cromotrope 2R for eosinophil detection. Cells were counted in 200 high power fields per group. Results Data were expressed as positive cells per high power field. Conjunctival mucosa: G1: 2.3; G2: 3.4; G3: 12.2; G4: 3.3 (G3 vs G1, G2 y G4 P < 0.001). Specific anti-OVA-IgE levels were evaluated by positive passive cutaneous anaphylaxis test (PCA) at 160 fold dilutions. Conclusions We observed an increase in the number of eosinophils-positive cells after local challenge in conjunctiva as compared to normal controls and sensitized and nasal challenged animals. We conclude that systemic sensitization with soluble antigen and conjunctival challenge induces modifications in number of eosinophil populations in conjunctiva but not in nasal challenged rabbits.

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

PubMed

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

2011-03-01

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

Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin

PubMed Central

Rowe, Peter S.N.; Matsumoto, Naoko; Jo, Oak D.; Shih, Remi N.J.; Oconnor, Jeannine; Roudier, Martine P.; Bain, Steve; Liu, Shiguang; Harrison, Jody; Yanagawa, Norimoto

2012-01-01

Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally, the growth plate and cortical bone of hyp femurs contained a massive accumulation of osteoblast-derived ASARM peptide(s) that was reduced in hyp animals treated with CA074 or pepstatin. This study confirms in vivo administration of cathepsin inhibitors improves bone mineralization in hyp mice. This may be due to a protease inhibitor mediated decrease in proteolytic degradation of the extracellular matrix and a reduced release of ASARM peptides (potent mineralization inhibitors). PMID:16762607

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-06-01

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

North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.

PubMed

Richardson, William H; Tanen, David A; Tong, Tri C; Betten, David P; Carstairs, Shaun D; Williams, Saralyn R; Cantrell, Frank L; Clark, Richard F

2006-02-01

North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non-native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba). A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD50. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log-rank testing to compare survival rates and times. Preliminary studies estimated the venom LD50 to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV-venom groups and normal saline-venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/- 37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study. When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical implications of this are unclear, given unchanged mortality rates.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon. PMID:21734804

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-06-01

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

A dual closed-loop control system for mechanical ventilation.

PubMed

Tehrani, Fleur; Rogers, Mark; Lo, Takkin; Malinowski, Thomas; Afuwape, Samuel; Lum, Michael; Grundl, Brett; Terry, Michael

2004-04-01

Closed-loop mechanical ventilation has the potential to provide more effective ventilatory support to patients with less complexity than conventional ventilation. The purpose of this study was to investigate the effectiveness of an automatic technique for mechanical ventilation. Two closed-loop control systems for mechanical ventilation are combined in this study. In one of the control systems several physiological data are used to automatically adjust the frequency and tidal volume of breaths of a patient. This method, which is patented under US Patent number 4986268, uses the criterion of minimal respiratory work rate to provide the patient with a natural pattern of breathing. The inputs to the system include data representing CO2 and O2 levels of the patient as well as respiratory compliance and airway resistance. The I:E ratio is adjusted on the basis of the respiratory time constant to allow for effective emptying of the lungs in expiration and to avoid intrinsic positive end expiratory pressure (PEEP). This system is combined with another closed-loop control system for automatic adjustment of the inspired fraction of oxygen of the patient. This controller uses the feedback of arterial oxygen saturation of the patient and combines a rapid stepwise control procedure with a proportional-integral-derivative (PID) control algorithm to automatically adjust the oxygen concentration in the patient's inspired gas. The dual closed-loop control system has been examined by using mechanical lung studies, computer simulations and animal experiments. In the mechanical lung studies, the ventilation controller adjusted the breathing frequency and tidal volume in a clinically appropriate manner in response to changes in respiratory mechanics. The results of computer simulations and animal studies under induced disturbances showed that blood gases were returned to the normal physiologic range in less than 25 s by the control system. In the animal experiments understeady-state conditions, the maximum standard deviations of arterial oxygen saturation and the end-tidal partial pressure of CO2 were +/- 1.76% and +/- 1.78 mmHg, respectively. The controller maintained the arterial blood gases within normal limits under steady-state conditions and the transient response of the system was robust under various disturbances. The results of the study have showed that the proposed dual closed-loop technique has effectively controlled mechanical ventilation under different test conditions.

Determination of the Threshold of Gravity for the Susceptibility to Kinetosis in Fish - a Centrifuge Experiment in the ZARM Drop-Tower employing gradually reduced Gravity

NASA Astrophysics Data System (ADS)

Anken, R.; Hilbig, R.

In the course of earlier experiments at diminished gravity conditions we have successfully used larval cichlid fish Oreochromis mossambicus as a vertebrate model system in investigating the basic cause of susceptibility to motion sickness kinetosis It was observed that most animals of a given batch reveal kinetoses i e performing looping responses LR or spinning movements SM at high quality microgravity 10-6g ZARM drop-tower whereas comparatively few individuals swim kinetotically at low quality microgravity LQM 0 03-0 05g during parabolic aircraft flights Anken and Hilbig Microgravity Sci Technol 15 52-57 2004 In order to gain further insights into a possible threshold of gravity for inducing motion sickness animals were subjected to drop-tower flights within a centrifuge The levels of gravity applied ranged from 0 009g until 0 3g The lowest level of gravity under which few normally swimming fish were observed ranged around 0 015g Since this is a very low level of gravity the normally swimming fish have to be considered to be either extremely sensitive to any force of gravity in order to use it as a cue for postural control or they use cues other than the residual gravity for maintaining equilibrium Most of the remaining kinetotically swimming animals showed LR whereas few exhibited SM With increasing gravity the ratio of normally swimming and spinning specimens increased accompanied by a decrease in the number of looping larvae Regarding the ratio a shift from LR to SM took place at around 0 02g At 0 3g all animals behaved

Effects of Ficus asperifolia on normal rat estrus cyclicity

PubMed Central

Ngadjui, Esther; Watcho, Pierre; Nguelefack, Telesphore Benoit; Kamanyi, Albert

2013-01-01

Objective To evaluate Ficus asperifolia (Moraceae) (F. asperifolia) effecting on regular estrus cycle of Wistar rats. Methods Air-dried fruits of F. asperifolia were extracted using water. Prior to the test, vaginal smear was monitored daily for a 3-week period to select females with normal (regular) estrous cycle. Those with regular estrus cycle weighing between 150–170 g were randomized into three sets of 15 animals each. Each set was then divided into three groups: Group 1 (control) was orally administered with distilled water (10 mL/kg body weight) once a day for 1 week starting from the proestrus stage. Groups 2 and 3 were respectively treated with 100 and 500 mg/kg body weight of the plant aqueous extract. The two other sets of 15 animals each were similarly treated as the first set for 3 weeks and 6 weeks respectively. Estrus cycle pattern was monitored before and during plant extract application whereas lipid profile, ovary, uterus and liver growth indices were determined at the end of each treatment. Results F. asperifolia did not disrupt (0%) the order of appearance of normal estrus cycle stages, namely, proestrus, estrus, metestrus and diestrus. Short-term treatment (1 week duration) exhibited high frequency of appearance of proestrus and estrus stages while mid- (3 weeks) and long-term (6 weeks) treatments revealed constancy in the frequency of all stages irrespective to animal groups. The plasma and organ lipid profile, as well as ovary, uterus and liver growth remained unchanged when compared to distilled water-treated animals. Following long-term administration of plant extract (6 weeks), no adverse effect was noticed. Conclusions Our data partially support the use of F. asperifolia in common medicine. PMID:23570017

Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol

PubMed Central

Manzoor, N.F.; Chen, G.; Kaltenbach, J.A.

2013-01-01

Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4 h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 µM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system. PMID:23721928

Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol.

PubMed

Manzoor, N F; Chen, G; Kaltenbach, J A

2013-07-26

Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 μM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was usually not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system. Copyright © 2013 Elsevier B.V. All rights reserved.

The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.

PubMed

Good, M; Clegg, T A; Costello, E; More, S J

2011-11-01

In national bovine tuberculosis (BTB) control programmes, testing is generally conducted using a single source of bovine purified protein derivative (PPD) tuberculin. Alternative tuberculin sources should be identified as part of a broad risk management strategy as problems of supply or quality cannot be discounted. This study was conducted to compare the impact of different potencies of a single bovine PPD tuberculin on the field performance of the single intradermal comparative tuberculin test (SICTT) and single intradermal test (SIT). Three trial potencies of bovine PPD tuberculin, as assayed in naturally infected bovines, namely, low (1192IU/dose), normal (6184IU/dose) and high (12,554IU/dose) were used. Three SICTTs (using) were conducted on 2102 animals. Test results were compared based on reactor-status and changes in skin-thickness at the bovine tuberculin injection site. There was a significant difference in the number of reactors detected using the high and low potency tuberculins. In the SICTT, high and low potency tuberculin detected 40% more and 50% fewer reactors, respectively, than normal potency tuberculin. Furthermore, use of the low potency tuberculin in the SICTT failed to detect 20% of 35 animals with visible lesions, and in the SIT 11% of the visible lesion animals would have been classified as negative. Tuberculin potency is critical to the performance of both the SICTT and SIT. Tuberculin of different potencies will affect reactor disclosure rates, confounding between-year or between-country comparisons. Independent checks of tuberculin potency are an important aspect of quality control in national BTB control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Effect of biopesticide Pythium oligandrum broth on gummy stem blight in cucumber seedlings, animal health and plant growth].

PubMed

Geng, Mingming; Jia, Ruilian; Sui, Zongming; Huang, Jianguo

2016-07-04

Biopesticides are safe and environment friendly. We evaluated the biocontrol effect of Pythium oligandrum broth (POB) and its toxicity to animals and plant growth. Animal, antagonist, pot, and field experiments with mice, Mycosphaerella melonis, and cucumber seedlings were carried out to study animal toxicity, control of gummy stem blight, plant growth, fruit yield and quality with POB produced from self-isolated P. oligandrum CQ2010. Mouse showed normal weight, appearances, performances and no pathogenic changes in organs and tissues with a large amount of POB supplied by lavage. The inhibition rate of POB against M. melonis was 51.95%, similar to thiophanate methy (800 times dilution) but much higher than chlorothalonil (200 times dilution). Malondialdehyde concentration was reduced whereas activities of peroxidase and superoxide dismutase were stimulated in seedling leaves irrespective of POB supplied before and after pathogenic inoculation. POB also decreased the pathogenic incidence and disease index with relative control efficacy from 54.8% to 64.1%. Thus, POB could alleviate cell membrane damage caused by pathogenic microbes, stimulate physiological reactions related to disease defense, and increase disease-resistant abilities of plants. Moreover, POB increased chlorophyll content, root activity, and uptake of nitrogen, phosphorus and potassium, resulting in growth acceleration, fruit yield increment, and quality improvement. POB is safe to animals and could control gummy stem blight of cucumber seedlings, promote plant growth, increase fruit yield, and improve the qualities.

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

PubMed Central

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

1979-01-01

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

Differential responsiveness in VEGF receptor subtypes to hypoxic stress in various tissues of plateau animals.

PubMed

Xie, Hui-Chun; Li, Jin-Gang; He, Jian-Ping

2017-05-04

With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress. ELISA and Western blot analysis were employed to determine HIF-1alpha and the protein expression of VEGFRs in control animals and plateau pikas. We further blocked HIF-1alpha signal to determine if HIF-1alpha regulates alternations in VEGFRs in those tissues. We hypothesized that responsiveness of VEGFRs in the major end organs of plateau animals is differential with insult of hypoxic stress and is modulated by low oxygen sensitive HIF-1alpha. Our results show that hypoxic stress induced by exposure of lower O(2) for 6 h significantly increased the levels of VEGFR-2 in skeletal muscle, heart and lung and the increases were amplified in plateau pikas. Our results also demonstrate that hypoxic stress enhanced VEGFR-3 in lungs of plateau animals. Nonetheless, no significant alternations in VEGFR-1 were observed in those tissues with hypoxic stress. Moreover, we observed decreases of VEGFR-2 in skeletal muscle, heart and lung; and decreases of VEGFR-3 in lung following HIF-1alpha inhibition. Overall, our findings suggest that in plateau animals 1) responsiveness of VEGFRs is different under hypoxic environment; 2) amplified VEGFR-2 response appears in skeletal muscle, heart and lung, and enhanced VEGFR-3 response is mainly observed in lung; 3) HIF-1alpha plays a regulatory role in the levels of VEGFRs. Our results provide the underlying cellular and molecular mechanisms responsible for hypoxic environment in plateau animals, having an impact on research of physiological and ecological adaptive responses to acute or chronic hypoxic stress in humans who living at high attitude and who live at a normal sea level but suffer from hypoxic disorders.

A potential vaccine for cocaine abuse prophylaxis.

PubMed

Bagasra, O; Forman, L J; Howeedy, A; Whittle, P

1992-01-01

Presently, there are estimated to be 1.5 to 2.0 million individuals infected with HIV-1 in the U.S. and about 12 million worldwide. In the U.S. over 90% of reported cases of AIDS occurred among two subgroups, homosexual males and intravenous substance abusers (IVSAs). Currently, there is no anti-cocaine addiction medication available. In order to explore vaccination as an alternative means for protection against cocaine addition, we immunized inbred male Fisher rats with either cocaine emulsification in complete Freund adjuvant (CFA) or with cocaine conjugated with keyhole limpet hemocyanin (KLH), as carrier plus CFA. Animals were initially immunized with 0.1 mg/animal of cocaine or cocaine-KLH. Animals were given a booster with the corresponding agents after 4 weeks. Ten animals/group were used. Controls received normal saline at the time of immunizations. These animals were injected, intraperitoneally, with 25 mg/kg of cocaine, and were examined for the analgesic effect of cocaine by the hot plate method. The average analgesic effect of cocaine was significantly reduced (p greater than 0.03) in animals immunized with cocaine-KLH (13.77 s) as compared to saline controls (21.6 s). Fifty percent of the animals (5/10) in the cocaine-KLH group and 33% of the animals (3/9) in the cocaine immunized group appeared completely resistant to the effect of cocaine on the central nervous system (CNS). We also have determined the levels of cocaine-specific antibodies produced by each animal by an ELISA method. Degree of protection from cocaine seems to correlate well with the amount of anti-cocaine antibodies produced by each animal (-0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

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

Application of Model Animals in the Study of Drug Toxicology

NASA Astrophysics Data System (ADS)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

PubMed

Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

2015-09-01

Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

Early-effect of bariatric surgery (Scopinaro method) on intestinal hormones and adipokines in insulin resistant Wistar rat.

PubMed

Dib, N; Kiciak, A; Pietrzak, P; Ferenc, K; Jaworski, P; Kapica, M; Tarnowski, W; Zabielski, R

2013-10-01

Bariatric surgery consists in duodenal exclusion from the food passage in obese patients with coexistent type 2 diabetes. Nowadays bariatric surgery is considered the most effective method of glycemic index normalization and insulin resistance reduction. Recent results on obese and non-obese rats showed remission of type 2 diabetes symptoms within few days after the surgery. The aim of the present work was to analyze the mechanisms of neuro-hormonal regulation responsible for early normalization of metabolic syndrome after bariatric surgery. In present study the concentration of selected intestinal hormones and adipokines in blood plasma and gastrointestinal tissues were analyzed. Study was conducted on Wistar rats. Animals were divided into three groups (each n=6): control (SH) shame-operated rats; animals in which visceral fat tissue was extracted (LP); and rats in which Scopinaro bariatric surgery was performed (BPD). Immunochemistry analysis of blood plasma showed decrease of insulin concentration in BPD and LP and increase of polypeptide YY (PYY) in BPD group as compared to the control. In duodenal mucosa homogenates the tendency to reduce insulin in LP and BPD group, and increase PYY and visfatin in BPD group was observed. Histometry analysis showed reduction of mucosa thickness in excluded segments of gastrointestinal tract in BPD group as compared to the SH and LP. Concluding, model studies on rats allowed better understanding of mechanisms important for early normalization of glycemic index and insulin resistance reduction in rats.

Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats

PubMed Central

2011-01-01

Background Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS) production. Whey protein (WP) is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN), a wounded diabetic group (WD) and a wounded diabetic group orally supplemented with whey protein (WDWP) at a dose of 100 mg/kg body weight. Results Whey protein was found to significantly decrease the levels of malondialdehyde (MDA), nitric oxide (NO) and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1β, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. Conclusion In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines. PMID:22168406

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

PubMed

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

2016-01-01

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

Toxicity evaluation of hydrophilic CdTe quantum dots and CdTe@SiO2 nanoparticles in mice.

PubMed

Sadaf, Asma; Zeshan, Basit; Wang, Zhuyuan; Zhang, Ruohu; Xu, Shuhong; Wang, Chunlei; Cui, Yiping

2012-11-01

Quantum dots have drawn tremendous attention in the field of in vitro and small animal in vivo fluorescence imaging in the last decade. However, concerns over the cytotoxicity of their heavy metal constituents have limited their use in clinical applications. Here, we report our comparative studies on the toxicities of quantum dots (QDs) and silica coated CdTe nanoparticles (NPs) to mice after intravenous injection. The blood cells analysis showed significant increased level of white blood cells (WBCs) in groups treated with CdTe QDs as compared to the control while red blood cells (RBCs) and platelet counts were normal in treated as well as control groups. The concentration of biochemical markers of hepatic damage, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were in the normal range in all the groups. However, renal function analyses of mice showed significantly increased in the concentration of blood urea nitrogen (BUN) and creatinine (CREA) in mice treated with CdTe QDs while remained within normal ranges in both the CdTe@SiO2 NPs and control group. The results of histopathology showed that the CdTe QDs caused mild nephrotoxicity while other organs were normal and no abnormalities were detected in control and CdTe@SiO2 treated group. These findings suggest that the nephrotoxicity could be minimized by silica coating which would be useful for many biomedical applications.

Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

PubMed

Wemyss-Holden, S A; Robertson, G S; Dennison, A R; de la M Hall, P; Fothergill, J C; Jones, B; Maddern, G J

2000-09-01

An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors. Copyright 2000 Academic Press.

Biochemical correlates in an animal model of depression

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

Johnson, J.O.

1986-01-01

A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus.more » Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action.« less

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique

NASA Astrophysics Data System (ADS)

Bellotti, Mariela I.; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J.

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique.

PubMed

Bellotti, Mariela I; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

The efficacy of the appetite suppressant, diethylpropion, is dependent on both when it is given (day vs. night) and under conditions of high fat dietary restriction.

PubMed

Kalyanasundar, B; Solorio, Jessica; Perez, Claudia I; Hoyo-Vadillo, Carlos; Simon, Sidney A; Gutierrez, Ranier

2016-05-01

Obesity is a public health problem caused by excessive consumption of high caloric diets and/or lack of physical activity. Although treatments for obesity include low caloric diets and exercise programs, these activities frequently are supplemented with appetite suppressants. For the short-term treatment of weight loss, diethylpropion (DEP) is a commonly used appetite suppressant. However, little is known with regard to how to improve its weight loss efficacy. We therefore evaluated, in rats, two administration protocols where the animals received daily injections of DEP. First, when these nocturnal animals were normally active (at night) and when they were normally inactive (daytime), and second, with or without high fat dietary restriction (HFDR). We observed that DEP induced a greater weight-loss administered when the animals were in their active phase than in their inactive phase. Moreover, DEP's administration during the inactive phase (and to a lesser degree in the active phase) promotes the consumption of food during normal sleeping time. In addition, we found that DEP-induced weight loss under ad libitum access to a HF diet, but its efficacy significantly improved under conditions of HFDR. In summary, the efficacy of DEP, and presumably other like appetite suppressants, is enhanced by carefully controlling the time it is administered and under dietary restriction of HF diets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Olivocochlear Efferent Control in Sound Localization and Experience-Dependent Learning

PubMed Central

Irving, Samuel; Moore, David R.; Liberman, M. Charles; Sumner, Christian J.

2012-01-01

Efferent auditory pathways have been implicated in sound localization and its plasticity. We examined the role of the olivocochlear system (OC) in horizontal sound localization by the ferret and in localization learning following unilateral earplugging. Under anesthesia, adult ferrets underwent olivocochlear bundle section at the floor of the fourth ventricle, either at the midline or laterally (left). Lesioned and control animals were trained to localize 1 s and 40ms amplitude-roved broadband noise stimuli from one of 12 loudspeakers. Neither type of lesion affected normal localization accuracy. All ferrets then received a left earplug and were tested and trained over 10 d. The plug profoundly disrupted localization. Ferrets in the control and lateral lesion groups improved significantly during subsequent training on the 1 s stimulus. No improvement (learning) occurred in the midline lesion group. Markedly poorer performance and failure to learn was observed with the 40 ms stimulus in all groups. Plug removal resulted in a rapid resumption of normal localization in all animals. Insertion of a subsequent plug in the right ear produced similar results to left earplugging. Learning in the lateral lesion group was independent of the side of the lesion relative to the earplug. Lesions in all reported cases were verified histologically. The results suggest the OC system is not needed for accurate localization, but that it is involved in relearning localization during unilateral conductive hearing loss. PMID:21325517

Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes.

PubMed

Wilson, Rachel D; Islam, Md Shahidul

2012-01-01

The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60 g) were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Fructose-10 (FR10), Fructose-20 (FR20), Fructose-30 (FR30) and Fructose-40 (FR40) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum, respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40 mg/kg b.w.) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose levels > 300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20, FR30 and FR40 groups were eliminated from the study due to the severity of diabetes and the FR10 group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-β) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BWSTZ injected rat can be a new and alternative model for T2D.

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats

PubMed Central

Al-Dbass, Abeer M.; Al- Daihan, Sooad K.; Bhat, Ramesa Shafi

2012-01-01

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury. PMID:23961190

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats.

PubMed

Al-Dbass, Abeer M; Al-Daihan, Sooad K; Bhat, Ramesa Shafi

2012-07-01

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.

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

PubMed Central

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

2015-01-01

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

Effects of dietary glutamine on inflammatory mediator gene expressions in rats with streptozotocin-induced diabetes.

PubMed

Tsai, Pei-Hsuan; Yeh, Chui-Li; Liu, Jun-Jen; Chiu, Wan-Chun; Yeh, Sung-Ling

2012-03-01

This study investigated the effects of glutamine (Gln) supplementation on gene expressions of inflammatory mediators and cytokines associated with T-helper cell type 17 (Th17) regulation in diabetic rats. There were one normal control group and two diabetic groups in this study. Rats in the normal control group were fed a regular chow diet. One diabetic group (DM) was fed a common semipurified diet, and the other diabetic group received a diet in which part of the casein was replaced by Gln (DM-Gln), which provided 25% of the total amino acid nitrogen for 8 wk. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin. Rats with blood glucose levels exceeding 200 mg/dL were considered diabetic. Blood samples and blood mononuclear cells of the animals were collected at the end of the study for further analysis. Gene expressions of transforming growth factor-β1 and interleukin-17A did not differ in blood mononuclear cells among the three groups. Expressions of interleukin-6, interleukin-23, monocyte chemotactic protein-1, and the receptor of the advanced glycated endproducts gene were higher in blood mononuclear cells and the ratio of reduced to oxidized glutathione was lower in erythrocytes in the DM group than in the normal control group. Messenger RNA expressions of these genes were lower, whereas the ratio of reduced to oxidized glutathione was higher in the DM-Gln group than in the DM group. Supplemental dietary Gln increased the antioxidant potential and downregulated the expressions of inflammatory mediators. However, Th17 might not be an important involved pathway and the regulatory effect of Gln on Th17 immune response was not obvious in this animal model. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2014-04-01

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

[Taurine as a regulator of fluid-electrolyte balance and arterial pressure].

PubMed

Ciechanowska, B

1997-01-01

Taurine is a sulfonic beta-amino acid which occurs in the highest concentration in the brain, the retina and in the myocardium. In cardiomyocytes it presents about 50% of free amino acids and plays a role as an osmoregulator, an inotropic factor and has an antiarrhythmic property. Moreover, taurine lowers arterial pressure by extension of diuresis and by vasodilatation. Similar effect on the vascular system and arterial pressure is exerted by atrial natriuretic peptide (ANP). Increase of both ANP secretion and myocardial taurine concentration is present in the same diseases as congestive cardiac failure, hypertension and hypernatremia. The aim of the study was the evaluation of general taurine depletion, caused by making the rats drink guanidinoethyl sulfonate (GES)--an inhibitor of taurine transport affecting fluid balance and arterial pressure as well as plasma ANP concentration under normal conditions and after increase of sodium load. The 103 male Wistar rats weighing 250-300 g were used. The animals were separated into 5 groups. Control group received tap water to drink. Group II was sodium-loaded by drinking 171 mmol/l NaCl. In group III depletion of taurine was obtained by the intake of 60 mmol/l GES. Rats in group IV were drinking 60 mmol/l GES in 171 mmol/l NaCl. Group V was made to drink 200 mmol/l taurine in 171 mmol/l NaCl. All animals had standard food and were able at any time to drink. Duration of the experiment was 20 days. At the onset and after 10 and 20 days the rats were weighed and their systolic blood pressure was measured by tail plethysmography. After 10 and 20 days of the study, plasma and myocardium taurine concentration, ANP, hematocrit, plasma osmolity, natremia, kalemia, urea and creatinine concentrations were determined. Taking GES for 20 days led to 43% decrease of plasma taurine and its myocardium content about 50% as compared to control group (Tab. 2). High, statistically significant correlation (r = 0.50, p < 0.001) between myocardium taurine and plasma ANP was found. The animals with taurine depletion had significantly lower (about 30%) plasma ANP concentration (Tab. 3), higher natremia (Tab. 4) and their arterial pressure increased due to sodium load. Systolic pressure was 11 mm Hg higher in that group in comparison to control and other groups (Tab. 1). However, the sodium-loading of the rats that drank taurine solution led to an increase of hematocrit, plasma osmolity, urea concentration and body mass gain as compared to control group, but without any arterial pressure increase. The sodium-loaded rats with normal plasma and myocardium taurine concentration were affected in a similar manner. The rats with higher myocardium taurine concentration had lower heart mass index. Results of this work lead to the following conclusions: 1. Depletion of taurine in hearts of examined rats leads to a decrease of plasma atrial natriuretic peptide (ANP) concentration in plasma. 2. ANP secretion caused by salt loading is lower in animals with taurine depletion than in normal animals. 3. Sodium-loading of animals with taurine depletion leads to hypernatremia and to an increase of arterial pressure. 4. Addition of taurine to animals loaded with sodium may lead to their dehydration.

Morphological and biochemical examination of Cosmos 1887 rat heart tissue. Part 1: Ultrastructure

NASA Technical Reports Server (NTRS)

Philpott, D. E.; Popova, I. A.; Kato, K.; Stevenson, J.; Miquel, J.; Sapp, W.

1990-01-01

Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel. Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space.

Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

PubMed

Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

2015-09-01

Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. © 2015 John Wiley & Sons Ltd.

Evaluation of novel urinary renal biomarkers with a cisplatin model of kidney injury: effects of collection period.

PubMed

Pinches, Mark D; Betts, Catherine J; Bickerton, Susan J; Beattie, Laura; Burdett, Lisa D; Thomas, Helen T; Derbyshire, Nicola A; Moores, Michele

2012-04-01

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. To date, all evaluation studies have been made using 18 to 24 hour collection periods. However, shorter, more welfare friendly, urine collection periods are also used in industry. In this article, we quantify urinary biomarker concentration in serial paired sequential short and long urine collections from male rats administered varying concentrations of cisplatin. We calculate the rate of biomarker excretion in normal animals for both collection periods and the bias and correlation in urinary biomarker concentration between collection periods in dosed and control animals, and we estimate the level of agreement in biomarker concentration between both collection periods. We conclude that although there are minor differences in the concentration of some urinary biomarkers that are dependent upon the time and duration of collection, shorter collection protocols do not influence subsequent interpretation of normalized urinary biomarker data for most biomarkers.

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

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

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

1988-02-01

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

Role of tissue engineered collagen based tridimensional implant on the healing response of the experimentally induced large Achilles tendon defect model in rabbits: a long term study with high clinical relevance

PubMed Central

2013-01-01

Background Tendon injury is one of the orthopedic conditions poses with a significant clinical challenge to both the surgeons and patients. The major limitations to manage these injuries are poor healing response and development of peritendinous adhesions in the injured area. This study investigated the effectiveness of a novel collagen implant on tendon healing in rabbits. Results Seventy five mature White New-Zealand rabbits were divided into treated (n = 55) and control (n = 20) groups. The left Achilles tendon was completely transected and 2 cm excised. The defects of the treated animals were filled with collagen implants and repaired with sutures, but in control rabbits the defects were sutured similarly but the gap was left untreated. Changes in the injured and normal contralateral tendons were assessed weekly by measuring the diameter, temperature and bioelectrical characteristics of the injured area. Clinical examination was done and scored. Among the treated animals, small pilot groups were euthanized at 5, 10, 15, 20, 30, 40 and 60 (n = 5 at each time interval) and the remainder (n = 20) and the control animals at 120 days post injury (DPI). The lesions of all animals were examined at macroscopic and microscopic levels and the dry matter content, water delivery and water uptake characteristics of the lesions and normal contralateral tendons of both groups were analyzed at 120 DPI. No sign of rejection was seen in the treated lesions. The collagen implant was invaded by the inflammatory cells at the inflammatory phase, followed by fibroplasia phase in which remnant of the collagen implant were still present while no inflammatory reaction could be seen in the lesions. However, the collagen implant was completely absorbed in the remodeling phase and the newly regenerated tendinous tissue filled the gap. Compared to the controls, the treated lesions showed improved tissue alignment and less peritendinous adhesion, muscle atrophy and fibrosis. They also showed significantly better clinical scoring, indices for water uptake and water absorption, and bioelectrical characteristics than the controls. Conclusion This novel collagen implant was biodegradable, biocompatible and possibly could be considered as a substitute for auto and allografts in clinical practice in near future. PMID:23672303

Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

PubMed

Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

2015-02-01

The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Right dorsal colon ultrasonography in normal adult ponies and miniature horses.

PubMed

Siwinska, Natalia; Zak, Agnieszka; Baron, Monika; Cylna, Marta; Borowicz, Hieronim

2017-01-01

The aim of this study was to determine the normal location, wall thickness and motility of the right dorsal colon in adult ponies and miniature horses. The abdominal ultrasonography examination was performed in a study group consisting of 23 ponies and miniature horses and in a control group comprising ten Thoroughbred horses. The procedure was performed in unsedated standing animals. The location and the thickness of the right dorsal colonic wall was examined on the right side of the abdomen between the 10th and the 14th intercostal space. The contractility was recorded in the 12th intercostal space. A comparative analysis between the study group and control group was carried out using the Student's t-test. Pearson's linear correlation coefficient was used to calculate the correlation between the thickness of the colonic wall as well as the number of peristaltic movements and age, wither height and body mass of the animals. The right dorsal colon was identified in all the horses in the 12th intercostal space. In all the intercostal spaces the mean ± standard deviation (SD) wall thickness of the right dorsal colon was 0.27 ± 0.03 cm in the horses from the study group and 0.37 ± 0.03 cm in the control horses. The mean number of peristaltic contractions was 4.05 ± 1.07 per minute in the animals from the study group and 1.7 ± 0.46 contractions per minute in the control group. The values of the ultrasonographic wall thickness and peristaltic motility in small breed horses in the present study were different from the values obtained for large breed horses. The study also found that the right dorsal colon in small breed horses is physiologically located in the 12th intercostal space. This suggests that different reference values should be used in small horse breeds when performing an ultrasound examination.

Right dorsal colon ultrasonography in normal adult ponies and miniature horses

PubMed Central

Zak, Agnieszka; Baron, Monika; Cylna, Marta; Borowicz, Hieronim

2017-01-01

The aim of this study was to determine the normal location, wall thickness and motility of the right dorsal colon in adult ponies and miniature horses. The abdominal ultrasonography examination was performed in a study group consisting of 23 ponies and miniature horses and in a control group comprising ten Thoroughbred horses. The procedure was performed in unsedated standing animals. The location and the thickness of the right dorsal colonic wall was examined on the right side of the abdomen between the 10th and the 14th intercostal space. The contractility was recorded in the 12th intercostal space. A comparative analysis between the study group and control group was carried out using the Student’s t-test. Pearson’s linear correlation coefficient was used to calculate the correlation between the thickness of the colonic wall as well as the number of peristaltic movements and age, wither height and body mass of the animals. The right dorsal colon was identified in all the horses in the 12th intercostal space. In all the intercostal spaces the mean ± standard deviation (SD) wall thickness of the right dorsal colon was 0.27 ± 0.03 cm in the horses from the study group and 0.37 ± 0.03 cm in the control horses. The mean number of peristaltic contractions was 4.05 ± 1.07 per minute in the animals from the study group and 1.7 ± 0.46 contractions per minute in the control group. The values of the ultrasonographic wall thickness and peristaltic motility in small breed horses in the present study were different from the values obtained for large breed horses. The study also found that the right dorsal colon in small breed horses is physiologically located in the 12th intercostal space. This suggests that different reference values should be used in small horse breeds when performing an ultrasound examination. PMID:29065146

Influence of boron supplementation on performance, immunity and antioxidant status of lambs fed diets with or without adequate level of calcium

PubMed Central

Mondal, S.; Pattanaik, A. K.; Verma, A. K.

2017-01-01

Little is known about biological significance of effects of dietary Boron (B) and Calcium (Ca) interaction on health and production of farm animals. This is a preliminary investigation to evaluate the effects of B supplementation in lambs fed diets with (normal) or without adequate (low) levels of Ca. Twenty-four crossbred ram lambs were randomly distributed into four groups with six animals each in a 2x2 factorial design namely, normal-Ca diet (NCa) and low-Ca diet (LCa) fed without or with 40 ppm B (NCaB-40 and LCaB-40). The lambs were fed paddy straw and hybrid napier hay-based total mixed ration (60 roughage: 40 concentrate) during 180 days experimental period. Compared to control, the LCa diet lowered (P<0.01) average daily gain of lambs, but B-supplementation (LCaB-40) of the same nullified the effect. The lowered (P<0.05) total antioxidant activity and humoral immune response in lambs fed LCa diet were restored (P>0.05) to become at par with the control (NCa) upon supplementation of B (LCaB-40). The mRNA expression of SOD1 was lowered (P<0.05) due to LCa diet feeding which too was normalized on B-supplementation to become at par (P>0.05) with the control (NCa). Further, B-supplementation restored lowered (P<0.05) SOD1 gene expression on LCa diet, but enhanced (P<0.05) that in NCaB-40 group, when compared to the control (NCa) diet fed animals. However, these variations were not reflected in the SOD activity in the erythrocytes. The cell-mediated immune response was higher (P<0.05) in lambs fed LCa and LCaB-40 groups and there was no significant interaction between the levels of either Ca or B in diets with the period of immune response measurement. B- supplementation of LCa diet ameliorated tissue degenerative changes in liver and kidney. It was concluded that feeding LCa diet to lambs resulted in reduced growth rate, total antioxidant activity, humoral immune response along with degenerative changes in liver and kidney tissues, but B-supplementation of such diet restored most of these changes and ameliorated histopathological alterations. PMID:29141035

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

PubMed

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

1996-06-01

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

[Evaluation of grip strength in normal and obese Wistar rats submitted to swimming with overload after median nerve compression].

PubMed

Coradinia, Josinéia Gresele; Kakihata, Camila Mayumi Martin; Kunz, Regina Inês; Errero, Tatiane Kamada; Bonfleur, Maria Lúcia; Bertolini, Gladson Ricardo Flor

2015-01-01

To verify the functionality through muscle grip strength in animals with obesity induced by monosodium glutamate (MSG) and in control animals, which suffered compression of the right median nerve, and treated with swimming with overload. During the first five days of life, neonatal Wistar rats received subcutaneous injections of MSG. The control group received a hypertonic saline solution. Forty-eight rats were divided into six groups: G1 (control); G2 (control + injury); G3 (control + injury + swimming); G4 (obese); G5 (obese + injury); G6 (obese + injury + swimming). The animals in groups G2, G3, G5 and G6 were submitted to compression of the median nerve and G3 and G6 groups were treated, after injury, with swimming exercise with load for three weeks. The swimming exercise had a progressive duration, according to the week, of 20, 30 and 40minutes. Muscle strength was assessed using a grip strength meter preoperatively and on the 3rd, 7th, 14th and 21st days after surgery. The results were expressed and analyzed using descriptive and inferential statistics. When the grip strength was compared among assessments regardless of group, in the second assessment the animals exhibited lower grip strength. G1 and G4 groups had greater grip strength, compared to G2, G3, G4 and G6. The swimming exercise with overload has not been effective in promoting improvement in muscle grip strength after compression injury of the right median nerve in control and in obese-MSG rats. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Morphometrical investigations on the reproductive activity of the ovaries in rats subjected to immobilization and to motion activity

NASA Technical Reports Server (NTRS)

Konstantinov, N.; Cheresharov, L.; Toshkova, S.

1982-01-01

Wistar-strain white female rats were divided into three groups, with the first group subjected to motion loading, the second used as control, and the third group was immobilized. A considerable reduction in numbers of corpora lutea was observed in the immobilized group, together with smaller numbers of embryos, high percent of embryo mortality, fetal growth retardation, and endometrium disorders. The control group showed no deviation from normal conditions, and there was slight improvement in reproductive activity of animals under motion loading.

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

PubMed

Boudène, C; Collas, E; Jenkins, C

1975-01-01

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

Evaluation of anti-obesity activity of duloxetine in comparison with sibutramine along with its anti-depressant activity: an experimental study in obese rats.

PubMed

Chudasama, H P; Bhatt, P A

2009-11-01

5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.

Efficacy and safety of damage control in experimental animal models of injury: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Although abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury. Methods/design We will search electronic databases (Medline, Embase, PubMed, Web of Science, Scopus, and the Cochrane Library), conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery (or specific definitive surgical interventions). Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim and fill method to estimate the potential influence of this bias on pooled summary estimates. Discussion This study will evaluate the efficacy and safety of damage control in experimental animal models of injury. Study results will be used to guide future clinical evaluations of damage control surgery, determine which animal study outcomes may potentially be generalizable to the clinical setting, and to provide guidelines to strengthen the conduct and relevance of future pre-clinical studies. PMID:25416175

EPHRIN-A5 REGULATES INTER-MALE AGGRESSION IN MICE

PubMed Central

Sheleg, Michal; Yochum, Carrie L.; Richardson, Jason R.; Wagner, George C.; Zhou, Renping

2015-01-01

The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice. PMID:25746458

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2014-05-01

in control versus pilocarpine-treated (suffering status epilepticus ) group of animals that were injected with saline instead of levetiracetam for 1...month (Figure 1A). As previously reported we detected a significant 4.4% increase in normalized peak fluorescence in status epilepticus (SE) group...slices) (Figure A, b3). These data is consistent with our previous findings that status epilepticus induce an abnortmal increase in presynaptic

Effects provoked by chronic undernourishment on the fibre type composition and contractility of fast muscles in male and female developing rats.

PubMed

Pereyra-Venegas, J; Segura-Alegría, B; Guadarrama-Olmos, J C; Mariscal-Tovar, S; Quiróz-González, S; Jiménez-Estrada, I

2015-10-01

In this study, we compare the effects of pre- and post-natal food deprivation on the relative proportion of fibre types and contractile responses in the extensor digitorum longus (EDL) muscle of female and male rats at different post-natal ages. EDL muscles from undernourished male (UM) rats showed a higher proportion of Type IIB than IIA fibres and larger normalized twitch responses (with respect to muscle weight) than those of controls (CM). In contrast, EDL muscles from control (CF) and undernourished female rats (UF) showed no significant differences in their fibre type composition and normalized twitch forces at most of the ages analysed. Our data are indicative that the EDL muscles from undernourished males are more susceptible to the effects exerted by low food income than the EDL muscles from female rats. It is proposed that changes in the reactive oxygen species (ROS) concentration and hormonal factors, due to undernutrition, are involved in the alterations observed in the fibre type composition and force production of EDL muscles in undernourished male rats and that estrogens may have an antioxidant protective role on the undernourished EDL muscles in female rats. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Effect of Nigella sativa (black seeds) against methotrexate-induced nephrotoxicity in mice.

PubMed

Ahmed, Jawad Hassan; Abdulmajeed, Isra Mohammed

2017-01-01

To evaluate the protective effect of Nigella sativa (NS) against nephrotoxicity of methotrexate (MTX) in mice. Four groups of Swiss albino male mice, eight in each group were used. The study was carried on between October 2014 and April 2015. Group 1 (control) were administered 0.3 ml distilled water orally daily for 21 days and injected with normal saline (0.25 ml) IP weekly. Group 2 (MTX group) were treated with MTX, 10 mg/kg IP weekly, while Group 3 were treated with 0.125 ml of NS oil by mouth daily and injected with normal saline (0.25 ml) IP weekly. Group 4 received 0.125 ml of NS oil by mouth daily and injected with 10 mg/kg MTX IP weekly. Oral treatments were administered using a special curved smooth tip nontraumatic metal needle and IP injections were given for 3 weeks at days 7, 14 and 21. Animals were sacrificed at day 23. Malondialdehyde (MDA) and glutathione (GSH) measurements were performed on kidney homogenate. Histopathology of the kidneys were prepared and examined. MTX has resulted in a small elevation in MDA and reduction in GSH levels in kidney homogenate which was returned back to control values when NS and MTX were administered in combination. Statistical significance was achieved with elevation of GSH by MTX and NS compared to MTX alone. MTX caused histopathological changes suggesting nephrotoxicity in 6 animals out of 8, while no changes were found in all animals treated with MTX and NS. NS is protective against MTX-induced nephrotoxicity.

Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

PubMed Central

Chartier, Stephane R.; Thompson, Michelle L.; Longo, Geraldine; Fealk, Michelle N.; Majuta, Lisa A.; Mantyh, Patrick W.

2014-01-01

Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in non-healed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state. PMID:25196264

Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress.

PubMed

Liu, Tingting; Duan, Wang; Nizigiyimana, Paul; Gao, Lin; Liao, Zhouning; Xu, Boya; Liu, Lerong; Lei, Minxiang

2018-02-05

Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms. Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured. The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury. Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD.

PubMed

Ronzoni, Giacomo; Del Arco, Alberto; Mora, Francisco; Segovia, Gregorio

2016-08-01

Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure (1) on reactivity to novelty in an open-field (as an index of hyperarousal), and (2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86mA, and 6s per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to non-shocked animals during the first 5min in the open-field. In the amygdala, IFS animals showed an enhanced increase of noradrenaline induced by stress compared to control animals. Bilateral microinjections of propranolol (0.5μg) into the amygdala one hour before testing in the open-field normalized the decreased locomotion observed in IFS animals. On the other hand, bilateral microinjections of clenbuterol (30ng) into the amygdala of control animals did not change the exploratory activity induced by novelty in the open field. IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Observation of rat's colon polyps in real time by mini-endoscopy and raman spectroscopy

NASA Astrophysics Data System (ADS)

Andriana, Bibin Bintang; Mahardika, Anggara; Taketani, Akihiro; Sato, Hidetoshi

2018-02-01

Colorectal adenoma (CA) is a disease caused by various factors (such as genetic factors or environmental exposures). The appearance of colon polyp (CP) within colorectal might indicate the hint of CA development. Ball-lens hollow fiber Raman probe (BHRP) may has a high capability for detection of CA in living experimental animal and have already tested to rat's CP in this study, which was designed to collaborate between BHRP with mini-endoscopy to observe the biochemical alteration within normal colon tissue and rat's colon polyps in real time. BHRP and mini-endoscopy can distinguish the differences in their finger print spectra and make pictures the control and CP in the real time. At the first step, the real situation of normal colon and Rat's CP were washed by saline and observed with mini-endoscopy. BHRP was introduced to Dextran sodium sulphate (DSS)-induced Rat's CP to detect some of biochemical alteration. The main purpose of this study was to introduce mini-endoscopy to guide the BHRP for diagnosing of CP in real time and to compare it with spectra of normal colon (control group) in living rat. As the result, BHRP can provide the differences in band of control and CP group, which can inform that the biochemical of normal and CP has changed. As a major parameter to distinct normal and CP tissue were phosphatidylinositol, phosphodiester group, lipid, and collagen. Mini endoscopy and BHRP is very sensitive devices for diagnosing of CP in real time.

The effect of methylprednisolone on facial nerve paralysis with different etiologies.

PubMed

Yildirim, Mehmet Akif; Karlidag, Turgut; Akpolat, Nusret; Kaygusuz, Irfan; Keles, Erol; Yalcin, Sinasi; Akyigit, Abdulvahap

2015-05-01

The objective of this study was to evaluate the effectiveness of methylprednisolone (MP) in models of facial nerve paralysis obtained by nerve section, compression, or inoculation with herpes simplex virus (HSV). Experimental controlled animal study. Tertiary referral center. A total of 30 female New Zealand rabbits weighing 1200-3000 g were used for the study. They were randomly assigned to one of 6 groups of 5 animals each. A nerve section injury was realized in Groups 1a (section and MP) and 1b (section, control) rabbits. A compression-type injury was inflicted to rabbits in Groups 2a (compression and MP) and 2b (compression, control). As for animals in Groups 3a (Type 1 HSV and MP) and 3b (Type 1 HSV, controls), facial nerve paralysis resulting from viral infection was obtained. Animals in the 3 treatment groups, designated with the letter "a", were administered MP, 1 mg/kg/d, whereas those in control groups "b" received 1 mL normal saline, both during 3 weeks. All subjects were followed up for 2 months. At the end of this period, all animals had the buccal branch of the facial nerve excised on the operated side. Semi-thin sections of these specimens were evaluated under light microscopy for the following: perineural fibrosis, increase in collagen fibers, myelin degeneration, axonal degeneration, Schwann cell proliferation, and edema. No significant difference was observed (P > 0.05) between the MP treatment group and the control group with regard to perineural fibrosis, increase in collagen fibers, myelin degeneration, axonal degeneration, edema, or Schwann cell proliferation. In the group with a compressive lesion (Group 2), controls were no different from MP-treated animals as to perineural fibrosis, increase in collagen fibers, or Schwann cell proliferation, whereas axonal degeneration, myelin degeneration, and edema were significantly higher (P < 0.05) in the control group. When comparing the treatment and control groups among the animals inoculated with Type 1 HSV, no significant difference was found with regard to perineural fibrosis, axonal degeneration, myelin degeneration, or Schwann cell proliferation. The only statistically significant advantage of the treatment group was in edema formation (P < 0.05). As a result of the evaluation of MP efficacy in different models of facial nerve palsy, we may say that this drug was without effect on nerve healing in paralysis due to nerve section and that it only reduced nervous edema in paralysis induced by Type 1 HSV, whereas it had positive effects on healing in the type of paralysis caused by nerve compression.

50 CFR 14.107 - Conveyance.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

Behavioral effects of carbon monoxide on selected forest litter invertebrates

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

Kenyon, P.E.; Edgar, A.L.

1971-01-01

Man and higher vertebrates have been shown to be sensitive to CO in concentrations as low as 100 ppm. Various species of forest litter invertebrates were selected to investigate whether similar concentrations have deleterious effects on these animals. The animals were placed in various CO concentrations for a period of 7 weeks. Results indicated that all of the animals studied were found to spend long periods of time without moving. The animals studied were Oligochaeta, Gastropoda, Isopoda, Diplopoda, and Phalangida. Diplopod reactivity tests were performed and results for three individuals in air and three in 20% CO showed neither consistencymore » nor trend in reaction time. Eggs carried in brood pouches of several isopods hatched during the test period and the young emerged from the pouch. No difference in health and growth rate was observed between the control and any of the CO concentrations. Molting occurred frequently and normally in all chambers. Numerous activities were observed in the animals and no variation of behavior was detected which could be attributed to the presence of CO.« less

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

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

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

1982-03-01

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

THE INFLUENCE OF BIOTIN UPON SUSCEPTIBILITY TO MALARIA

PubMed Central

Trager, William

1943-01-01

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

Animal studies on Spacelab-3

NASA Technical Reports Server (NTRS)

Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.

1987-01-01

The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

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

PubMed Central

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

1980-01-01

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

Animal studies on Spacelab-3

NASA Technical Reports Server (NTRS)

Schatte, C.; Grindeland, R.; Callahan, P.; Funk, G.; Lencki, W.; Berry, W.

1986-01-01

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

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

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

Effects of hypertonic dextrose on injured rat skeletal muscles.

PubMed

Kunduracioglu, Burak; Ulkar, Bulent; Sabuncuoglu, Bizden T; Can, Belgin; Bayrakci, Kenan

2006-04-01

Histological examination of proliferative therapy effects on the healing process of muscular injury. We performed this study between March and August 2002 at Ankara University, School of Medicine, Laboratory of Animal Experiments, Ankara, Turkey. We used an experimental animal model by conducting a standardized cut injury of the gastrocnemius muscle in 30 adult male albino rats, which we divided into 2 groups; proliferative therapy group and control group. We evaluated the injured rat muscles by light microscopy on the fifth, eight, and twelfth day of injury. The muscular regeneration process began at day 5 in both the control and proliferative therapy groups. The proliferative therapy group revealed a prominent inflammatory reaction, fibroblast migration, and necrosis with accompanying regeneration and excessive connective tissue formation. We cannot consider proliferative therapy an appropriate treatment modality for muscular injuries, unless there is evidence of normal muscle physiology and biomechanics post traumatically.

Cyclic AMP system in muscle tissue during prolonged hypokinesia

NASA Technical Reports Server (NTRS)

Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

1980-01-01

Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

Eucalyptus globulus (Eucalyptus) Treatment of Candidiasis in Normal and Diabetic Rats

PubMed Central

Bokaeian, Mohammad; Nakhaee, Alireza; Moodi, Bita; Ali Khazaei, Hossein

2010-01-01

Background: The leaves of Eucalyptus globulus (eucalyptus) are used for treatment of diabetes mellitus in traditional medicine. The aim of this study was to evaluate the effects of eucalyptus in treatment of established systemic infection with Candida albicans in normal and streptozotocin-induced diabetic rats. Methods: Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected and randomly divided into six groups (n= 10): normal control, control + C. albicans, control + eucalyptus + C. albicans, diabetic control, diabetic + C. albicans, diabetic + eucalyptus + C. albicans. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and eucalyptus was added to the diet (62.5 g/kg) and drinking water (2.5 g/L) of treated animals for 4 weeks. The concerned groups were inoculated with C. albicans 15 days after diabetes induction. At the end of one month experiment, fasted rats were killed by cervical decapitation. Blood was collected from neck vein for estimation of glucose. C. albicans concentrations were estimated in liver and kidneys using serial dilution culture of tissue homogenates. Results: Eucalyptus administration significantly improved the hyperglycemia, polydipsia, polyphagia, and it also compensated weight loss of diabetic rats (P<0.05). Moreover, eucalyptus caused a significant reduction in C. albicans concentration in liver and kidney homogenates (P<0.01). Conclusion: The results revealed that eucalyptus improves Candidia infection in normal and diabetic rats that in some ways validates the traditional use of this plant in treatment of diabetic patients. PMID:21079663

Mechanical characterization of matrix-induced autologous chondrocyte implantation (MACI®) grafts in an equine model at 53 weeks.

PubMed

Griffin, Darvin J; Bonnevie, Edward D; Lachowsky, Devin J; Hart, James C A; Sparks, Holly D; Moran, Nance; Matthews, Gloria; Nixon, Alan J; Cohen, Itai; Bonassar, Lawrence J

2015-07-16

There has been much interest in using autologous chondrocytes in combination with scaffold materials to aid in cartilage repair. In the present study, a total of 27 animals were used to compare the performance of matrix-assisted chondrocyte implantation (MACI®) using a collagen sponge as a chondrocyte delivery vehicle, the sponge membrane alone, and empty controls. A total of three distinct types of mechanical analyses were performed on repaired cartilage harvested from horses after 53 weeks of implantation: (1) compressive behavior of samples to measure aggregate modulus (HA) and hydraulic permeability (k) in confined compression; (2) local and global shear modulus using confocal strain mapping; and (3) boundary friction coefficient using a custom-built tribometer. Cartilage defects receiving MACI® implants had equilibrium modulus values that were 70% of normal cartilage, and were not statistically different than normal tissue. Defects filled with Maix™ membrane alone or left empty were only 46% and 51-63% of control, respectively. The shear modulus of tissue from all groups of cartilage defects were between 4 and 10 times lower than control tissue, and range from 0.2 to 0.4 MPa. The average values of boundary mode friction coefficients of control tissue from all groups ranged from 0.42 to 0.52. This study represents an extensive characterization of the mechanical performance of the MACI® grafts implant in a large animal model at 53 weeks. Collectively, these data demonstrate a range of implant performance, revealing similar compressive and frictional properties to native tissue, with inferior shear properties. Copyright © 2015. Published by Elsevier Ltd.

On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock

PubMed Central

Errington, M. L.; e Silva, M. Rocha

1974-01-01

1. Long-lasting haemorrhagic hypotension (4·5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP9a), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP9a was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days. 2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock. 3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock. 4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period. 5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock. 6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period. 7. BPP9a had no measurable effect on the course of endotoxic shock. 8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed. PMID:4373570

Analysis of brief language tests in the detection of cognitive decline and dementia

PubMed Central

Radanovic, Marcia; Carthery-Goulart, Maria Teresa; Charchat-Fichman, Helenice; Herrera Jr., Emílio; Lima, Edson Erasmo Pereira; Smid, Jerusa; Porto, Cláudia Sellitto; Nitrini, Ricardo

2007-01-01

Lexical access difficulties are frequent in normal aging and initial stages of dementia.Verbal fluency tests are valuable to detect cognitive decline, evidencing lexico-semantic and executive dysfunction. Objectives To establish which language tests can contribute in detecting dementia and to verify schooling influence on subject performance. Method 74 subjects: 33 controls, 17 Clinical Dementia Rating (CDR) 0.5 and 24 (Brief Cognitive Battery - BCB e Boston Naming Test - BNT) 1 were compared in tests of semantic verbal fluency (animal and fruit), picture naming (BCB and BNT) and the language items of Mini Mental State Examination (MMSE). Results There were significant differences between the control group and both CDR 0.5 and CDR 1 in all tests. Cut-off scores were: 11 and 10 for animal fluency, 8 for fruit fluency (in both), 8 and 9 for BCB naming. The CDR 0.5 group performed better than the CDR 1 group only in animal fluency. Stepwise multiple regression revealed fruit fluency, animal fluency and BCB naming as the best discriminators between patients and controls (specificity: 93.8%; sensitivity: 91.3%). In controls, comparison between illiterates and literates evidenced schooling influence in all tests, except for fruit fluency and BCB naming. In patients with dementia, only fruit fluency was uninfluenced by schooling. Conclusion The combination of verbal fluency tests in two semantic categories along with a simple picture naming test is highly sensitive in detecting cognitive decline. Comparison between literate and illiterate subjects shows a lesser degree of influence of schooling on the selected tests, thus improving discrimination between low performance and incipient cognitive decline. PMID:29213366

Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation.

PubMed

Bai, S Y; Briggs, D I; Vickers, M H

2012-10-01

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life.

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

PubMed Central

Radostits, Otto M.; Littlejohns, Ian R.

1988-01-01

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

Hindlimb Immobilization in a Wheelchair Alters Functional Recovery Following Contusive Spinal Cord Injury in the Adult Rat

PubMed Central

Caudle, Krista L.; Brown, Edward H.; Shum-Siu, Alice; Burke, Darlene A.; Magnuson, Trystan S. G.; Voor, Michael J.; Magnuson, David S. K.

2015-01-01

Background Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. Objective To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Methods Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Results Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb–hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Conclusion Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries. PMID:21697451

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.

Uptake of yeast (Saccharomyces boulardii) in normal and rotavirus treated intestine.

PubMed Central

Cartwright-Shamoon, J; Dickson, G R; Dodge, J; Carr, K E

1996-01-01

BACKGROUND: There has recently been a growing interest in the use of the non-pathogenic yeast Saccharomyces boulardii, in the treatment of gastrointestinal disorders, including diarrhoea. The full effects of administration of the yeast are not fully understood. AIMS: To investigate the morphological effects of inoculated S boulardii on mouse intestinal villi, both in control animals and those treated with rotavirus. METHODS: Seven day old BALB/c seronegative mice were intubated with either rotavirus (30 microliters orally) or S boulardii (1.5 g/kg) or both rotavirus and S boulardii administered together. Control animals were given saline only. Animals were killed by decapitation 48 hours post-treatment. The middle region of the small intestine was studied using light microscopy and transmission and scanning electron microscopy, including backscattered electron imaging. RESULTS: Animals treated with rotavirus with or without S boulardii developed severe diarrhoea and showed morphological villous changes such as stromal separation and increased epithelial vacuolation. Specimens treated with S boulardii contained yeast particles within the mucosal tissues. CONCLUSION: The administration of S boulardii did not influence the changes produced by rotavirus, but yeast particles appeared to be taken up by the villous mucosa, with the predominant route apparently being uptake between adjacent epithelial cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8991857

Animal Study on Primary Dysmenorrhoea Treatment at Different Administration Times

PubMed Central

Pu, Bao-Chan; Fang, Ling; Gao, Li-Na; Liu, Rui; Li, Ai-zhu

2015-01-01

The new methods of different administration times for the treatment of primary dysmenorrhea are more widely used clinically; however, no obvious mechanism has been reported. Therefore, an animal model which is closer to clinical evaluation is indispensable. A novel animal experiment with different administration times, based on the mice oestrous cycle, for primary dysmenorrhoea treatment was explored in this study. Mice were randomly divided into two parts (one-cycle and three-cycle part) and each part includes five groups (12 mice per group), namely, Jingqian Zhitong Fang (JQF) 6-day group, JQF last 3-day group, Yuanhu Zhitong tablet group, model control group, and normal control group. According to the one-way ANOVAs, results (writhing reaction, and PGF2α, PGE2, NO, and calcium ions analysis by ELISA) of the JQF cycle group were in accordance with those of JQF last 3-day group. Similarly, results of three-cycle continuous administration were consistent with those of one-cycle treatment. In conclusion, the consistency of the experimental results illustrated that the novel animal model based on mice oestrous cycle with different administration times is more reasonable and feasible and can be used to explore in-depth mechanism of drugs for the treatment of primary dysmenorrhoea in future. PMID:25705236

Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

NASA Technical Reports Server (NTRS)

Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

1986-01-01

The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

A fermented soy permeate improves the skeletal muscle glucose level without restoring the glycogen content in streptozotocin-induced diabetic rats.

PubMed

Malardé, Ludivine; Vincent, Sophie; Lefeuvre-Orfila, Luz; Efstathiou, Théo; Groussard, Carole; Gratas-Delamarche, Arlette

2013-02-01

Exercise is essential into the therapeutic management of diabetic patients, but their level of exercise tolerance is lowered due to alterations of glucose metabolism. As soy isoflavones have been shown to improve glucose metabolism, this study aimed to assess the effects of a dietary supplement containing soy isoflavones and alpha-galactooligosaccharides on muscular glucose, glycogen synthase (GSase), and glycogen content in a type 1 diabetic animal model. The dietary supplement tested was a patented compound, Fermented Soy Permeate (FSP), developed by the French Company Sojasun Technologies. Forty male Wistar rats were randomly assigned to control or diabetic groups (streptozotocin, 45 mg/kg). Each group was then divided into placebo or FSP-supplemented groups. Both groups received by oral gavage, respectively, water or diluted FSP (0.1 g/day), daily for a period of 3 weeks. At the end of the protocol, glycemia was noticed after a 24-h fasting period. Glucose, total GSase, and the glycogen content were determined in the skeletal muscle (gastrocnemius). Diabetic animals showed a higher blood glucose concentration, but a lower glucose and glycogen muscle content than controls. Three weeks of FSP consumption allowed to restore the muscle glucose concentration, but failed to reduce glycemia and to normalize the glycogen content in diabetic rats. Furthermore, the glycogen content was increased in FSP-supplemented controls compared to placebo controls. Our results demonstrated that diabetic rats exhibited a depleted muscle glycogen content (-25%). FSP-supplementation normalized the muscle glucose level without restoring the glycogen content in diabetic rats. However, it succeeded to increase it in the control group (+20%).

Cathepsin B is not the processing enzyme for mouse prorenin.

PubMed

Mercure, Chantal; Lacombe, Marie-Josée; Khazaie, Khashayarsha; Reudelhuber, Timothy L

2010-05-01

Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.

Thrombus Degradation by Fibrinolytic Enzyme of Stenotrophomonas sp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats

PubMed Central

Tjandrawinata, Raymond R.

2016-01-01

Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats. PMID:27635131

9 CFR 313.2 - Handling of livestock.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

Mycoplasma and associated bacteria isolated from ovine pink-eye.

PubMed

Langford, E V

1971-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2004-10-01

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

The transgenic cloned pig population with integrated and controllable GH expression that has higher feed efficiency and meat production

PubMed Central

Ju, Huiming; Zhang, Jiaqing; Bai, Lijing; Mu, Yulian; Du, Yutao; Yang, Wenxian; Li, Yong; Sheng, Anzhi; Li, Kui

2015-01-01

Sustained expression of the GH gene has been shown to have detrimental effects on the health of animals. In the current study, transgenic founder pigs, with controllable pig growth hormone (pGH) expression, were cloned via the handmade cloning method (HMC), and pGH expression levels were examined at the cellular and organismal levels. The serum pGH levels in 3 founder male pigs were found to be significantly higher after induction with intramuscular injection of doxycycline (DOX) compared to baseline. A daily dose of DOX was administered via feed to these animals for a period of 65 to 155 days. The growth rate, feed efficiency and pGH serum concentration increased in the DOX-induced transgenic group compared with the other groups. 8 numbers of animals were euthanized and the dressing percentage, loin muscle and lean meat percentage were significantly higher in the DOX-induced F1 transgenic group compared with the other groups. In this study a large population of transgenic pigs, with integrated controllable expression of a transgene, was obtained. The transgenic pigs were healthy and normal in terms of reproductive capability. At the same time, feed efficiency was improved, production processes were accelerated and meat yield was increased. PMID:25959098

The transgenic cloned pig population with integrated and controllable GH expression that has higher feed efficiency and meat production.

PubMed

Ju, Huiming; Zhang, Jiaqing; Bai, Lijing; Mu, Yulian; Du, Yutao; Yang, Wenxian; Li, Yong; Sheng, Anzhi; Li, Kui

2015-05-11

Sustained expression of the GH gene has been shown to have detrimental effects on the health of animals. In the current study, transgenic founder pigs, with controllable pig growth hormone (pGH) expression, were cloned via the handmade cloning method (HMC), and pGH expression levels were examined at the cellular and organismal levels. The serum pGH levels in 3 founder male pigs were found to be significantly higher after induction with intramuscular injection of doxycycline (DOX) compared to baseline. A daily dose of DOX was administered via feed to these animals for a period of 65 to 155 days. The growth rate, feed efficiency and pGH serum concentration increased in the DOX-induced transgenic group compared with the other groups. 8 numbers of animals were euthanized and the dressing percentage, loin muscle and lean meat percentage were significantly higher in the DOX-induced F1 transgenic group compared with the other groups. In this study a large population of transgenic pigs, with integrated controllable expression of a transgene, was obtained. The transgenic pigs were healthy and normal in terms of reproductive capability. At the same time, feed efficiency was improved, production processes were accelerated and meat yield was increased.

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

Alterations of red blood cell sodium transport during malarial infection

PubMed Central

Dunn, Michael J.

1969-01-01

Previous studies have suggested that malaria induces changes in erythrocytic membrane permeability and susceptibility to osmotic lysis. The present study investigated erythrocytic transport of sodium with cells from Rhesus monkeys infected with Plasmodium knowlesi. Red blood cell sodium concentration was significantly elevated in 37 parasitized animals (21.8±1.2 mM; mean ±SEM), as compared to 23 control animals (10.0±0.38 mM). The cellular sodium increased with the density of parasitemia and the cellular potassium decreased in proportion to the elevation of sodium. Nonparasitized as well as parasitized erythrocytes possessed this abnormality of cation metabolism. Effective chloroquine therapy reversed the changes over a period of 4 days. Active sodium outflux rate constants were depressed in animals with malaria (0.202±0.012), as compared to controls (0.325±0.027). Passive sodium influx rate constants were higher in infected monkeys (0.028±0.002) than in control animals (0.019±0.002). The cross incubation of malarial plasma with normal red blood cells induced a 22% diminution in active sodium outflux but no changes were observed in sodium influx. It is concluded that malaria alters erythrocytic sodium transport in all erythrocytes. The elevated intracellular sodium concentration is the net result of decreased sodium outflux and increased sodium influx. The plasmodium organism or the affected host may produce a circulating substance that is deleterious to erythrocytic membrane cation transport. PMID:4975361

Silk fibroin hydrogel as physical barrier for prevention of post hernia adhesion.

PubMed

Konar, S; Guha, R; Kundu, B; Nandi, S; Ghosh, T K; Kundu, S C; Konar, A; Hazra, S

2017-02-01

Adhesion formation remains a major complication following hernia repair surgery. Physical barriers though effective for adhesion prevention in clinical settings are associated with major disadvantages, therefore, needs further investigation. This study evaluates silk fibroin hydrogel as a physical barrier on polypropylene mesh for the prevention of adhesion following ventral hernia repair. Peritoneal explants were cultured on silk fibroin scaffold to evaluate its support for mesothelial cell growth. Full thickness uniform sized defects were created on the ventral abdominal wall of rabbits, and the defects were covered either with silk hydrogel coated polypropylene mesh or with plain polypropylene mesh as a control. The animals were killed after 1 month, and the adhesion formation was graded; healing response of peritoneum was evaluated by immunohistochemistry with calretinin, collagen staining of peritoneal sections, and expression of PCNA, collagen-I, TNFα, IL6 by real time PCR; and its adverse effect if any was determined. Silk fibroin scaffold showed excellent support for peritoneal cell growth in vitro and the cells expressed calretinin. A remarkable prevention of adhesion formation was observed in the animals implanted with silk hydrogel coated mesh compared to the control group; in these animals peritoneal healing was complete and predominantly by mesothelial cells with minimum fibrotic changes. Expression of inflammatory cytokines decreased compared to control animals, histology of abdominal organs, haematological and blood biochemical parameters remained normal. Therefore, silk hydrogel coating of polypropylene mesh can improve peritoneal healing, minimize adhesion formation, is safe and can augment the outcome of hernia surgery.

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

PubMed

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

2017-11-01

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

Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease

PubMed Central

Barkow, Jessica Cummiskey; Freed, Curt R.

2017-01-01

Exercise has been recommended to improve motor function in Parkinson patients, but its value in altering progression of disease is unknown. In this study, we examined the neuroprotective effects of running wheel exercise in mice. In adult wild-type mice, one week of running wheel activity led to significantly increased DJ-1 protein concentrations in muscle and plasma. In DJ-1 knockout mice, running wheel performance was much slower and Rotarod performance was reduced, suggesting that DJ-1 protein is required for normal motor activity. To see if exercise can prevent abnormal protein deposition and behavioral decline in transgenic animals expressing a mutant human form of α-synuclein in all neurons, we set up running wheels in the cages of pre-symptomatic animals at 12 months old. Activity was monitored for a 3-month period. After 3 months, motor and cognitive performance on the Rotarod and Morris Water Maze were significantly better in running animals compared to control transgenic animals with locked running wheels. Biochemical analysis revealed that running mice had significantly higher DJ-1, Hsp70 and BDNF concentrations and had significantly less α-synuclein aggregation in brain compared to control mice. By contrast, plasma concentrations of α-synuclein were significantly higher in exercising mice compared to control mice. Our results suggest that exercise may slow the progression of Parkinson’s disease by preventing abnormal protein aggregation in brain. PMID:29272304

Systemic immunity influences hearing preservation in cochlear implantation.

PubMed

Souter, Melanie; Eastwood, Hayden; Marovic, Paul; Kel, Gordana; Wongprasartsuk, Sarin; Ryan, Allen F; O'Leary, Stephen John

2012-06-01

To determine whether a systemic immune response influences hearing thresholds and tissue response after cochlear implantation of hearing guinea pigs. Guinea pigs were inoculated with sterile antigen (Keyhole limpet hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem response thresholds were performed before implantation and 1 and 4 weeks later. Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid carboxymethylcellulose sponge and was applied to the round window for 30 minutes before electrode insertion. Normal saline was used for controls. Cochlear histology was performed at 4 weeks after implantation to assess the tissue response to implantation. To control for the effect of keyhole limpet hemocyanin priming, a group of unprimed animals underwent cochlear implantation with a saline-soaked pledget applied to the round window. Keyhole limpet hemocyanin priming had no significant detrimental effect on thresholds without implantation. Thresholds were elevated after implantation across all frequencies tested (2-32 kHz) in primed animals but only at higher frequencies (4-32 kHz) in unprimed controls. In primed animals, dexamethasone treatment significantly reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the more frequent observation of lymphocytes in the tissue response to the implant. Systemic immune activation at the time of cochlear implantation broadened the range of frequencies experiencing elevated thresholds after implantation. Local dexamethasone provides partial protection against this hearing loss, but the degree and extent of protection are less compared to previous studies with unprimed animals.

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats.

PubMed

Alabi, A S; Omotoso, Gabriel O; Enaibe, B U; Akinola, O B; Tagoe, C N B

2013-03-01

This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. THE ANIMALS USED FOR THE STUDY WERE GROUPED INTO THREE: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions.

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

PubMed Central

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

1978-01-01

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

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

PubMed Central

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

1982-01-01

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

Endoreplication and polyploidy: insights into development and disease

PubMed Central

Fox, Donald T.; Duronio, Robert J.

2013-01-01

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

Toxic Hazards Research Unit - 1988

DTIC Science & Technology

1989-07-01

and control groups, and all group means for these parameters were within the normal range for the age and species of test animals used (Wolford et al...13 APPENDIX 1 DRAIZEa SCALE FOR SCALING OCULAR LESIONS Parameter Score 1. Cornea A Opacity degree of density (area most taken for reading) No opacity...Therap 32 377 390 14 APPENDIX 2 DRAIZEa SCALE FOR EVALUATING AND SCORING SKIN REACTIONS Parameter Score 1. Erythema No erythema 0 Very slight erythema

Control of Dermatomycoses by Physical, Chemical and Biological Agents.

DTIC Science & Technology

1978-10-31

converts susceptible hyphae to resistant arthrospores. 4. Arthrospores are full y capable of germinating into infectious hyphae by the normal skin ...dried (most physicians advise to keep the lesions as dry as possible!) skin lesions is a futile attempt . This approach will be tested in an animal n...distilled water three times by means of centrl fugation (1 ,500 x r, 15 mm ). In some experiments , young hyphae or ar~hrosporu1ating

Quantum control of the normal modes of benzene with ultrafast laser pulses

NASA Astrophysics Data System (ADS)

Sauer, Petra; Dou, Yusheng; Torralva, Ben; Allen, Roland

2005-03-01

Remarkable innovations in laser technology have made it possible to create laser pulses with ultrashort durations (below 100 femtoseconds) and ultrahigh intensities (above 1 terawatt per cm^2). To understand the behavior of complex molecules and materials in this new regime of physics, chemistry, biology, and materials science requires innovative techniques which complement experiment and standard theory, and which can treat situations in which conventional approximations like the Born- Oppenheimer approximation, the Franck-Condon principle, and Fermi's golden rule are no longer valid. In this talk we describe a method that we are developing, semiclassical electron-radiation-ion dyanmics (SERID), which can be used to perform simulations of the coupled dynamics of electrons and nuclei in an intense radiation field. We have employed this technique in studying the normal modes of benzene, and the possibility of controlling these modes by optimizing the laser pulses that are applied to the molecule. Animations will be shown of particular normal modes, including the breathing and beating modes, illustrating their symmetries and other properties, and of the photodissociation of benzene when the laser pulse exceeds a threshold intensity.

Experiment K-313: Rat and quail ontogenesis

NASA Technical Reports Server (NTRS)

Keefe, J. R.

1981-01-01

The potential effects of spaceflight on the processes of mammalian fertilizaton, implantation and embryonic development are investigated. Five female and two male rats were placed together on Day 2 of the flight. By R+17, it was determined that both flight and synchronous females were not carrying normal pregnancies and three of the flight animals were laparotomized. The uterus and ovaries were processed for microscopic analyses. The two remaining flight females were allowed to recover from the exploratory operation, rebred with flight males and delivered normal litters. As a control for potential transplacental effects that might be interpreted as direct spaceflight effects, a series of fertilized Japanese quail (Coturnix japonica) eggs was flown on Cosmos 1129. Although all of the eggs were adversely impacted by an inflight failure of the incubator humidifier on flight Day 13, several embryos were able to progress to a developmental stage equivalent to that of a control 10-12 Day embryo.

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

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

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2010-05-01

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

Effect of methanolic extract of Musa sapientum leaves on gastrointestinal transit time in normal and alloxan induced diabetic rats: possible mechanism of action.

PubMed

Adewoye, E O; Ige, A O; Latona, C T

2011-11-23

Disorders of gastrointestinal motility have been associated with diabetes mellitus. Hyperglycaemia particularly has been reported to inhibit gastrointestinal transit time while glibenclamide, a sulphonylurea and insulin, both increased transit time. Musa sapientum has also been reported as an antidiabetic agent but there is dearth of information on the effect of this plant on gastrointestinal motility. This study was therefore carried out to investigate the effect of methanolic extract of Musa sapientum leaves (MEMSL) on gastrointestinal transit time (GITT) in male albino rats with and without hyperglycaemia and to elucidate possible mechanism by which this extract functions. Fifty five albino rats were divided into 11 groups of five animals each. All animals were fasted for 24hrs before the begining of the experiment. Group 1 served as control; while the remaining groups (2 - 11) were treated with 250mg/kg; 500mg/kg MEMSL; diabetic control; diabetic treated with 250mg/kg; 500mg/kg MEMSL; diabetic treated with glibenclamide (5mg/kg); normal rats treated with nifedipine (50mg/kg); normal rats treated with calcium chloride (CaCl2) only (10mg/kg); groups 10 and 11 were both pretreated with CaCl2 and subsequently treated with 250mg/kg and 500mg/kg MEMSL respectively. All plant extracts used for treatments were dissolved in normal saline and administered orally using orogastric tube. Charcoal meal was used as marker in the estimation of GITT. The study showed significant decrease in GITT in the normal rats treated with 250mg/kg and 500mg/kg of extract. However, in the diabetic rats treated with 500mg/kg MEMSL, there was significant increase in GITT and this is comparable with the gut response to glibenclamide (5mg/kg). Musa sapientum extract produced significant decrease in transit time in the calcium chloride pre-treated normal rats and this is comparable to the effect observed in Nifedipine treated group. The significant reduction in GITT produced by MEMSL in the normal rats reflects a strong possibility of MEMSL acting as calcium channel antagonist through the voltage gated calcium channel which may be due to the presence of alkaloids, saponins, cardenolides. There is the possibility of the extract acting as an inhibitor of potassium channel at higher concentration as observed in glibenclamide treated groups.

Effects of Selective and Non-Selective Glucocorticoid Receptor II Antagonists on Rapid-Onset Diabetes in Young Rats

PubMed Central

Beaudry, Jacqueline L.; Dunford, Emily C.; Teich, Trevor; Zaharieva, Dessi; Hunt, Hazel; Belanoff, Joseph K.; Riddell, Michael C.

2014-01-01

The blockade of glucocorticoid (GC) action through antagonism of the glucocorticoid receptor II (GRII) has been used to minimize the undesirable effects of chronically elevated GC levels. Mifepristone (RU486) is known to competitively block GRII action, but not exclusively, as it antagonizes the progesterone receptor. A number of new selective GRII antagonists have been developed, but limited testing has been completed in animal models of overt type 2 diabetes mellitus. Therefore, two selective GRII antagonists (C113176 and C108297) were tested to determine their effects in our model of GC-induced rapid-onset diabetes (ROD). Male Sprague-Dawley rats (∼ six weeks of age) were placed on a high-fat diet (60%), surgically implanted with pellets containing corticosterone (CORT) or wax (control) and divided into five treatment groups. Each group was treated with either a GRII antagonist or vehicle for 14 days after surgery: CORT pellets (400 mg/rat) + antagonists (80 mg/kg/day); CORT pellets + drug vehicle; and wax pellets (control) + drug vehicle. After 10 days of CORT treatment, body mass gain was increased with RU486 (by ∼20% from baseline) and maintained with C113176 administration, whereas rats given C108297 had similar body mass loss (∼15%) to ROD animals. Fasting glycemia was elevated in the ROD animals (>20 mM), normalized completely in animals treated with RU486 (6.2±0.1 mM, p<0.05) and improved in animals treated with C108297 and C113176 (14.0±1.6 and 8.8±1.6 mM, p<0.05 respectively). Glucose intolerance was normalized with RU486 treatment, whereas acute insulin response was improved with RU486 and C113176 treatment. Also, peripheral insulin resistance was attenuated with C113176 treatment along with improved levels of β-cell function while C108297 antagonism only provided modest improvements. In summary, C113176 is an effective agent that minimized some GC-induced detrimental metabolic effects and may provide an alternative to the effective, but non-selective, GRII antagonist RU486. PMID:24642683

Alleviation of response suppression to conditioned aversive stimuli by lesions of the dorsal noradrenergic bundle.

PubMed

Tsaltas, E; Gray, J A; Fillenz, M

1984-08-01

Rats with neurotoxic lesions of the dorsal ascending noradrenergic bundle (DB) were compared with sham-operated (SH) controls on the acquisition, steady state and extinction of response suppression maintained by a classical (conditioned suppression) or an instrumental (discriminated punishment) contingency. DB lesions interfered neither with the acquisition of the reference response of sucrose-rewarded barpressing nor with unconditioned responding to the overhead flashing light subsequently used as a signal of shock. The acquisition of discriminated response suppression was also unaffected by the lesion under both types of contingency. However, once discriminated suppression had stabilized, both the conditioned and the discriminative stimulus used were significantly less effective in maintaining suppression in DB animals than in SH controls provided that low intensity footshock (0.2 mA) was used as the unconditioned stimulus (UCS). Upon increase of UCS intensity (to 0.5 mA) normal suppression was observed in the DB group under both contingencies. Extinction of the classical contingency reinstated the difference between DB and SH performance: DB lesion resulted in significantly faster extinction of fear. In contrast, extinction of the discriminated punishment contingency was unaffected by the lesion, although generalized response suppression dissipated faster in the DB than in the SH animals trained under this condition. Our results offer no support for the reinforcement hypothesis of DB function (normal acquisition of barpressing and of discriminated suppression of barpressing); mixed support (greater initial generalization of suppression in DB animals) and contradiction (more rapid extinction of conditioned suppression in DB animals) for the attentional hypothesis; and weak support (reduced suppression and more rapid extinction of suppression in DB animals, but only within limited experimental parameters) for the anxiety hypothesis of DB function. Hence none of the extant theories of DB function offer a ready explanation of the pattern of results presented here. A simple interpretation which conforms with the sparsity of positive behavioural findings in the literature on DB lesions is that forebrain noradrenaline contributes to the detection and utilization of conditioned stimuli; but that this contribution is critical only for the detection of stimuli with low associative strength.

Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.

PubMed

Lambert, C S; Philpot, R M; Engberg, M E; Johns, B E; Wecker, L

2015-09-15

Studies have demonstrated that administration of the neuronal nicotinic receptor agonist varenicline to rats with olivocerebellar lesions attenuates balance deficits on a rotorod and balance beam, but the effects of this drug on gait deficits have not been investigated. To accomplish this, male Sprague-Dawley rats were trained to walk on a motorized treadmill at 25 and 35 cm/s and baseline performance determined; both temporal and spatial gait parameters were analyzed. A principal component analysis (PCA) was used to identify the key components of gait, and the cumulative gait index (CGI) was calculated, representing deviations from prototypical gait patterns. Subsequently, animals either remained as non-lesioned controls or received injections of 3-acetylpyridine (3-AP)/nicotinamide to destroy the climbing fibers innervating Purkinje cells. The gait of the non-lesioned group was assessed weekly to monitor changes in the normal population, while the gait of the lesioned group was assessed 1 week following 3-AP administration, and weekly following the daily administration of saline or varenicline (0.3, 1.0, or 3.0mg free base/kg) for 2 weeks. Non-lesioned animals exhibited a 60-70% increased CGI over time due to increases in temporal gait measures, whereas lesioned animals exhibited a nearly 3-fold increased CGI as a consequence of increases in spatial measures. Following 2 weeks of treatment with the highest dose of varenicline (3.0mg free base/kg), the swing duration of lesioned animals normalized, and stride duration, stride length and step angle in this population did not differ from the non-lesioned population. Thus, varenicline enabled animals to compensate for their impairments and rectify the timing of the gait cycle. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-08-01

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

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

PubMed

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

1998-08-01

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

Light and water are not simple conditions: fine tuning of animal housing in male C57BL/6 mice.

PubMed

Langgartner, Dominik; Foertsch, Sandra; Füchsl, Andrea M; Reber, Stefan O

2017-01-01

While animal housing conditions are highly controlled and standardized between different laboratories, there are still many subtle differences that unavoidably influence the host organisms and, consequently, interlaboratory reproducibility. Here, we investigated the physiological and immunological consequences between two light/dark cycle (LDC) lengths (14-h/10-h vs. 12-h/12-h LDC) and two commonly used forms of drinking water (acidified drinking water (AW) versus normal tap water (NW)) in single-housed (SH) mice. Our results indicate that SH mice bred under a 12-h/12-h LDC and NW at the supplier's facility showed increased basal morning plasma corticosterone (CORT) levels even 4 weeks after arrival at our animal facility employing a 14-h/10-h LDC and AW. This effect was even more pronounced two weeks after arrival and had abated after 8 weeks. In agreement, increased plasma adrenocorticotropic hormone (ACTH), adrenal in vitro ACTH sensitivity, as well as relative and absolute adrenal weight normalized during this 8-week exposure to the novel and unfamiliar 14-h/10-h LDC and AW. Employment of a 12-h/12-h LDC in our facility completely abrogated the CORT-elevating effects of the 14-h/10-h LDC, despite these animals drinking AW. When both the water and light conditions were matched to those at the supplier's facility, we observed a further reduction in adrenal weight, increased thymus weight, and decreased pro-inflammatory cytokine secretion of isolated and anti-CD3/28-stimulated mesenteric lymph node cells. In summary, our results indicate that prolonged alteration of both the light phase and drinking water represent severe and long-lasting stressors for laboratory rodents. These findings are of general interest for all scientists obtaining their experimental animals from conventional suppliers.

[Neuroprotective effect of erigeron breviscapus (vant) hand-mazz on NMDA-induced retinal neuron injury in the rats].

PubMed

Shi, Jingming; Jiag, Youqin; Liu, Xuyang

2004-07-01

To investigate if Erigeron Breviscapus (vant) Hand-Mazz (EBHM) has a neuroprotective effect against NMDA-induced neuron death in retinal ganglion cell layer (RGCL). Sixty healthy SD rats were randomly divided into four groups. 6 animals were in normal control group (group A). The others were divided as group B (EBHM group), group C (normal saline+NMDA group), group D (EBHM+NMDA group). Each group has 18 rats. 10 nmol NMDA was chosen for intravitreal injection to cause partial damage of the neurons in RGCL in the right eyes of Groups C and D. Same volume PBS was intravitreal injected in the left eyes as self-control. Groups B and D were pre-treated intraperitoneally with 6% EBHM solution at a dose of 15 mg x 100 g(-1) x d(-1) seven days before and after NMDA treatment. Group C were administrated intraperitoneally with 0.9% normal saline at the same time of EBHM injection. Rats were sacrificed in 4, 7, 14 days after NMDA treatment. Flat preparation of whole retinas were stained with 0.5% cresyl violet and neuron counting in RGCL from both eyes. Each subgroup has 6 rats. There was no significant difference between the right eye and the left eye of neuron counting from RGCL in normal control group (group A) (P=0.200). There was no significant difference between normal control group and EBHM group either in the right eyes or in the left eye in 4 days, 7 days and 14 days respectively after intravitreal injection of 10 nmol NMDA in group C and group D. (P=0.636, P=0.193). Neuron counting from RGCL of group C and group D were significant decreased in the NMDA-treated eyes in 4 days, 7 days and 14 days after intravitreal injection (P < 0.001). There ws no significant difference between self-control eyes and normal control group (P > 0.05). Neuron counting was significantly higher in the EBHM+NMDA group than normal saline+NMDA group at 14 days after intraviteal injection (P=0.044). However,it is obvious that the difference was still significant between normal control group and EBHM+NMDA group (P < 0.05). EBHM has no effect on neuron counting of RGCL when administered alone in normal rats. It is suggested that EBHM has partial protective effect on NMDA-induced neuron loss in RGCL in the rat.

Cerebroprotective effect of combined treatment with pyrazidol and bemitil in craniocerebral trauma.

PubMed

Zarubina, I V; Kuritsyna, N A; Shabanov, P D

2004-07-01

Monotherapy of consequences of craniocerebral trauma with pyrazidol (1 mg/kg) produced an anxiolytic effect in animals highly resistant to hypoxia and activating effect on low resistant animals. Treatment with bemitil in a dose of 25 mg/kg produced a cerebroprotective effect and normalized individual behavioral characteristics, parameters of energy metabolism, and state of the antioxidant system in the brain of highly and low resistant rats. The effect of bemitil was most pronounced in highly resistant animals. During combined treatment, pyrazidol and bemitil had an additive effect in animals of both groups. They normalized behavioral reactions and prevented the development of metabolic disturbances in the brain.

Long term imaging of living brain cancer cells

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Acute coenurosis of dairy sheep from 11 flocks in Greece.

PubMed

Giadinis, N D; Psychas, V; Polizopoulou, Z; Papadopoulos, E; Papaioannou, N; Komnenou, A Th; Thomas, A-L; Petridou, E J; Kritsepi-Konstantinou, M; Lafi, S Q; Brellou, G D

2012-07-01

A syndrome of acute neurological dysfunction with increased mortality was observed in lambs of 10 dairy sheep flocks and adult animals in one flock in Central and Northern Greece. Each farmer completed a questionnaire regarding the management and feeding of their flocks. In seven of the 11 flocks the affected animals were grazing pasture, while in the remaining four flocks (5, 8, 9, 10) the animals were fed alfalfa hay (Medicago sativa) and concentrates indoors. A follow-up study of the affected flocks was conducted during the next 12 months. Of 42 sheep with acute coenurosis that were examined, the most prominent neurological abnormalities were ataxia, depression, blindness, scoliosis, coma and dysmetria. Except for the four sheep that were comatose, all other animals had normal body temperatures and their appetites remained normal or were slightly decreased. Haematological findings of 15 examined sheep were within normal limits. The affected sheep were subject to euthanasia. A histopathological examination was performed in 13 cases. Faecal samples from dogs associated with these flocks were negative for taeniid infections. During the following 12 months cases of chronic coenurosis in these flocks were observed. In the 42 animals that were necropsied, the main gross findings were cystic formations between 0.5-1 cm in diameter with translucent walls that were seen lying free on the leptomeninges or partly penetrating the brain tissue, sterile microabscecess and brain necrosis. Histopathological evaluation of tissue sections of 13 brains showed multifocal purulent or pyogranulomatous meningoencephalitis, accompanied by eosinophilic infiltrations. No bacteria were isolated following bacterial culture of brain tissue Parasitological examination of the cysts from five cases revealed whitish specks on the transparent cyst wall and germination membrane representing the scolices. Acute coenurosis was diagnosed in all cases studied. Acute coenurosis can be one of the causes of acute encephalopathy mainly in lambs, but also in adult sheep. This condition is incurable, but can be controlled by changing the feeding regime. Cases of chronic coenurosis may be seen a few months later in the same flock.

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

NASA Astrophysics Data System (ADS)

Horn, Eberhard R.

2000-01-01

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

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

PubMed

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

2016-01-01

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

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance.

PubMed

Stevanovic, Darko; Starcevic, Vesna; Vilimanovich, Urosh; Nesic, Dejan; Vucicevic, Ljubica; Misirkic, Maja; Janjetovic, Kristina; Savic, Emina; Popadic, Dusan; Sudar, Emina; Micic, Dragan; Sumarac-Dumanovic, Mirjana; Trajkovic, Vladimir

2012-01-01

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1β, IFN-γ) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1β, IL-6, IFN-γ, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-β remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 μg/day) for five consecutive days significantly reduced TNF, IL-1β and IFN-γ levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of IFN-γ, IL-17, IL-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs

PubMed Central

Chiaro, Joseph A; O’Donnell, Patricia; Shore, Eileen M; Malhotra, Neil R; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2014-01-01

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kypho-scoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT+SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT treated; and MPS I ERT+SIM treated. Animals were euthanized at one year-of-age. Intervertebral disc condition and spinal cord compression were evaluated from MRIs and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using microcomputed tomography, and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT+SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, while ERT treatment resulted in partial preservation of these properties. ERT+SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone. PMID:24898323

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

PubMed

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

1985-06-01

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

A deletion mutation in bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle

PubMed Central

2010-01-01

Background Osteopetrosis is a skeletal disorder of humans and animals characterized by the formation of overly dense bones, resulting from a deficiency in the number and/or function of bone-resorbing osteoclast cells. In cattle, osteopetrosis can either be induced during gestation by viral infection of the dam, or inherited as a recessive defect. Genetically affected calves are typically aborted late in gestation, display skull deformities and exhibit a marked reduction of osteoclasts. Although mutations in several genes are associated with osteopetrosis in humans and mice, the genetic basis of the cattle disorder was previously unknown. Results We have conducted a whole-genome association analysis to identify the mutation responsible for inherited osteopetrosis in Red Angus cattle. Analysis of >54,000 SNP genotypes for each of seven affected calves and nine control animals localized the defective gene to the telomeric end of bovine chromosome 4 (BTA4). Homozygosity analysis refined the interval to a 3.4-Mb region containing the SLC4A2 gene, encoding an anion exchanger protein necessary for proper osteoclast function. Examination of SLC4A2 from normal and affected animals revealed a ~2.8-kb deletion mutation in affected calves that encompasses exon 2 and nearly half of exon 3, predicted to prevent normal protein function. Analysis of RNA from a proven heterozygous individual confirmed the presence of transcripts lacking exons 2 and 3, in addition to normal transcripts. Genotyping of additional animals demonstrated complete concordance of the homozygous deletion genotype with the osteopetrosis phenotype. Histological examination of affected tissues revealed scarce, morphologically abnormal osteoclasts displaying evidence of apoptosis. Conclusions These results indicate that a deletion mutation within bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle. Loss of SLC4A2 function appears to induce premature cell death, and likely results in cytoplasmic alkalinization of osteoclasts which, in turn, may disrupt acidification of resorption lacunae. PMID:20507629

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

9 CFR 55.3 - Appraisal and destruction of captive cervids.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

Effects of condensed tannin from Acacia mearnsii on sheep infected naturally with gastrointestinal helminthes.

PubMed

Cenci, F B; Louvandini, H; McManus, C M; Dell'Porto, A; Costa, D M; Araújo, S C; Minho, A P; Abdalla, A L

2007-03-15

The effect of tannins on endoparasite control in hair sheep was investigated using 20 entire lambs of the Santa Inês breed. At the beginning of the experiment these animals were 6-months old and weighed 22.5kg+/-4.7. The treatments used were (10 animals each): GT (animals receiving 18g of Acácia negra containing 18% of condensed tannin/animal/week) and GC (animals not receiving tannin). The experiment lasted 84 days, with animals kept on an Andropogon gayanus pasture. Faeces were collected weekly, with weighing and blood collection carried out fortnightly. At slaughter, the adult worms were harvested for identification and counting. Although the GT animals weighed more than the GC lambs at slaughter, these differences were not significant (P>0.05). In general, the values for haemoglobin, hematocrit, total protein, urea, phosphorus and calcium in the serum were within normal levels and no significant differences between groups were observed. For faecal egg count (FEC), lower values were observed throughout the experiment in the group receiving tannin, but these differences were only significant in the eighth week. There was a lower output of eggs by regression for GT compared with GC (P<0.05). The species identified, in decreasing order of worm count, were: Trichostrongylus colubriformis, Haemonchus contortus, Oesophagostomum columbianum, Cooperia sp., Strongyloides papillosus, Trichuris globulosa and Moniezia expansa. The total worm count and number of each species of worm were lower for GT compared with GC for T. colubriformis and Cooperia sp. (P<0.05). Condensed tannin (CT) from A. negra had an antiparasitic effect, thereby representing an alternative for worm control in sheep.

Horses Helping Children Grow

ERIC Educational Resources Information Center

Graham, Louise B.; Lindsey, Allison

2017-01-01

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

The Kölliker-Fuse nucleus: a review of animal studies and the implications for cranial nerve function in humans.

PubMed

Browaldh, Nanna; Bautista, Tara G; Dutschmann, Mathias; Berkowitz, Robert G

2016-11-01

To review the scientific literature on the relationship between Kölliker-Fuse nucleus (KF) and cranial nerve function in animal models, with view to evaluating the potential role of KF maturation in explaining age-related normal physiologic parameters and developmental and acquired impairment of cranial nerve function in humans. Medical databases (Medline and PubMed). Studies investigating evidence of KF activity responsible for a specific cranial nerve function that were based on manipulation of KF activity or the use of neural markers were included. Twenty studies were identified that involved the trigeminal (6 studies), vagus (9), and hypoglossal nerves (5). These pertained specifically to a role of the KF in mediating the dive reflex, laryngeal adductor control, swallowing function and upper airway tone. The KF acts as a mediator of a number of important functions that relate primarily to laryngeal closure, upper airway tone and swallowing. These areas are characterized by a variety of disorders that may present to the otolaryngologist, and hence the importance of understanding the role played by the KF in maintaining normal function.

Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

PubMed Central

Heberlein, Andrea S.; Adolphs, Ralph

2004-01-01

Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

Antihyperlipidemic Effects of Sour Cherries Characterized by Different In Vitro Antioxidant Power and Polyphenolic Composition.

PubMed

Papp, Nóra; Blázovics, Anna; Fébel, Hedvig; Salido, Sofía; Altarejos, Joaquín; Fehér, Erzsébet; Kocsis, Ibolya; Szentmihályi, Klára; Abrankó, László; Hegedűs, Attila; Stefanovits-Bányai, Éva

2015-12-01

The aims of the present study were to clarify in vivo effects of three sour cherry cultivars characterized by different polyphenolic composition in hyperlipidemic animals in a short term experiment. The three different sour cherry cultivars were chosen based on their total in vitro antioxidant capacity, total polyphenolic, monomeric anthocyanin and flavonoid content. Male Wistar rats were divided randomly into eight groups: rats kept on normal diet (control) and normal diet supplied with sour cherry powder of one of the three cultivars; others were kept on fat-rich diet and fat-rich diet supplied with sour cherry powder prepared from one of the three cultivars. The treatment lasted 10 days. Lyophilized sour cherry administered in the diet decreased both total cholesterol and LDL cholesterol levels, and increased the HDL cholesterol concentration in sera of hyperlipidemic animals. Significant differences were found in the efficacy of different sour cherry cultivars in case of hyperlipidemia. Sour cherries characterized by higher polyphenol content seem to have a more pronounced effect on serum cholesterol levels. Our results suggest that besides anthocyanins, colourless polyphenols also have lipid lowering effect.

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

PubMed

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

2018-05-16

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

Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

PubMed

Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

2008-02-01

The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel.

PubMed

Morokuma, Junji; Durant, Fallon; Williams, Katherine B; Finkelstein, Joshua M; Blackiston, Douglas J; Clements, Twyman; Reed, David W; Roberts, Michael; Jain, Mahendra; Kimel, Kris; Trauger, Sunia A; Wolfe, Benjamin E; Levin, Michael

2017-04-01

Regeneration is regulated not only by chemical signals but also by physical processes, such as bioelectric gradients. How these may change in the absence of the normal gravitational and geomagnetic fields is largely unknown. Planarian flatworms were moved to the International Space Station for 5 weeks, immediately after removing their heads and tails. A control group in spring water remained on Earth. No manipulation of the planaria occurred while they were in orbit, and space-exposed worms were returned to our laboratory for analysis. One animal out of 15 regenerated into a double-headed phenotype-normally an extremely rare event. Remarkably, amputating this double-headed worm again, in plain water, resulted again in the double-headed phenotype. Moreover, even when tested 20 months after return to Earth, the space-exposed worms displayed significant quantitative differences in behavior and microbiome composition. These observations may have implications for human and animal space travelers, but could also elucidate how microgravity and hypomagnetic environments could be used to trigger desired morphological, neurological, physiological, and bacteriomic changes for various regenerative and bioengineering applications.

Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel

PubMed Central

Morokuma, Junji; Durant, Fallon; Williams, Katherine B.; Finkelstein, Joshua M.; Blackiston, Douglas J.; Clements, Twyman; Reed, David W.; Roberts, Michael; Jain, Mahendra; Kimel, Kris; Trauger, Sunia A.; Wolfe, Benjamin E.

2017-01-01

Abstract Regeneration is regulated not only by chemical signals but also by physical processes, such as bioelectric gradients. How these may change in the absence of the normal gravitational and geomagnetic fields is largely unknown. Planarian flatworms were moved to the International Space Station for 5 weeks, immediately after removing their heads and tails. A control group in spring water remained on Earth. No manipulation of the planaria occurred while they were in orbit, and space‐exposed worms were returned to our laboratory for analysis. One animal out of 15 regenerated into a double‐headed phenotype—normally an extremely rare event. Remarkably, amputating this double‐headed worm again, in plain water, resulted again in the double‐headed phenotype. Moreover, even when tested 20 months after return to Earth, the space‐exposed worms displayed significant quantitative differences in behavior and microbiome composition. These observations may have implications for human and animal space travelers, but could also elucidate how microgravity and hypomagnetic environments could be used to trigger desired morphological, neurological, physiological, and bacteriomic changes for various regenerative and bioengineering applications. PMID:28616247

Influence of the dark/light rhythm on the effects of UV radiation in the eyestalk of the crab Neohelice granulata.

PubMed

Vargas, Marcelo Alves; Geish, Marcio Alberto; Maciel, Fabio Everton; Cruz, Bruno Pinto; Filgueira, Daza de Moraes Vaz Batista; Ferreira, Gabrielle de Jesus; Nery, Luiz Eduardo Maia; Allodi, Silvana

2010-04-01

Crustaceans are interesting models to study the effects of ultraviolet (UV) radiation, and many species may be used as biomarkers for aquatic contamination of UV radiation reaching the surface of the Earth. Here, we investigated cell damage in the visual system of crabs Neohelice granulata that were acclimated to either 12L:12D, constant light, or constant dark, and were exposed to UVA or UVB at 12:00h (noon). The production of reactive oxygen species (ROS), antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO) damage, catalase activity, and pigment dispersion in the eye were evaluated. No significant differences from the three groups of controls (animals acclimated to 12L:12D, or in constant light, or not exposed to UV radiation) were observed in animals acclimated to 12L:12D, however, crabs acclimated to constant light and exposed to UV radiation for 30min showed a significant increase in ROS concentration, catalase activity, and LPO damage, but a decrease in ACAP compared with the controls. Crabs acclimated to constant darkness and exposed to UV for 30min showed a significantly increased ROS concentration and LPO damage, but the ACAP and catalase activity did not differ from the controls (animals kept in the dark while the experimental group was being exposed to UV radiation). Pigment dispersion in the pigment cells of eyes of animals acclimated to constant light was also observed. The results indicate that UVA and UVB alter specific oxidative parameters; however, the cell damage is more evident in animals deviated from the normal dark/light rhythm.

The role of the habenula-interpeduncular pathway in modulating levels of circulating adrenal hormones.

PubMed

Murray, M; Murphy, C A; Ross, L L; Haun, F

1994-01-01

The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282-3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2-3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic-adrenal medullary and adrenocortical pathways.

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards

PubMed Central

Burke, Kathryn A.; Franz, Theresa M.; Miller, Danielle N.; Schoenbaum, Geoffrey

2009-01-01

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald’s Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways1, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction2,3. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making4, was critical for the former but not for the latter form of conditioned reinforcement. PMID:18563088

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards.

PubMed

Burke, Kathryn A; Franz, Theresa M; Miller, Danielle N; Schoenbaum, Geoffrey

2008-07-17

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.

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

PubMed Central

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

2014-01-01

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

EFFECTS OF TOPICAL CORTICOSTEROID ADMINISTRATION ON INTRAOCULAR PRESSURE IN NORMAL AND GLAUCOMATOUS CATS

PubMed Central

Gosling, Allyson A; Kiland, Julie A; Rutkowski, Lauren E; Hoefs, Adam; Ellinwood, N Matthew; McLellan, Gillian J

2016-01-01

Objective to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG). Animals studied 5 normal and 11 FCG cats were studied in 2 cohorts. Procedures IOP was measured by a single, masked observer, once daily 3–5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; Balanced salt solution (BSS) applied to the contralateral eye, served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively. Results 8/11 FCG cats responded to topical CCS after 1–5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). 2/5 normal cats responded to topical CCS with appreciable but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg). Conclusions our data indicate that the incidence of steroid induced IOP elevation in cats is lower than previously published feline studies suggest. Cats with pre-existing compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats. PMID:26876736

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

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

Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com; Dezfoulian, Omid; Alirezaei, Masoud

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivomore » quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P < 0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P > 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.« less

Effects of a high protein diet on cognition and brain metabolism in cirrhotic rats.

PubMed

Méndez-López, M; Méndez, M; Arias, J; Arias, J L

2015-10-01

Hepatic encephalopathy (HE) is a neurological complication observed in patients with liver disease. Patients who suffer from HE present neuropsychiatric, neuromuscular and behavioral symptoms. Animal models proposed to study HE resulting from cirrhosis mimic the clinical characteristics of cirrhosis and portal hypertension, and require the administration of hepatotoxins such as thioacetamide (TAA). The aim of this study was to assess the effects of a high protein diet on motor function, anxiety and memory processes in a model of cirrhosis induced by TAA administration. In addition, we used cytochrome c-oxidase (COx) histochemistry to assess the metabolic activity of the limbic system regions. Male rats were distributed into groups: control, animals with cirrhosis, Control rats receiving a high protein diet, and animals with cirrhosis receiving a high protein diet. Results showed preserved motor function and normal anxiety levels in all the groups. The animals with cirrhosis showed an impairment in active avoidance behavior and spatial memory, regardless of the diet they received. However, the animals with cirrhosis and a high protein diet showed longer escape latencies on the spatial memory task. The model of cirrhosis presented an under-activation of the dentate gyrus and CA3 hippocampal subfields and the medial part of the medial mammillary nucleus. The results suggest that a high protein intake worsens spatial memory deficits shown by the TAA-induced model of cirrhosis. However, high protein ingestion has no influence on the COx hypoactivity associated with the model. Copyright © 2015 Elsevier Inc. All rights reserved.

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

PubMed

Watters, Jennifer M; Brundage, Susan I; Todd, S Rob; Zautke, Nathan A; Stefater, J A; Lam, J C; Muller, Patrick J; Malinoski, Darren; Schreiber, Martin A

2004-09-01

Lactated Ringer's (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-alpha) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-alpha gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus.

PubMed

Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

2012-03-01

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

Alleviation of cyclophosphamide-induced immunosuppression in Wistar rats by onion lectin (Allium cepa agglutinin).

PubMed

Kumar, Vaddi P; Venkatesh, Yeldur P

2016-06-20

In various traditional medicines, onion has been classified as an immune-boosting food. Recent studies have claimed this property due to the presence of bioactive organosulfur compounds, prebiotic fructo-oligosaccharides and an immunomodulatory protein, lectin (Allium cepa agglutinin; ACA) (Prasanna and Venkatesh, 2015. Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro. Int. Immunopharmacol. vol. 26, pp. 304-313). The aim of this study was to evaluate the immunoprotective properties of ACA in normal and cyclophosphamide (CP; 100μg/kg)-induced immunosuppressed Wistar rats. Wistar rats were administrated different doses of ACA (1, 10, and 100μg) to respective groups in normal as well as immunosuppressed animals. The effect of ACA on the status of immune organs was assessed by examining the splenic and thymic indices, and histopathological changes. The biomarkers for humoral immunity (serum IgG and IgA levels) and serum pro-inflammatory markers (COX-2, TNF-α and IL-10) were measured by ELISA. ACA showed immunoprotective properties by significantly promoting the restoration of lymphoid cell count by ~6 fold vs. model control (immunosuppressed animals) and promotes the immune response significantly (~1.5-fold) in CP-induced immunosuppressed animals compared to model control; production of pro-inflammatory molecules (COX-2 and nitric oxide) and expression levels of immune regulatory molecule (TNF-α) were elevated in a dose-dependent manner. The observed in vivo results suggest that ACA has the potential to be used as a nutritional therapeutic to boost the immune status of immunosuppressed subjects brought about by CP administration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Effect of chronic intake of dietary fiber complex on the intestinal structure and function in hypercholesterolemic rats].

PubMed

Ma, Zhengwei; Zhang, Xizhong

2003-07-01

To investigate the long-term effect of dietary fiber complex (DFC) on intestinal structure and function in hypercholesterolemic rats, 60 healthy SD rats were feed with food rich in lipids and hypercholesterolemic animal models were established. The animals were randomly divided into 5 groups. Rats were fed DFC at levels of 4%, 16%, or 64% for three month in the experimental groups. Wheat fiber was used in the hypercholesterolemic control (HC) group and rats feeding on normal food were used as normal control (NC). Morphology of the small intestine, reticum and caecum were observed by light and electron microscope examination. Intestinal function was measured physically. The results showed that (1) compared with NC group, fecal weight was significantly raised in DFC group of higher level (group D and E, P < 0.05); (2) the weights of small intestine wall in D and E group were significantly higher than those of NC and HC group and weights of caecum wall in E group were significantly higher than those of NC and HC group (P < 0.05); (3) widen villi and thickened muscle layer of small intestine were observed in DFC group of higher level. No demonstrable changes in reticulum morphology in any group of animals were found under the observation of light microscope (4) microvilla becoming short and/or absent, mitochondria swelling, impairment of the integrity of the cristae were commonly observed in DFC groups. Conclusions Long-term intake of DFC composed mainly of Hippophae rhamnoides L, Bran, oat bran and guar gum at higher levels might induce some morphological changes of intestine and caecum. Therefore, DFC might be used at low level as an effective cholesterol-lowering agent.

The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural Damage in Rat Offspring's Hippocampus.

PubMed

Sadeghi, Akram; Ebrahimzadeh Bideskan, Alireza; Alipour, Fatemeh; Fazel, Alireza; Haghir, Hossein

2013-02-01

The aim of this study was to investigate ascorbic acid and garlic protective effects on lead-induced neurotoxicity during rat hippocampus development. 90 pregnant wistar rats were divided randomly into nine groups: 1- Animals received leaded water (L). 2- Rats received leaded water and ascorbic acid (L+AA). 3- Animals received leaded water and garlic juice (L+G). 4-Animals received leaded water, ascorbic acid and garlic juice (L+G+AA). 5- Rats treated with ascorbic acid (AA). 6- Rats treated with garlic juice (G). 7- Rats treated with ascorbic acid and garlic juice (AA+G). 8- Rats treated with tap water plus 0.4 ml/l normal hydrogen chloride (HCl) and 0.5 mg/l Glucose (Sham). 9- Normal group (N). Leaded water (1500 ppm), garlic juice (1 ml/100g/day, gavage) and ascorbic acid (500 mg/kg/day, IP) were used. Finally, blood lead levels (BLL) were measured in both rats and their offspring. The rat offspring brain sections were stained using Toluidine Blue and photographed. Dark neurons (DNs) were counted to compare all groups. BLL significantly increased in L group compared to control and sham groups and decreased in L+G and L+AA groups in comparison to the L group (P<0.05). the number of DNs in the CA1, CA3, and DG of rat offspring hippocampus significantly increased in L group in comparison to control and sham groups (P<0.05) and decreased in L+G and L+AA groups compared to L group (P<0.05). Garlic juice and ascorbic acid administration during pregnancy and lactation may protect lead-induced neural damage in rat offspring hippocampus.

Bright light induces choroidal thickening in chickens.

PubMed

Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

2013-11-01

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

The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

PubMed Central

Dickins, Ross A.; Frew, Ian J.; House, Colin M.; O'Bryan, Moira K.; Holloway, Andrew J.; Haviv, Izhak; Traficante, Nadia; de Kretser, David M.; Bowtell, David D. L.

2002-01-01

The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including β-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division. PMID:11884614

[Intensity of DNA synthesis in animal organs after a flight on the Kosmos-782 biosatellite].

PubMed

Guseĭnov, F T; Egorov, I A; Komolova, G S; Tigranian, R A

1979-01-01

With respect to H3-thymidine incorporation the rate of DNA synthesis in the liver, spleen and thymus of rats was determined in flight and synchronous rats. Six hours post-flight the rate of H3-thymidine incorporation into the liver of flight rats did not differ from the normal (vivarium controls) and was 50% higher than in the synchronous rats. In the spleen and thymus of flight animals this parameter was 60 and 33% below the norm. Similar but less pronounced changes in the spleen were found in the synchronous rats. Twenty-five days postflight the rate of DNA synthesis in lymph organs recovered completely and tended to increase, whereas in the liver it remained significantly below the norm.

EFFECTS OF IN VITRO RADIOCOBALT IRRADIATION OF RABBIT OVA ON SUBSEQUENT DEVELOPMENT IN VIVO WITH SPECIAL REFERENCE TO THE IRRADIATION OF MATERNAL ORGANISM

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

Chang, M.C.; Hunt, D.M.

Fertilized rabbit ova recovered one to six days after mating were irradiated in vitro from a radiocobalt source and then transplanted into recipient animals. When examined 22 to 28 days later 44, 33, 8 and 0% of ova irradiated respectively at 50, 100, 1,000 and 5,000 r developed into apparently normal fetuses without external or internal malformation. No significant differential sensitivity was apparent in ova irradiated at different ages. It was found further that 34, 36, 19 and 10% of two-, 4-, and 6-day ova irradiated respectively in vitro at 200, 400, 600, and 800 r developed into "normal" fetuses.more » Again no malformation of fetuses and no differential radiosensitivity between ova of different ages were observed. Following whole body irradiation at 400 r, it was found that 40% of non-irradiated ova developed into normal fetuses when transplanted into recipient animals that had been irradiated (vs. 36% in the irradiation of ova alone). However, only 17% of estimated ova developed into "normal" fetuses when pregnant rabbits were irradiated 2, 4 or 6 days after insemination (vs. 64% in the control). It appears that irradiation of the maternal organism influences embryonic development and that irradiation of pregnant animals exerts a combination of ill effects, on the ova and on their environment. Cytological study of irradiated blastocysts revealed no chromosomal breakage immediately after irradiation. Chromosomal abnormalities, fragmentation and condensation of chromatin were observed during the culture of irradiated blastocysts in accordance with the dosages applied. From this study it is concluded that (1) although 50 r may affect embryonic development, there seems to be no differential effect up to 400 r, above which greater prenatal death occurs; (2) before implantation, irradiated ova either die or develop into apparently normal fetuses and there is no evidence of differential radiosensitivity at various stages of development; (3) irradiation of the maternal organism alone also affects embryonic development; and (4) radiation damage affects a fundamental biological system which leads to the nuclear damage and failure of mitosis, and the death of ova. (auth)« less

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

PubMed

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

1990-01-01

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

Introducing a novel mechanism to control heart rate in the ancestral Pacific hagfish.

PubMed

Wilson, Christopher M; Roa, Jinae N; Cox, Georgina K; Tresguerres, Martin; Farrell, Anthony P

2016-10-15

Although neural modulation of heart rate is well established among chordate animals, the Pacific hagfish (Eptatretus stoutii) lacks any cardiac innervation, yet it can increase its heart rate from the steady, depressed heart rate seen in prolonged anoxia to almost double its normal normoxic heart rate, an almost fourfold overall change during the 1-h recovery from anoxia. The present study sought mechanistic explanations for these regulatory changes in heart rate. We provide evidence for a bicarbonate-activated, soluble adenylyl cyclase (sAC)-dependent mechanism to control heart rate, a mechanism never previously implicated in chordate cardiac control. © 2016. Published by The Company of Biologists Ltd.

Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model.

PubMed

Tanen, David A; Danish, David C; Clark, Richard F

2003-03-01

Crotalidae Polyvalent Immune Fab (CroFab; FabAV) antivenom prevents a decrease in perfusion pressures in intramuscular crotaline envenomation compared with normal saline solution. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized and instrumented swine were injected intramuscularly with 6 mg/kg Crotalus atrox venom into the anterior tibialis muscle of each hind limb (time 0). One hour after envenomation (time 1 hour), animals were randomized to receive 8 vials of reconstituted FabAV or an equal volume of normal saline solution (control) through a central venous line. The main outcome variable was the area under the perfusion-time curve (AUC) of the anterior compartment of the hind limb measured from time 1 hour to time 8 hours. Perfusion pressure was defined as mean arterial pressure-compartment pressure. Additionally, physiologic variables, including pulse rate, prothrombin time, fibrinogen level, platelet count, hemoglobin level, and hematocrit level, were monitored. Venom injection resulted in a decrease in average perfusion pressures from 54.1 mm Hg (time 0) to 31.7 mm Hg (time 1 hour). Comparison of AUC between groups from time 1 hour (time of treatment) to the completion of the study at time 8 hours revealed a 57% greater AUC in animals that received FabAV (mean+/-SD: 211.1+/-67.9 versus 134.5+/-55.8 mm Hg/h; P =.036; 95% confidence interval for difference 5.9 to 147.3). Comparison of the time curves for the mean prothrombin time from time 1 hour to the completion of the study by means of repeated-measures analysis of variance revealed a significant increase in the control group (P =.02). No significant difference was detected in the time curves for the means of mean arterial pressure, compartment pressure, pulse rate, hemoglobin level, hematocrit level, fibrinogen level, or platelet count over the course of the study. FabAV was found to significantly increase survival time when compared with the effect of the normal saline solution control from time 1 hour to time 8 hours, as determined by means of Kaplan-Meier estimation and the log-rank test (P =.029). FabAV limits the decrease in perfusion pressures in the anterior leg compartment after intramuscular crotaline venom injection in swine compared with saline solution. In addition, FabAV might prevent the development of coagulopathy and increase survival time in this model.

Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

PubMed Central

Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

2013-01-01

Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P < 0.05), whereas levels in animals with cardiac failure were intermediate. Conversely, TGFβ2 and TGFβ3 gene expression in lungs were higher in healthy animals than in ascitic animals in both groups (P < 0.05). TGFβ1, TβRI, and TβRII mRNA gene expression among healthy, ascitic, and chickens with cardiac failure showed no differences (P > 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

Effect of sleep-wake reversal and sleep deprivation on the circadian rhythm of oxygen toxicity seizure susceptibility.

NASA Technical Reports Server (NTRS)

Dexter, J. D.; Hof, D. G.; Mengel, C. E.

1972-01-01

Albino Sprague-Dawley rats were exposed in a previously O2 flushed, CO2 free chamber. The exposure began with attainment of 60 psi (gauge) and the end point was the first generalized oxygen toxicity seizure. Animals were exposed to reversal diurnal conditions since weanlings until their sleep-wake cycles had completely reversed, and then divided into four groups of 20 based on the time of day exposed. The time of exposure to oxygen at high pressure prior to seizure was now significantly longer in the group exposed from 1900 to 2000 hr and a reversal of the circadian rhythm of oxygen toxicity seizure susceptibility was noted. Animals maintained on normal diurnal conditions were deprived of sleep on the day of exposure for the 12 hours prior to exposure at 1900 hr, while controls were allowed to sleep. There was no significant differences in the time prior to seizure between the deprived animals and the controls with an n = 40. Thus the inherent threshold in susceptibility to high-pressure oxygen seizures seems not to be a function of sleep itself, but of some biochemical/physiologic event which manifests a circadian rhythm.

Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice.

PubMed

Ojewole, J A O; Adewunmi, C O

2003-01-01

Diabetes mellitus is a debilitating hormonal disorder in which strict glycemic control and prevention of associated complications are of crucial importance. This study was designed to evaluate the hypoglycemic effect of methanolic extract of mature, green fruits of Musa paradisiaca (MEMP) in normal (normoglycemic) and streptozotocin (STZ)-treated, diabetic (hyperglycemic) mice, using chlorpropamide as the reference antidiabetic agent. MEMP (100-800 mg/kg p.o.) induced significant, dose-related (p < 0.05-0.001) reductions in the blood glucose concentrations of both normal and diabetic mice. Chlorpropamide (250 mg/kg p.o.) also produced significant (p < 0.01-0.001) reductions in the blood glucose concentrations of normal and diabetic mice. The results of this experimental study indicate that, in the mammalian model used, MEMP possesses hypoglycemic activity. Although the precise mechanism of the hypoglycemic action of MEMP is still unclear and will have to await further studies, it could be due, at least in part, to stimulation of insulin production and subsequent glucose utilization. Nevertheless, the findings of this experimental animal study indicate that MEMP possesses hypoglycemic activity, and thus lends credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetic mellitus among the Yoruba-speaking people of South-Western Nigeria.

The cell biology of aging.

PubMed

Hayflick, L

1979-07-01

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

Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.

PubMed

Aagaard, Niels Kristian; Grøfte, Thorbjørn; Greisen, Jacob; Malmlöf, Kjell; Johansen, Peter B; Grønbaek, Henning; Ørskov, Hans; Tygstrup, Niels; Vilstrup, Hendrik

2009-10-01

Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism. Five groups of rats were included: (1) free-fed controls (2) pair-fed controls (3) prednisolone (delcortol, 4 mg x kg(-1) x day(-1)) (4) prednisolone and GH (1 mg x kg(-1) x day(-1)) (5) prednisolone and Ipamorelin (0.5 mg x kg(-1) x day(-1)). After seven days the hepatic capacity of urea-N synthesis (CUNS) was determined in parallel with measurements of liver mRNA levels of urea cycle enzymes, whole-body N-balance, and N-contents of various organs. Compared to pair-fed controls, prednisolone increased CUNS (p<0.01) as well as the expression of urea cycle genes (p<0.01), and decreased N-balance (p<0.01) as well as organ N-contents (p<0.05). Compared to prednisolone treated animals, co-administration of GH reduced CUNS by 33% (p<0.01), normalized urea cycle gene expression, improved N-balance 2.5-fold, and normalized or improved organ N-contents. In prednisolone treated rats Ipamorelin reduced CUNS by 20% (p<0.05), decreased the expression of urea cycle enzymes, neutralised N-balance, and normalized or improved organ N-contents. Accelerated nitrogen wasting in the liver and other organs caused by prednisolone treatment was counteracted by treatment with either GH or its secretagogue Ipamorelin, though at the doses given less efficiently by the latter. This functional study of animals confirms that the GH secretagogue exerts GH related metabolic effects and may be useful in the treatment of steroid-induced catabolism.

Effects of xylitol on blood glucose, glucose tolerance, serum insulin and lipid profile in a type 2 diabetes model of rats.

PubMed

Islam, Md Shahidul; Indrajit, Mitesh

2012-01-01

The present study was conducted to examine the antidiabetic effects of xylitol in a type 2 diabetes rat model. Six-week-old male Sprague-Dawley rats were randomly divided into 3 groups: normal control (NC), diabetic control (DBC) and xylitol (XYL). Diabetes was induced only in the DBC and XYL animal groups by feeding them a 10% fructose solution for 2 weeks followed by an injection (i.p.) of streptozotocin (40 mg/kg body weight). One week after the streptozotocin injection, the animals with a nonfasting blood glucose level of >300 mg/dl were considered to be diabetic. The XYL group was fed further with a 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 5 weeks of intervention, food and fluid intake, body weight, blood glucose, serum fructosamine and most of the serum lipids were significantly decreased, and serum insulin concentration and glucose tolerance ability was significantly increased in the XYL group compared to the DBC group. Liver weight, liver glycogen and serum triglycerides were not influenced by feeding with xylitol. The data of this study suggest that xylitol can be used not only as a sugar substitute but also as a supplement to antidiabetic food and other food products. Copyright © 2012 S. Karger AG, Basel.

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

NASA Astrophysics Data System (ADS)

Beier, Marion

1999-09-01

Inner ear stones (otoliths) of developing cichlid fish ( Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a long-term (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.

Hormonal, biochemical, and hematological profiles in female camels (Camelus dromedarius) affected with reproductive disorders.

PubMed

Ali, A; Tharwat, M; Al-Sobayil, F A

2010-04-01

The aim of this study was to assess the blood profiles in female camels affected with common reproductive disorders. Estradiol-17beta (E(2)), progesterone (P(4)), thyroxin (T(4)), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), magnesium (Mg), cholesterol, glucose, triglycerides, total protein, albumin, globulin, hematocrite, and total and differential white blood cell counts (WBC) were determined in blood of female camels affected with endometritis (n=15), vaginal adhesions (n=15), and ovarian cysts (n=15). Normal cyclic animals were used as controls (n=15). Diagnosis of reproductive disorders was based on transrectal palpation, ultrasonographic examination, and exploration of the vagina. Increased WBC counts (P=0.03) and a tendency for neutrophelia (P=0.05) were noted in female camels with vaginal adhesions. These animals were also characterized by having higher concentration of serum P(4) (P=0.0001), T(4) (P=0.001) and total protein (P=0.007), in comparison with female camels with endometritis, ovarian cysts, or controls. Animals having ovarian cysts with thin walls and homogenous hypoechogenic contents had greater serum E(2) (P=0.001) and P(4) (P=0.0001) than those having ovarian cysts with thick walls and non-homogenous echogenic contents. Animals with endometritis, vaginal adhesions, and ovarian cysts revealed lower serum Zn concentration than that of control group (P=0.003). Other blood parameters did not differ significantly compared to controls. In conclusion, this is the first report characterizing blood constituents in female camels with various reproductive disorders. These profiles may be valuable in clarifying the etio-pathogenesis of these disorders. Copyright 2009 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Development of the Gecko (Pachydactylus turneri) Animal Model during Foton M-2 to Study Comparative Effects of Microgravity in Terrestrial and Aquatic Organisms

NASA Technical Reports Server (NTRS)

Almeida, E. A.; Roden, C.; Phillips, J. A.; Globus, R. K.; Searby, N.; Vercoutere, W.; Morey-Holton, E.; Gulimova, V.; Saveliev, S.; Tairbekov, M.;

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

PubMed

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

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

[Determination of micro and macronutrients in the cattle of the Venezuelan plains and their influence on the origin of bovine paraplegic syndrome].

PubMed

Rojas, H; Serrano, J R; DiPolo, R

1994-01-01

We report a study carried out in three livestock-producing regions of Venezuela to determine the mineral status of grazing cattle and its relationship to the Síndrome Parpléjico del Bovino (SPB). Animal tissue samples from blood and liver were collected from a total of 17 farms within three regions: southwest (Apure), central (Guárico) and southeast (Bolívar) both during the dry and rainy seasons. In SPB free animals, the serum levels of sodium, potassium, chloride, magnesium, total and ionized calcium, phosphorus, and creatinine, were within the normal range. Glucose was found to be deficient in cattle from Bolívar and Guárico states and normal in Apure. With the exception of liver copper and serum zinc, all the other microelements analyzed (liver cobalt, and molybdenum, and serum iron) were found to be normal. Copper was found to be low in all regions studied with a mean value of 74.8 ppm indicating a moderate deficiency of this element. Similarly, in the central and southwest regions, zinc was found to be close to 0.34 ppm, significantly lower than the critical level of 0.7 ppm. In order to determine the effect of the dry and rainy seasons on the content of macro and microelements, controlled group of cattle from the three regions were followed in their contents of magnesium, calcium, copper and iron. In the dry season all of these elements tended to be much lower, showing a significant increase in the rainy season. This increase was much greater in cattle that received mineral supplementation and sanitary treatment. Bovines with diagnosis of SPB showed: low liver copper content, low serum magnesium and phosphorus levels significantly higher that control cattle.

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

PubMed

Tutton, P J; Barkla, D H

1976-08-11

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

Therapeutic effect of adeno-associated virus (AAV)-mediated ADNF-9 expression on cochlea of kanamycin-deafened guinea pigs.

PubMed

Zheng, Guoxi; Zhu, Zhu; Zhu, Kang; Wei, Junrong; Jing, Yang; Duan, Maoli

2013-10-01

rAAV-NT4-ADNF-9 could ameliorate the damage to auditory function and repair previous impairment of cochlear hair cell loss induced by kanamycin. To investigate the therapeutic effect of ADNF-9 on cochlear hair cells using the recombinant adeno-associated virus (AAV) carrying fusion gene NT4-ADNF-9 and the kanamycin-deafened guinea pig model. Forty white guinea pigs with normal auricle reflex and normal auditory brainstem responses (ABRs) were randomly divided into four groups. Kanamycin was administered to the animals in groups A, B, and C to establish the deafened guinea pig model. rAAV-NT4-ADNF-9, vector only, and artificial perilymph were then delivered to the cochlear tissue of animals in groups A, B, and C, respectively, through the round window membrane. Animals in group D did not receive any treatment and acted as normal controls. The hearing thresholds on the surgery side were recorded before and after the transfection treatment. Fourteen days after treatment, cochleae were removed for paraffin slide preparation and cochlear surface preparation. A phase contrast microscope was used to observe the protective effect of ADNF-9 on hair cells. Significant reduction of the ABR threshold was observed after rAAV-NT4-ADNF-9 treatment (p < 0.05). After 14 days of treatment, the ABR threshold was also significantly different between the rAAV-NT4-ADNF-9-infected group and the non-infected group. Moreover, phase contrast microscopy showed significantly less hair cell damage or hair cell loss in the group treated with rAAV-NT4-ADNF-9 than in the groups treated with vector only or artificial perilymph (p < 0.05).

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

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

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

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

Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

NASA Technical Reports Server (NTRS)

Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

1996-01-01

It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

[General characteristics of an experiment to study the ontogeny of rats on board the Kosmos-1514 biosatellite].

PubMed

Serova, L V; Denisova, L A; Apanasenko, Z I; Briantseva, L A; Chel'naia, N A

1985-01-01

Ten female Wistar rats were exposed to zero-g during 5 days, i. e., from gestation day 13 to day 18. After recovery the flight animals showed a significant delay in weight gain, thymus involution, decreased liver weight, hemoglobin concentration. Nevertheless, their reproductive function did not differ from that of the controls: the rate of preimplantation and total fetal mortality as well as the number of live fetuses were very similar in the experimental and control animals. The flight group showed a slight decline of fetal weight and water content. The size of the litters produced by the flight and control rats was identical but the mortality rate of those former during the first 7 days after birth was significantly higher. This experiment has demonstrated that the mammalian fetus exposed to zero-g during the last term of pregnancy, i. e., at the stage of active organogenesis, can grow and develop in the normal way. A large body of biological material has been obtained for biochemical and histological examinations that will help evaluate the condition of dams, fetuses, and newborns.

Extracorporeal gas exchange with the DeltaStream rotary blood pump in experimental lung injury.

PubMed

Dembinski, Rolf; Kopp, Rüdger; Henzler, Dietrich; Hochhausen, Nadine; Oslender, Nicole; Max, Martin; Rossaint, Rolf; Kuhlen, Ralf

2003-06-01

In most severe cases of the acute respiratory distress syndrome, veno-venous extracorporeal membrane oxygenation (ECMO) can be used to facilitate gas exchange. However, the clinical use is limited due to the size and the concomitant risk of severe adverse events of conventionally-used centrifugal blood pumps with high extracorporeal blood volumes. The DeltaStream blood pump is a small-sized rotary blood pump that may reduce extracorporeal blood volume, foreign surfaces, contact activation of the coagulation system, and blood trauma. The aim of the present study was to test the safety and efficacy of the DeltaStream pump for ECMO in animals with normal lung function and experimental acute lung injury (ALI). Therefore, veno-venous ECMO was performed for 6 hours in mechanically ventilated pigs with normal lung function (n=6) and with ALI induced by repeated lung lavage (n=6) with a blood flow of 30% of the cardiac output. Gas flow with a FiO2 of 1.0 was set to equal blood flow. With a mean activated clotting time of 121 +/- 22 s, no circulatory impairment or thrombus formation was revealed during ECMO. Furthermore, free plasma Hb did not increase. In controls, hemodynamics and gas exchange remained unchanged. In animals with ALI, hemodynamics remained stable and gas transfer across the extracorporeal oxygenators was optimal, but only in 2 animals was a marked increase in PaO2 observed. CO2 removal was efficacious in all animals. We concluded that the DeltaStream blood pump may be used for veno-venous ECMO without major blood damage or hemodynamic impairment.

Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

PubMed

McCall, M A; Tieman, D G; Hirsch, H V

1982-11-04

In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

Motor neuronal activity varies least among individuals when it matters most for behavior

PubMed Central

Cullins, Miranda J.; Shaw, Kendrick M.; Gill, Jeffrey P.

2014-01-01

How does motor neuronal variability affect behavior? To explore this question, we quantified activity of multiple individual identified motor neurons mediating biting and swallowing in intact, behaving Aplysia californica by recording from the protractor muscle and the three nerves containing the majority of motor neurons controlling the feeding musculature. We measured multiple motor components: duration of the activity of identified motor neurons as well as their relative timing. At the same time, we measured behavioral efficacy: amplitude of grasping movement during biting and amplitude of net inward food movement during swallowing. We observed that the total duration of the behaviors varied: Within animals, biting duration shortened from the first to the second and third bites; between animals, biting and swallowing durations varied. To study other sources of variation, motor components were divided by behavior duration (i.e., normalized). Even after normalization, distributions of motor component durations could distinguish animals as unique individuals. However, the degree to which a motor component varied among individuals depended on the role of that motor component in a behavior. Motor neuronal activity that was essential for the expression of biting or swallowing was similar among animals, whereas motor neuronal activity that was not essential for that behavior varied more from individual to individual. These results suggest that motor neuronal activity that matters most for the expression of a particular behavior may vary least from individual to individual. Shaping individual variability to ensure behavioral efficacy may be a general principle for the operation of motor systems. PMID:25411463

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Anesthetic Neuroprotection in Experimental Stroke in Rodents: A Systematic Review and Meta-analysis.

PubMed

Archer, David P; Walker, Andrew M; McCann, Sarah K; Moser, Joanna J; Appireddy, Ramana M

2017-04-01

Patients undergoing endovascular therapy for acute ischemic stroke may require general anesthesia to undergo the procedure. At present, there is little clinical evidence to guide the choice of anesthetic in this acute setting. The clinical implications of experimental studies demonstrating anesthetic neuroprotection are poorly understood. Here, the authors evaluated the impact of anesthetic treatment on neurologic outcome in experimental stroke. Controlled studies of anesthetics in stroke using the filament occlusion model were identified in electronic databases up to December 15, 2015. The primary outcome measures, infarct volume, and neurologic deficit score were used to calculate the normalized mean difference for each comparison. Meta-analysis of normalized mean difference values provided estimates of neuroprotection and contributions of predefined factors: study quality, the timing of treatment, and the duration of ischemia. In 80 retrieved publications anesthetic treatment reduced neurologic injury by 28% (95% CI, 24 to 32%; P < 0.0001). Internal validity was high: publication bias enhanced the effect size by 4% or less, effect size increased with study quality (P = 0.0004), and approximately 70% of studies were adequately powered. Apart from study quality, no predefined factor influenced neuroprotection. Neuroprotection failed in animals with comorbidities. Neuroprotection by anesthetics was associated with prosurvival mechanisms. Anesthetic neuroprotection is a robust finding in studies using the filament occlusion model of ischemic stroke and should be assumed to influence outcomes in studies using this model. Neuroprotection failed in female animals and animals with comorbidities, suggesting that the results in young male animals may not reflect human stroke.

Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase.

PubMed Central

Baker, G L; Corry, R J; Autor, A P

1985-01-01

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3840348

A putative role for hypothalamic glucocorticoid receptors in hypertension induced by prenatal undernutrition in the rat.

PubMed

Pérez, Hernán; Soto-Moyano, Rubén; Ruiz, Samuel; Hernández, Alejandro; Sierralta, Walter; Olivares, Ricardo; Núñez, Héctor; Flores, Osvaldo; Morgan, Carlos; Valladares, Luis; Gatica, Arnaldo; Flores, Francisco J

2010-10-08

Prenatal undernutrition induces hypertension later in life, possibly by disturbing the hypothalamo-pituitary-adrenal axis through programming decreased expression of hypothalamic glucocorticoid receptors. We examined the systolic blood pressure, heart rate and plasma corticosterone response to intra-paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily (40% of diet consumed by well-nourished controls). At day 40 of postnatal life (i) intra-paraventricular administration of dexamethasone significantly reduced at least for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the plasma corticosterone (-40.0%) in normal animals, while producing lower effects (-5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra-paraventricular administration of the antiglucocorticoid receptor ligand mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0% increase, respectively) to those induced by dexamethasone, being these not significant in undernourished animals; (iii) intra-paraventricular corticosterone did not exert any significant effect. Results suggest that the low sensitivity of paraventricular neurons to glucocorticoid receptor ligands observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor expression, found in the hypothalamus of undernourished animals. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

PubMed

Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

2014-08-01

Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effect of Anterior Stromal Puncture Using Q-Switched Nd:YAG Laser on Corneal Wound Healing

PubMed Central

Hamdy Abdelaziz, Mohamed; Fouad Ghoneim, Dina; Abdelkawi Ahmed, Salwa; Taher, Ibraheim Mohyeldin; Abdel- Salam, Ahmed Medhat

2014-01-01

Introduction: Recurrent corneal erosion occurs when the wounded corneal epithelium failed to adhere to the underlying stroma. Therefore, this work aimed to assess the effect of treatment of corneal injury using Q- switched Nd:YAG laser. Method: Twenty one New Zealand male rabbits weighing 2-2.5 kg and 3 months old were classified into three main groups. The control group: did not received any treatment (n=3 rabbits). The rest of the animals (n= 18 rabbits), corneal epithelium was injured by syringe needle and blade 15 and divided into:(A) Normal healing group: which was divided into three subgroups (n=3 rabbits each), and the animals were left for normal healing for1 day, 1 week, and 4 weeks respectively, (B) Laser treated group: divided into three subgroups (n=3 rabbit seach) and subjected to anterior stromal puncture using Q-switched Nd: YAG laser on corneal sub-epithelium or superficial stroma, and the animals were left for 1 day, 1 week, and 4 weeksrespectively. After the demonstrated periods, the corneas were isolated for estimation of total protein content, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), total antioxidative capacity (TAC), total oxidative capacity (TOC) and oxidative stress index (OSI). Results: The present results of corneal total protein showed increment in the percentage change in normal healed groups after 1 day, 1 week and 4 weeks by values of 93%, 68% and 39%. In Q-switched Nd: YAG laser treated group the results showed better improvement in corneal protein than normal healed group with percentage changes of 58%, 29%, and 7.5% respectively. In SDS- PAGE, a protein band at 110 KD appeared in the migrating epithelium for both normal healed group and Q-switched Nd:YAG laser treated group with changes in the peaks intensities at middle and low molecular weight regions. Moreover, after 4 weeks the peak at 110 KD disappeared in the wounded epithelium treated with Q-switched Nd:YAG. After four weeks, the OSI in laser treated corneas showed pronounced balance between antioxidative capacityand oxidative capacity. Conclusion: Anterior stromal puncture by Q-switched Nd:YAG laser is an effective, simple, safe and promising procedure to treat recurrent corneal erosion than normal healing. PMID:25653810

Endoscopic colostomy with percutaneous colopexy: an animal feasibility study.

PubMed

Bustamante-Lopez, Leonardo Alfonso; Sulbaran, Marianny; Nahas, Sergio Carlos; de Moura, Eduardo Guimaraes Horneaux; Nahas, Caio Sergio; Marques, Carlos Frederico; Sakai, Christiano; Cecconello, Ivan; Sakai, Paulo

2017-04-01

Indications for colostomy in colorectal diseases are obstruction of the large bowel, such as in cancer, diverticular disease in the acute phase, post-radiotherapy enteritis, complex perirectal fistulas, anorectal trauma and severe anal incontinence. Some critically ill patients cannot tolerate an exploratory laparotomy, and laparoscopic assisted colostomy also requires general anesthesia. To evaluate the feasibility, safety and efficacy of performing colostomy assisted by colonoscopy and percutaneous colopexy. Five pigs underwent endoscopic assisted colostomy with percutaneous colopexy. Animals were evaluated in post-operative days 1, 2, 5 and 7 for feeding acceptance and colostomy characteristics. On day 7 full colonoscopy was performed on animals followed by exploratory laparotomy. Average procedure time was 27 minutes (21-54 min). Postoperative mobility and feeding of animals were immediate after anesthesia recovery. Position of the colostomy, edges color, appearance of periostomal area, as well as its function was satisfactory in four animals. Retraction of colostomy was present in one pig. The colonoscopy and laparotomy control on the seventh day were considered as normal. A bladder perforation that was successfully repaired through the colostomy incision occurred in one pig. The main limitation of this study is its experimental nature. Endoscopic assisted colostomy with percutaneous colopexy proves to be a safe and effective method with low morbidity for performing colostomy in experimental animals, with possible clinical application in humans.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture.

PubMed

Guimarães, Ana Paula Franttini Garcia Moreno; Butezloff, Mariana Maloste; Zamarioli, Ariane; Issa, João Paulo Mardegan; Volpon, José Batista

2017-11-01

To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.

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

PubMed

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

2017-01-01

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

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

PubMed Central

Verhaegen, Frank; De Ruysscher, Dirk

2017-01-01

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

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

PubMed Central

Wicks, Deidre

2011-01-01

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

Effects of sympathetic stimulation on cerebral and ocular blood flow. Modification by hypertension, hypercapnia, acetazolamide, PGI2 and papaverine.

PubMed

Beausang-Linder, M

1982-02-01

The effect of unilateral, electrical stimulation of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI2 was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI2. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12% blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI2-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.

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

PubMed

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

2010-02-15

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

Correlation of cytotoxic activity in lungs to recovery of normal and gamma-irradiated cotton rats from respiratory syncytial virus infection

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

Sun, C.S.; Wyde, P.R.; Knight, V.

1983-10-01

Cotton rats (Sigmodon hispidus) that were exposed to 300, 600, or 900 rads of gamma irradiation and inoculated intranasally 2 days later with respiratory syncytial virus (RSV) exhibited prolonged virus shedding and delayed humoral and cytotoxic immune responses compared with comparably inoculated nonirradiated control rats. In nonirradiated animals and in animals exposed to 300 and 600 rads, levels of virus declined and then disappeared from the lungs during the period in which cytotoxic activity was maximal in the lungs of these animals. In contrast, in the group of cotton rats exposed to 900 rads of irradiation, local cytotoxic activity remainedmore » low throughout the 11-day observation period, and virus was not eliminated from the lungs. Although virus-neutralizing antibodies in serum and lavage fluids from these animals may have been involved, correlation of antibody concentrations with virus clearance from lungs was not as evident. These data suggest that cytotoxic effector cells have a positive role in eliminating RSV from the lungs of unprimed cotton rats.« less

Does dietary hyperphagia contradict the lipostatic theory?

PubMed

Ramirez, I

1990-01-01

It has frequently been suggested that body weight or fat somehow exerts an inhibitory influence on food intake in a way that acts to maintain a stable body weight or fat. The principal evidence supporting this idea is that animals that have been induced to overeat and become overweight by various means, eat less than control rats when they are permitted to eat freely. If the degree of suppression of appetite by overweight is as large as several experiments suggest, then dietary hyperphagia should be self-limiting. Any overeating induced by dietary treatments should disappear after animals become moderately overweight. Animals fed some kinds of hyperhagia-promoting diets do show this pattern. However, animals fed other kinds of diets do not show this pattern, and with most diets, dietary hyperphagia continues for extended periods. This implies that either 1) overweight does not suppress appetite as much as suggested by various authorities, 2) dietary manipulations can override normal regulatory mechanisms, or 3) certain diets induce irreversible changes in body fat that are not evident from changes in body weight.

Pasteurella multocida: from Zoonosis to Cellular Microbiology

PubMed Central

Ho, Mengfei

2013-01-01

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

The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum.

PubMed Central

Leibovich, S. J.; Ross, R.

1975-01-01

The role of the monocyte/macrophage in wound repair has been investigated by studying the healing process in wounds depleted of this cell and/or its phagocytic activity. Hydrocortisone acetate (0.6 mg/g body weight) administered as a subcutaneous depot was used to induce a prolonged monocytopenia in guinea pigs, and antimacrophage serum (AMS) was used for local elimination of tissue macrophages. In vitro, the presence of complement, macrophages are rapidly lysed and used killed by AMS. In the absence of complement, AMS is not cytotoxic but potently inhibits adherence to and phagocytosis of opsonized erythrocytes by macrophages. AMS titers were obtained by observation of adherence and phagocytosis of opsonized erythrocytes in serial dilutions of AMS. Six groups of animals were studied: a) untreated animals, b)animals receiving daily subcutaneous injections of normal rabbit serum (NRS) around each wound, c)animals receiving daily subcutaneous AMS around each wound, d)animals receiving systemic hydrocortisone, e)animals receiving systemic hydrocortisone and daily injections of NRS around each wound, and f)animals receiving systemic hydrocortisone and daily AMS around each wound. Wounds consisted of a series of six linear incisions in the dorsal skin. Subcutaneous AMS alone has no effect on the number of circulating monocytes, nor was there any observable effect on the number or the phagocytic ability of wound macrophages. Fibrosis in these wounds was unaffected. Systemic hydrocortisone induced a prolonged monocytopenia. The macrophage level in the wounds of these monocytopenic animals was reduced to approximately one-third that of controls; the phagocytic activity of the monocytes/macrophages that did appear in these wounds was, however, similar to that of controls. Some inhibition of wound debridement was observed in these wounds, but fibrosis was virtually unaffected. Collagen synthesis, as judged morphometrically, was similar to that of control wounds at all stages of repair. Conjoint systemic hydrocortisone and subcutaneous AMS around each wound resulted in the almost complete disappearance of macrophages from the wounds. Wound fibrin levels were elevated, and clearance of fibrin, neutrophils, erythrocytes and other miscellaneous debris from these wounds was delayed. Fibroblasts, which in control wounds first appear by 3 days postwounding and reach maximal levels by day 5, did not appear in these wounds until day 5, and their subsequent rate of proliferation was slower than that of controls. Continued. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 PMID:1109560

Biocompatibility and Biocorrosion of Hydroxyapatite-Coated Magnesium Plate: Animal Experiment.

PubMed

Lim, Ho-Kyung; Byun, Soo-Hwan; Woo, Jae-Man; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Bong-Ju; Kim, Hyoun-Ee; Lee, Jung-Woo; Kim, Soung-Min; Lee, Jong-Ho

2017-09-30

Magnesium (Mg) has the advantage of being resorbed in vivo, but its resorption rate is difficult to control. With uncontrolled resorption, Magnesium as a bone fixation material has minimal clinical value. During resorption not only is the strength rapidly weakened, but rapid formation of metabolite also occurs. In order to overcome these disadvantages, hydroxyapatite (HA) surface coating of pure magnesium plate was attempted in this study. Magnesium plates were inserted above the frontal bone of Sprague-Dawley rats in both the control group (Bare-Mg group) and the experimental group (HA-Mg group). The presence of inflammation, infection, hydrogen gas formation, wound dehiscence, and/or plate exposure was observed, blood tests were performed, and the resorption rate and tensile strength of the retrieved metal plates were measured. The HA-Mg group showed no gas formation or plate exposure until week 12. However, the Bare-Mg group showed consistent gas formation and plate exposure beginning in week 2. WBC (White Blood Cell), BUN (Blood Urea Nitrogen), Creatinine, and serum magnesium concentration levels were within normal range in both groups. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) values, however, were above normal range in some animals of both groups. The HA-Mg group showed statistically significant advantage in resistance to degradation compared to the Bare-Mg group in weeks 2, 4, 6, 8, and 12. Degradation of HA-Mg plates proceeded after week 12. Coating magnesium plates with hydroxyapatite may be a viable method to maintain their strength long enough to allow bony healing and to control the resorption rate during the initial period.

Biocompatibility and Biocorrosion of Hydroxyapatite-Coated Magnesium Plate: Animal Experiment

PubMed Central

Woo, Jae-Man; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Hyoun-Ee; Lee, Jung-Woo; Lee, Jong-Ho

2017-01-01

Magnesium (Mg) has the advantage of being resorbed in vivo, but its resorption rate is difficult to control. With uncontrolled resorption, Magnesium as a bone fixation material has minimal clinical value. During resorption not only is the strength rapidly weakened, but rapid formation of metabolite also occurs. In order to overcome these disadvantages, hydroxyapatite (HA) surface coating of pure magnesium plate was attempted in this study. Magnesium plates were inserted above the frontal bone of Sprague-Dawley rats in both the control group (Bare-Mg group) and the experimental group (HA-Mg group). The presence of inflammation, infection, hydrogen gas formation, wound dehiscence, and/or plate exposure was observed, blood tests were performed, and the resorption rate and tensile strength of the retrieved metal plates were measured. The HA-Mg group showed no gas formation or plate exposure until week 12. However, the Bare-Mg group showed consistent gas formation and plate exposure beginning in week 2. WBC (White Blood Cell), BUN (Blood Urea Nitrogen), Creatinine, and serum magnesium concentration levels were within normal range in both groups. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) values, however, were above normal range in some animals of both groups. The HA-Mg group showed statistically significant advantage in resistance to degradation compared to the Bare-Mg group in weeks 2, 4, 6, 8, and 12. Degradation of HA-Mg plates proceeded after week 12. Coating magnesium plates with hydroxyapatite may be a viable method to maintain their strength long enough to allow bony healing and to control the resorption rate during the initial period. PMID:28973984

Tomato (Lycopersicon esculentum) Supplementation Induces Changes in Cardiac miRNA Expression, Reduces Oxidative Stress and Left Ventricular Mass, and Improves Diastolic Function.

PubMed

Pereira, Bruna L B; Arruda, Fernanda C O; Reis, Patrícia P; Felix, Tainara F; Santos, Priscila P; Rafacho, Bruna P; Gonçalves, Andrea F; Claro, Renan T; Azevedo, Paula S; Polegato, Bertha F; Okoshi, Katashi; Fernandes, Ana A H; Paiva, Sergio A R; Zornoff, Leonardo A M; Minicucci, Marcos F

2015-11-19

The aim of this study was to evaluate the effects of tomato supplementation on the normal rat heart and the role of oxidative stress in this scenario. Male Wistar rats were assigned to two groups: a control group (C; n = 16), in which animals received a control diet + 0.5 mL of corn oil/kg body weight/day, and a tomato group (T; n = 16), in which animals received a control diet supplemented with tomato +0.5 mL of corn oil/kg body weight/day. After three months, morphological, functional, and biochemical analyses were performed. Animals supplemented with tomato had a smaller left atrium diameter and myocyte cross-sectional area (CSA) compared to the control group (C group: 474 (415-539); T group: 273 (258-297) µm²; p = 0.004). Diastolic function was improved in rats supplemented with tomato. In addition, lipid hydroperoxide was lower (C group: 267 ± 46.7; T group: 219 ± 23.0 nmol/g; p = 0.039) in the myocardium of rats supplemented with tomato. Tomato intake was also associated with up-regulation of miR-107 and miR-486 and down-regulation of miR-350 and miR-872. In conclusion, tomato supplementation induces changes in miRNA expression and reduces oxidative stress. In addition, these alterations may be responsible for CSA reduction and diastolic function improvement.

Foot-and-mouth disease: past, present and future

PubMed Central

2013-01-01

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions. PMID:24308718

Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease

PubMed Central

Redgrave, Peter; Rodriguez, Manuel; Smith, Yoland; Rodriguez-Oroz, Maria C.; Lehericy, Stephane; Bergman, Hagai; Agid, Yves; DeLong, Mahlon R.; Obeso, Jose A.

2011-01-01

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson’s disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson’s disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. PMID:20944662

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca 2+ ] i transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca 2+ waves. These proarrhythmic manifestations, related to Ca 2+ /calmodulin-dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Decreased sensitivity to thermal pain in rats bred for high anxiety-related behaviour is attenuated by citalopram or diazepam treatment.

PubMed

Jochum, Thomas; Boettger, Michael Karl; Wigger, Alexandra; Beiderbeck, Daniela; Neumann, Inga D; Landgraf, Rainer; Sauer, Heinrich; Bär, Karl-Jürgen

2007-10-01

Complex interactions between pain perception, anxiety and depressive symptoms have repeatedly been described. However, pathophysiological or biochemical mechanisms underlying the alterations of pain perception in patients suffering from anxiety or depression still remain a matter of debate. Thus, we aimed to perform an investigation on pain perception in an animal model of extremes in anxiety-related behaviour, which might provide a tool for future studies. Here, thermal pain thresholds were obtained from rats with a genetic predisposition to high anxiety-related behaviour (HAB), including signs of comorbid depression-like behaviour and from controls (low-anxiety rats (LAB); cross-bred HAB and LAB rats; Wistar rats). Furthermore, the effect of eight-week antidepressive treatment using citalopram and of short-term anxiolytic treatment with diazepam on pain-related behaviour was assessed. Simultaneously, anxiety-related behaviour was monitored. At baseline, HAB animals showed 35% higher thresholds for thermal pain than controls. These were normalized to control levels after eight weeks of continuous citalopram treatment paralleled by a reduction of anxiety-related behaviour, but also acutely after diazepam administration. Overall, thermal pain thresholds in HAB animals are shifted in a similar fashion as seen in patients suffering from major depressive disorder. Antidepressive, as well as anxiolytic treatments, attenuated these differences. As the relative importance of the factors anxiety and depression cannot be derived from this study with certainty, extending these investigations to additional animal models might represent a valuable tool for future investigations concerning the interrelations between anxiety, depression, and pain at a molecular level.

Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells.

PubMed

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy

2010-10-01

The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30-35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.

Red spinach (Amaranthus tricolor L.) ethanolic extract as prevention against atherosclerosis based on the level of Low-Density Lipoprotein and histopathological feature of aorta in male Sprague-Dawley rats

NASA Astrophysics Data System (ADS)

Pradana, Dimas Adhi; Pondawinata, Marizki; Widyarini, Sitarina

2017-03-01

This study aimed to determine the potential activity of standardized ethanolic extract of red spinach as prevention against atherosclerosis based on the level of Low-Density Lipoprotein (LDL) and histopathological feature of aorta in male Sprague-Dawley rats induced by high-fat, high-cholesterol diet. A total of 42 animals was divided into 6 groups: normal control group, negative control group, positive control group (0.9 mg/kgBW of simvastatin), first intervention group (200 mg/kgBW of red spinach extract), second intervention group (400 mg/kgBW of red spinach extract), and third intervention group (800 mg/kgBW of red spinach extract). From the first day up to the 66th day, all the groups, except the normal control group and negative control group, were administered simvastatin (positive control) and extract of amaranth (intervention). Then, from the eighth day until Day 66, induction of high-fat and high-cholesterol diet was given in two hours after the simvastatin and red spinach extract administration. The determination of LDL parameters was conducted on Day 0, Day 35, and Day 67. On the 67th day, the animals were dissected to examine the aortic histopathological parameters. The results showed that the ethanolic extract of red spinach with a dose of 200 mg/kgBW, 400 mg/kgBW, and 800 mg/kgBW statistically demonstrated a significant difference (p<0.05). The histopathological feature of the aorta in the treatment indicated the absence of fat in the blood vessel walls or even of foam cells supporting thereby the result of LDL level. This means there was a significant effect of ethanolic extract of red spinach on the prevention against atherosclerosis based on the level of Low-Density Lipoprotein and the histopathological feature of aorta in male Sprague-Dawley rats.

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

Schwartz, C.; Gavin, P.

This report describes research performed at the WSU College of Veterinary Medicine in which a large animal model was developed and used to study the effects of boron neutron capture therapy (BNCT) on normal and neoplastic canine brain tissue. The studies were performed using borocaptate sodium (BSH) and epithermal neutrons and had two major foci: biodistribution of BSH in animals with spontaneously occurring brain tumors; and effects of BNCT in normal and neoplastic brain tissue.

Image analysis for estimating the weight of live animals

NASA Astrophysics Data System (ADS)

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

1991-02-01

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

Erythropoietin administration facilitates return of spontaneous circulation and improves survival in a pig model of cardiac arrest.

PubMed

Vasileiou, Panagiotis V S; Xanthos, Theodoros; Barouxis, Dimitrios; Pantazopoulos, Charalampos; Papalois, Apostolos E; Lelovas, Paulos; Kotsilianou, Olympia; Pliatsika, Paraskevi; Kouskouni, Evaggelia; Iacovidou, Nicoletta

2014-08-01

In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021). Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables. Copyright © 2014 Elsevier Inc. All rights reserved.

Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

PubMed Central

Adeniyi, Philip Adeyemi; Olatunji, Babawale Peter; Ishola, Azeez Olakunle; Ajonijebu, Duyilemi Chris; Ogundele, Olalekan Michael

2014-01-01

This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n = 5; control) received normal saline. The total duration of treatment for all groups was 28 days (P28–P56). At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory. PMID:25477708

Anti-diabetic effects of Sargassum oligocystum on Streptozotocin-induced diabetic rat.

PubMed

Akbarzadeh, Samad; Gholampour, Hossein; Farzadinia, Parviz; Daneshi, Adel; Ramavandi, Bahman; Moazzeni, Ali; Keshavarz, Mojtaba; Bargahi, Afshar

2018-03-01

Diabetes is a metabolic syndrome which is associated with the worldwide major public health problems. There are many natural compounds from the sea-market, as a valuable aquatic source, along with the variety of health and therapeutic benefits. In the present research, with respect to the traditional and ethnic uses of Sargassum oligocystum algae for healing of some diseases which have similar metabolic mechanism to the diabetes, its anti-diabetic effects in animal model was proposed. The animals (rat) were divided into the normal control, diabetic control, positive control and, the test groups. The test groups were gavaged with oral doses of 150 and 300 mg/kg of algae hydroalcoholic extracts. After 30 days of intervention the serum glucose, cholesterol, triglyceride, HDL C , LDL C , insulin, insulin resistance, β-cells function and, the histopathology of pancreatic tissue were evaluated. In animals that were fed with algae extracts a significant decrease in the fasting blood glucose, triglyceride and HOMA-IR and an increase in the HOMA-B with no significant impacts on the insulin, cholesterol and HDL were observed. Also, the histopathology evaluations in the groups which were treated with algae extract revealed the regeneration and reconstitution of damaged pancreatic β-cells. The results give evidence that, the S. oligocystum algae extract has a healing effect on diabetes which can be considered as a new research prospect for the natural therapy of diabetes.

Neurotoxicity of misonidazole in rats following intravenous administration.

PubMed

Graziano, M J; Henck, J W; Meierhenry, E F; Gough, A W

1996-06-01

Misonidazole is a hypoxic cell radiosensitizer that induces a peripheral neuropathy in humans after exceeding a schedule-dependent cumulative threshold dose. Clinical studies of misonidazole have been conducted using oral administration, whereas most other radiosensitizers have been administered intravenously. Since route of exposure can potentially influence the toxicity of xenobiotics, the objective of this study was to assess the neurotoxicity of misonidazole in rats following intravenous dosing using a battery of routine clinical, neurofunctional, biochemical, and histopathologic screening methods. Male Sprague-Dawley rats were administered intravenous doses of misonidazole at 0 (vehicle control), 100, 200, 300, or 400 mg kg-1 once per day, 5 days per week, for 2 weeks. Animals were evaluated for neurofunctional and pathological changes following termination of treatment (Days 15-17) and at the end of a 4 week observation period (Days 43-45). During the dosing phase, hypoactivity, salivation, rhinorrhea, chromodacryorrhea, rough pelage and ataxia were observed at 400 mg kg-1, and body weight gain of the 300 and 400 mg kg-1 groups was significantly decreased relative to the vehicle controls by 24% and 49%, respectively. Corresponding reductions in food consumption were 8% and 23%, respectively. Although most 400 mg kg-1 animals appeared normal on Day 15 prior to the neurofunctional evaluations, rotorod testing precipitated a number of clinical signs including: ataxia, impaired righting reflex, excessive rearing, tremors, vocalization, circling, head jerking, excessive sniffing and hyperactivity. All of these animals recovered and appeared normal from Day 17 through study termination. There were no treatment-related effects on motor activity, acoustic startle response, rotorod performance, forelimb group strength, toe and tail pinch reflexes, tibial nerve beta-glucuronidase activity or tail nerve conduction velocity. Although hindlimb grip strength of the 400 mg kg-1 group was significantly decreased by 17% relative to the vehicle controls on Day 15, this finding appeared related to the reduced food consumption and body weight gain in these animals. No microscopic changes were detected in peripheral nerves. Necrosis and proliferation of fibrillary astrocytes (gliosis) were seen in the cerebellum and medulla of the 400 mg kg-1 animals on Day 16. Gliosis in these same brain regions was observed in the 300 and 400 mg kg-1 groups on Day 44. The results show that intravenous administration of misonidazole to rats causes dose-limiting central nervous system toxicity without effects on peripheral nervous tissue. The lack of peripheral neurotoxicity was most likely due to a combination of several interrelated factors including route of administration, duration and intensity of the dosing regimen, and total cumulative dose.

Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

PubMed

Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

2015-01-01

In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

PubMed

Yosida, Shigeto; Okanoya, Kazuo

2012-02-01

Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

Effect of alpha-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats.

PubMed

Vasavi, H; Thangaraju, M; Sachdanandam, P

1994-02-23

The anticarcinogenic activity of alpha-tocopherol (Vitamin E) was tried in fibrosarcoma induced rats through its antioxidative potential. The rate of formation of malondialdehyde (MDA), the end product of lipid peroxidation was analysed in alpha-tocopherol (400 mg/kg body weight) treated and untreated fibrosarcoma bearing rats with respective controls. The levels of non-enzymic antioxidants like, glutathione and vitamin E, and enzymic antioxidants viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST) were assayed as well. Significantly increased (p < 0.001) level of lipid peroxide was observed with concomitant decreases in the level of enzymic and non-enzymic antioxidants in fibrosarcoma bearing rats when compared with control animals. In alpha-tocopherol supplemented animals, the corrected level of these parameters were observed likely to near normal values. Thus, alpha-tocopherol can be accepted to pose first line of defense mechanism against excessively formed reactive species due to impaired antioxidant systems in fibrosarcoma conditions, that cause membrane damage leading to deleterious effects.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

PubMed

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

2013-11-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

SUBCLINICAL INFECTION OF DOGS BY CANINE-ADAPTED MEASLES VIRUS EVIDENCED BY THEIR SUBSEQUENT IMMUNITY TO CANINE DISTEMPER VIRUS

PubMed Central

Moura, Roberto A.; Warren, Joel

1961-01-01

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702–705. 1961.—Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time. PMID:14476677

Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme.

PubMed Central

Masferrer, J L; Seibert, K; Zweifel, B; Needleman, P

1992-01-01

The effect of endogenous glucocorticoids on the expression of the cyclooxygenase enzyme was studied by contrasting cyclooxygenase expression and prostanoid synthesis in adrenalectomized and sham-adrenalectomized mice with or without the concurrent administration of endotoxin. Peritoneal macrophages obtained from adrenalectomized mice showed a 2- to 3-fold induction in cyclooxygenase synthesis and activity when compared to sham controls. Intravenous injection of a sublethal dose of endotoxin (5 micrograms/kg) further stimulated cyclooxygenase synthesis, resulting in a 4-fold increase in prostaglandin production. Similar cyclooxygenase induction can be achieved in macrophages obtained from normal mice but only after high doses of endotoxin (2.5 mg/kg) that are 100% lethal to adrenalectomized mice. Restoration of glucocorticoids in adrenalectomized animals with dexamethasone completely inhibited the elevated cyclooxygenase and protected these animals from endotoxin-induced death. In contrast, no signs of cyclooxygenase induction were observed in the kidneys of the adrenalectomized mice, even when treated with endotoxin. Dexamethasone did not affect the constitutive cyclooxygenase activity and prostaglandin production present in normal and adrenalectomized kidneys. These data indicate the existence of a constitutive cyclooxygenase that is normally present in most cells and tissues and is unaffected by steroids and of an inducible cyclooxygenase that is expressed only in the context of inflammation by proinflammatory cells, like macrophages, and that is under glucocorticoid regulation. Under normal physiological conditions glucocorticoids maintain tonic inhibition of inducible cyclooxygenase expression. Depletion of glucocorticoids or the presence of an inflammatory stimulus such as endotoxin causes rapid induction of this enzyme, resulting in an exacerbated inflammatory response that is often lethal. Images PMID:1570314

Linkage mapping of a mouse gene, iv, that controls left-right asymmetry of the heart and viscera.

PubMed Central

Brueckner, M; D'Eustachio, P; Horwich, A L

1989-01-01

Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex). Images PMID:2740340

Is eye damage caused by stereoscopic displays?

NASA Astrophysics Data System (ADS)

Mayer, Udo; Neumann, Markus D.; Kubbat, Wolfgang; Landau, Kurt

2000-05-01

A normal developing child will achieve emmetropia in youth and maintain it. Thereby cornea, lens and axial length of the eye grow astonishingly coordinated. In the last years research has evidenced that this coordinated growing process is a visually controlled closed loop. The mechanism has been studied particularly in animals. It was found that the growth of the axial length of the eyeball is controlled by image focus information from the retina. It was shown that maladjustment can occur by this visually-guided growth control mechanism that result in ametropia. Thereby it has been proven that e.g. short-sightedness is not only caused by heredity, but is acquired under certain visual conditions. It is shown that these conditions are similar to the conditions of viewing stereoscopic displays where the normal accommodation convergence coupling is disjoint. An evaluation is given of the potential of damaging the eyes by viewing stereoscopic displays. Concerning this, different viewing methods for stereoscopic displays are evaluated. Moreover, clues are given how the environment and display conditions shall be set and what users shall be chosen to minimize the risk of eye damages.

Modified natural clinoptilolite detoxifies small mammal's organism loaded with lead II: genetic, cell, and physiological effects.

PubMed

Topashka-Ancheva, Margarita; Beltcheva, Michaela; Metcheva, Roumiana; Rojas, J Antonio Heredia; Rodriguez-De la Fuente, Abraham O; Gerasimova, Tsvetelina; Rodríguez-Flores, Laura E; Teodorova, Svetla E

2012-06-01

The detoxification capacity of the clinoptilolite modification KLS-10-MA used as food additive in small mammals, chronically lead-exposed, was proven for the first time. The modified clinoptilolite was prepared based on natural Bulgarian clinoptilolite deposits. As a powder, it was mechanically mixed at 12.5% concentration with the conventional forage for small rodents. Lead in the form of aqueous solution of Pb(NO(3))(2) was diluted in the drinking water. In the ecotoxicological experiment covering 90 days, imprinting control region laboratory mice were used. They were allocated into four groups: group 1, (control): animals fed with conventional food for small rodents and water; group 2: animals fed with conventional food + clinosorbent KLS-10-MA and water; group 3: animals fed with conventional food and water + Pb(NO(3))(2); and group 4: animals fed with conventional food + KLS-10-MA and water + Pb(NO(3))(2). A group of non-exposed healthy animals was fed with conventional forage mixed with KLS-10-MA to prove eventual toxicity of the sorbent and influence on growth performance. The changes in the chromosome structure, mitotic index, erythrocyte form, erythropoiesis, and body weight gain were recorded. On day 90, the following relations were established: Pb-exposed and clinoptilolite-supplemented mice exhibited 2.3-fold lower chromosome aberrations frequency, 2.5-fold higher mitotic index, and 1.5-fold higher percentage normal erythrocytes 1.3-fold higher body weight compared to Pb-exposed and unsupplemented animals. The obtained data showed that the sorbent is practically non-toxic. The results of the present study encourage a further elaboration of a reliable drug based on the tested substance in the cases of chronic lead intoxication.

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

PubMed

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

2015-09-01

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

Method for Correction of Consequences of Radiation-Induced Heart Disease using Low-Intensity Electromagnetic Emission under Experimental Conditions.

PubMed

Bavrina, A P; Monich, V A; Malinovskaya, S L; Yakovleva, E I; Bugrova, M L; Lazukin, V F

2015-05-01

Effects of successive exposure to ionizing irradiation and low-intensity broadband red light on electrical activity of the heart and myocardium microstructure were studied in rats. Lowintensity red light corrected some ECG parameters, in particular, it normalized QT and QTc intervals and voltage of R and T waves. Changes in ECG parameters were followed by alterations in microstructure of muscle fi laments in the myocardium of treatment group animals comparing to control group.

Protective Role of Eosinophils and TNFa after Ozone Inhalation.

PubMed

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

2017-03-01

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

Therapeutic effect of low molecular weight chitosan containing sepia ink on ethanol-induced gastric ulcer in rats.

PubMed

Zhang, Wei; Liu, Kang; Li, Lei; Li, Yingxin; Sui, Xianxian; Rao, Yinzhu; Wu, Jiahao; Wu, Qiuping

2016-12-01

To evaluate the role of low molecular chitosan containing sepia ink (LMCS) in ethanol-induced (5 ml/kg) gastric ulcer in rats. Animals were divided into four groups (n = 12): normal group (Normal), negative control group (Con), experiment group (LMCS) and positive control Omeprazole group (OMZ). Gastric empty rate was detected in the first 7 days. Rats were sacrificed at 7, 14 and 21 day for histology and ELISA detections. Gastric empty was no significant differences among the groups (P > 0.05). Histological observation showed gastric mucosal LMCS treated had better healing effect. Hydroxyproline (Hyp) was significantly increased from 7 day (P < 0.05). LMCS significantly inhibited malondialdehyde (MDA) generation for lipid peroxidation from 7 day (P < 0.05). LMCS significantly promoted the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) at the earlier stage (P < 0.05). OMZ had the similar effects above. As for myeloperoxidase (MPO), LMCS significantly decreased and restored it to normal levels from 7 day (P < 0.05), it is earlier than OMZ which is from 14 day. LMCS can improve gastric mucosa tissue repair, exert significant influences on oxidative and antioxidant enzyme activities and neutrophil infiltration.

Repaglinide, glibenclamide and glimepiride administration to normal and hereditarily diabetic rats.

PubMed

Ladrière, L; Malaisse-Lagae, F; Fuhlendorff, J; Malaisse, W J

1997-09-24

Repaglinide (1 microg/g body wt), glibenclamide (10 microg/g) or glimepiride (10 microg/g) were administered orally to either fed or overnight fasted normal rats and hereditarily diabetic animals (GK rats). In both fed and starved normal rats, repaglinide provoked a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than those observed after administration of the hypoglycemic sulfonylureas. Likewise, in fed GK rats, the plasma insulin concentration was already increased by 30.0 +/- 1.6% 15 min after administration of repaglinide, whilst a sizeable insulinotropic action of the sulfonylureas was only recorded at much later times. Except for a lower glycemia at the 240th min of the test, there was little to distinguish, in starved GK rats, between control experiments including the oral administration of the solution of carboxymethylcellulose used as vehicle and the experiments conducted with the antidiabetic agents. Several converging observations indicated that glimepiride stimulated insulin release more promptly than glibenclamide. It is proposed that advantage can be taken from these vastly different time-courses of the hormonal and metabolic response to distinct hypoglycemic agents to optimize the control of glucose homeostasis in non-insulin-dependent diabetic subjects.

The metabolic and endocrine response and health implications of consuming sugar-sweetened beverages: findings from recent randomized controlled trials.

PubMed

Rippe, James M

2013-11-01

Fructose-containing sugars, including fructose itself, high fructose corn syrup (HFCS), and sucrose have engendered considerable controversy. The effects of HFCS and sucrose in sugar-sweetened beverages, in particular, have generated intense scientific debate that has spilled over to the public. This controversy is related to well-known differences in metabolism between fructose and glucose in the liver. In addition, research studies have often been conducted comparing pure fructose and pure glucose even though neither is consumed to any appreciable degree in isolation in the human diet. Other evidence has been drawn from animal studies and epidemiologic or cohort studies. Few randomized controlled trials (RCTs) have compared HFCS with sucrose (the 2 sugars most commonly consumed in the human diet) at dosage amounts within the normal human consumption range. This review compares results of recently concluded RCTs with other forms of evidence related to fructose, HFCS, and sucrose. We conclude that great caution must be used when suggesting adverse health effects of consuming these sugars in the normal way they are consumed and at the normal amounts in the human diet, because RCTs do not support adverse health consequences at these doses when employing these sugars.

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Circulating parathyroid hormone and calcitonin in rats after spaceflight

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

1992-01-01

Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

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.

Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

PubMed

Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

2016-03-01

Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

A study of the intrarenal recycling of urea in the rat with chronic experimental pyelonephritis.

PubMed Central

Gilbert, R M; Weber, H; Turchin, L; Fine, L G; Bourgoignie, J J; Bricker, N S

1976-01-01

The concentrating ability of the kidney was studied by clearance and micropuncture techniques and tissue slice analyses in normal rats with two intact kidneys (intact controls), normal rats with a solitary kidney (uninephrectomized controls), and uremic rats with a single pyelonephritic kidney. Urinary osmolality after water deprivation for 24 h and administration of antidiuretic hormone was 2,501+/-217 and 2,874+/-392 mosmol/kg H2O in intact and uninephrectomized control rats, respectively, and 929+/-130 mosmol/kg H2O in pyelonephritic rats (P less than 0.001 compared to each control group). Fractional water reabsorption and concentrating ability were significantly decreased in the pyelonephritic group, and, to achieve an equivalent fractional excretion of urea, a greater fractional excretion of water was required in the pyelonephritic rats than in the control rats. Whole animal glomerular filtration rate was 1.57+/-0.19 ml/min and 1.39+/-0.18 ml/min in intact and in uninephrectomized controls, respectively, and 0.30+/-0.07 ml/min in pyelonephritic rats (P less than 0.001 compared to each control group). Single nephron glomerular filtration rate was 35.6+/-3.8 nl/min in intact control rats and was significantly increased (P less than 0.05) in both uninephrectomized (88.0+/-10.8 nl/min) and pyelonephritic rats (71.5+/-14.4 nl/min). In all groups fractional water delivery and fractional sodium delivery were closely comparable at the end of the proximal convoluted tubule and at the beginning of the distal convoluted tubule. In contrast, fractional urea delivery out of the proximal tubule was greater in the intact control group (73+/-8%) than in either the uninephrectomized (52+/-2%) or the pyelonephritic group (53+/-3%) (P less than 0.005). Fractional urea delivery at the early part of the distal tubule increased significantly to 137+/-11% and 93+/-6% of the filtered load in intact control and uninephrectomized control rats, respectively (P less than 0.001 compared to the late proximal values of each group), but failed to increase significantly in pyelonephritic rats (65+/-13%), indicating interruption of the normal recycling of urea in the latter group. Analysis of tissue slices demonstrated a rising corticopapillary gradient for total tissue water solute concentration as well as for tissue water urea concentration in both groups of control rats. In contrast, the pyelonephritic animals exhibited no similar gradients from cortex to papilla. These data indicate that the pyelonephritic kidney fails to recycle urea and accumulate interstitial solute. The latter must inevitably lead to a concentrating defect. Images PMID:993348

Recent advances in the cell biology of aging.

PubMed

Hayflick, L

1980-01-01

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

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

PubMed

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Anti-inflammatory Effect of Amitriptyline on Ulcerative Colitis in Normal and Reserpine-Induced Depressed Rats

PubMed Central

Fattahian, Ehsan; Hajhashemi, Valiollah; Rabbani, Mohammad; Minaiyan, Mohsen; Mahzouni, Parvin

2016-01-01

Depressive disorders are more common among persons with chronic diseases such as inflammatory bowel disease and anti-inflammatory effect of some antidepressants such as amitriptyline has been reported. Acetic acid colitis was induced in both reserpinised (depressed) and non-reserpinised (normal) rats. Reserpinised groups received reserpine (6 mg/kg, i.p.) one hour prior to colitis induction. Then Amitriptyline (5, 10, 20 mg/kg, i.p.) was administered to separate groups of male Wistar rats. All treatments were carried out two hours after colitis induction and continued daily for four days. Dexamethasone (1 mg/kg) and normal saline (1 mL/kg) were used in reference and control groups, respectively. At day five, animals were euthanized and colonic tissue injuries were assessed macroscopically and pathologically. Myeloperoxidase activity as a marker of neutrophil infiltration was also measured in colonic tissues. Results showed that reserpine (6 mg/kg, i.p.) intensified colitic condition. Compared to control, amitriptyline (10, 20 mg/kg) and dexamethasone significantly decreased weight of colon and ulcer index in normal and reserpine-induced depressed rats. Myeloperoxidase activity and pathological assessments also proved anti-inflammatory effect of amitriptyline. Our results suggest that amitriptyline, a tricyclic antidepressant, could reduce inflammatory and ulcerative injuries of colon both in normal and depressed rats. So among the wide spread anti-depressant drugs, amitriptyline is a good choice to treat depression comorbidities in patients with IBD. PMID:28228811

Culture-expanded mesenchymal stem cell sheets enhance extraction-site alveolar bone growth: An animal study.

PubMed

Mu, S; Tee, B C; Emam, H; Zhou, Y; Sun, Z

2018-04-06

Impaired bone formation of the buccal alveolar plate after tooth extraction during adolescence increases the difficulty of future implant restoration. This study was undertaken to assess the feasibility and efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local bone growth. Mandibular bone marrow was aspirated from 3-month-old pigs (n = 5), from which MSCs were isolated and culture expanded. Triple-layer MSC sheets were then fabricated using temperature-responsive tissue culture plates. One month after bone marrow aspirations, the same pigs underwent bilateral extraction of mandibular primary molars, immediately followed by transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal buccal alveolar surface of 1 randomly chosen side. The contralateral side (control) underwent the same periosteal reflection surgery without receiving MSC sheet transplantation. Six weeks later, the animals were killed and specimens from both sides were immediately harvested for radiographic and histological analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral apposition and bone volume fraction (BV/TV) were quantified and compared between the MSC sheet and control sides using paired t-tests. Triple-layer MSC sheets were reliably fabricated and the majority of cells remained vital before transplantation. The thickness of buccal bone tended to increase with MSC sheet transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 ± 0.73 mm thicker bone on the MSC sheet side than the control side. After being normalized by the TMD of intracortical bone, the TMD of surface cortical bone was 0.5-fold higher on the MSC sheet side than the control side (P < .05). Likewise, the BV/TV measurements of the buccal surface region were also 0.4-fold higher on the MSC sheet side than the control side (P < .05) after being normalized by measurements from the intracortical region. Mineral apposition measurements were not different between the 2 sides. Mandibular marrow-derived MSCs can be fabricated into cell sheets and autogenous transplantation of MSC sheets onto the subperiosteal buccal alveolar bone surface at the tooth-extraction site may increase local bone density. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exploring the Anti-quorum Sensing and Antibiofilm Efficacy of Phytol against Serratia marcescens Associated Acute Pyelonephritis Infection in Wistar Rats

PubMed Central

Srinivasan, Ramanathan; Mohankumar, Ramar; Kannappan, Arunachalam; Karthick Raja, Veeramani; Archunan, Govindaraju; Karutha Pandian, Shunmugiah; Ruckmani, Kandasamy; Veera Ravi, Arumugam

2017-01-01

Quorum Sensing (QS) mechanism, a bacterial density-dependent gene expression system, governs the Serratia marcescens pathogenesis through the production of virulence factors and biofilm formation. The present study demonstrates the anti-quorum sensing (anti-QS), antibiofilm potential and in vivo protective effect of phytol, a diterpene alcohol broadly utilized as food additive and in therapeutics fields. In vitro treatment of phytol (5 and 10 μg/ml) showed decreasing level of biofilm formation, lipase and hemolysin production in S. marcescens compared to their respective controls. More, microscopic analyses confirmed the antibiofilm potential of phytol. The biofilm related phenomenons such as swarming motility and exopolysccharide productions were also inhibited by phytol. Furthermore, the real-time analysis elucidated the molecular mechanism of phytol which showed downregulation of fimA, fimC, flhC, flhD, bsmB, pigP, and shlA gene expressions. On the other hand, the in vivo rescue effect of phytol was assessed against S. marcescens associated acute pyelonephritis in Wistar rat. Compared to the infected and vehicle controls, the phytol treated groups (100 and 200 mg/kg) showed decreased level of bacterial counts in kidney, bladder tissues and urine samples on the 5th post infection day. As well, the phytol treatment showed reduced level of virulence enzymes such as lipase and protease productions compared to the infected and vehicle controls. Further, the infected and vehicle controls showed increasing level of inflammatory markers such as malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) productions. In contrast, the phytol treatment showed decreasing level of inflammatory markers. In histopathology, the uninfected animal showed normal kidney and bladder structure, wherein, the infected animals showed extensive infiltration of neutrophils in kidney and bladder tissues. In contrast, the phytol treatment showed normal kidney and bladder tissues. Additionally, the toxic effect of phytol (200 mg/kg) was assessed by single dose toxicity analysis. No changes were observed in hematological, biochemical profiles and histopathological analysis of vital organs in phytol treated animals compared to the untreated controls. Hence, this study suggested the potential use of phytol for its anti-QS, antibiofilm and anti-inflammatory properties against S. marcescens infections and their associated inflammation reactions. PMID:29259923

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats

PubMed Central

Alabi, A. S.; Omotoso, Gabriel O.; Enaibe, B. U.; Akinola, O. B.; Tagoe, C. N. B.

2013-01-01

Background: This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. Materials and Methods: The animals used for the study were grouped into three: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Results: Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Conclusion: Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions. PMID:23798793

Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model.

PubMed

Staber, Janice M; Pollpeter, Molly J

2016-01-01

Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p < 0.0001). In addition, the hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.

Ecological theory as a foundation to control pathogenic invasion in aquaculture

PubMed Central

De Schryver, Peter; Vadstein, Olav

2014-01-01

Detrimental host–pathogen interactions are a normal phenomenon in aquaculture animal production, and have been counteracted by prophylactic use of antibiotics. Especially, the youngest life stages of cultivated aquatic animals are susceptible to pathogen invasion, resulting in disease and mortality. To establish a more sustainable aquatic food production, there is a need for new microbial management strategies that focus on ‘join them' and not the traditional ‘beat them' approaches. We argue that ecological theory could serve as a foundation for developing sustainable microbial management methods that prevent pathogenic disease in larviculture. Management of the water microbiota in aquaculture systems according to ecological selection principles has been shown to decrease opportunistic pathogen pressure and to result in an improved performance of the cultured animals. We hypothesize that manipulation of the biodiversity of the gut microbiota can increase the host's resistance against pathogenic invasion and infection. However, substantial barriers need to be overcome before active management of the intestinal microbiota can effectively be applied in larviculture. PMID:24892581

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.

Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity.

PubMed

Aruna, K; Rukkumani, R; Varma, P Suresh; Menon, Venugopal P

2005-05-01

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.

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

PubMed

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

2012-02-01

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

[Glycoproteins of mucus of gastric and duodenal wall surface during ulcerogenesis and the impact of fenugreek].

PubMed

Khil'ko, T D; Iakubtsova, I V; Preobrazhens'ka, T D; Ostapchenko, L I

2013-01-01

The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats.

Microalgal Oil Supplementation Has an Anti-Obesity Effect in C57BL/6J Mice Fed a High Fat Diet

PubMed Central

Yook, Jin-Seon; Kim, Kyung-Ah; Park, Jeong Eun; Lee, Seon-Hwa; Cha, Youn-Soo

2015-01-01

This study investigated the impact of microalgal oil (MO) on body weight management in C57BL/6J mice. Obesity was induced for 8 weeks and animals were orally supplemented with the following for 8 additional weeks: beef tallow (BT), corn oil, fish oil (FO), microalgal oil (MO), or none, as a high fat diet control group (HD). A normal control group was fed with a normal diet. After completing the experiment, the FO and MO groups showed significant decreases in body weight gain, epididymal fat pad weights, serum triglycerides, and total cholesterol levels compared to the HD and BT groups. A lower mRNA expression level of lipid anabolic gene and higher levels of lipid catabolic genes were observed in both FO and MO groups. Serum insulin and leptin concentrations were lower in the MO group. These results indicated that microalgal oil has an anti-obesity effect that can combat high fat diet-induced obesity in mice. PMID:26770909

Evaluation of safety profile of black shilajit after 91 days repeated administration in rats

PubMed Central

Velmurugan, C; Vivek, B; Wilson, E; Bharathi, T; Sundaram, T

2012-01-01

Objective To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. Methods In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2 500 and 5 000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. Results The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5 000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. Conclusions The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia. PMID:23569899

Evaluation of safety profile of black shilajit after 91 days repeated administration in rats.

PubMed

Velmurugan, C; Vivek, B; Wilson, E; Bharathi, T; Sundaram, T

2012-03-01

To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2 500 and 5 000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5 000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia.

Model-Based Normalization of a Fractional-Crystal Collimator for Small-Animal PET Imaging

PubMed Central

Li, Yusheng; Matej, Samuel; Karp, Joel S.; Metzler, Scott D.

2017-01-01

Previously, we proposed to use a coincidence collimator to achieve fractional-crystal resolution in PET imaging. We have designed and fabricated a collimator prototype for a small-animal PET scanner, A-PET. To compensate for imperfections in the fabricated collimator prototype, collimator normalization, as well as scanner normalization, is required to reconstruct quantitative and artifact-free images. In this study, we develop a normalization method for the collimator prototype based on the A-PET normalization using a uniform cylinder phantom. We performed data acquisition without the collimator for scanner normalization first, and then with the collimator from eight different rotation views for collimator normalization. After a reconstruction without correction, we extracted the cylinder parameters from which we generated expected emission sinograms. Single scatter simulation was used to generate the scattered sinograms. We used the least-squares method to generate the normalization coefficient for each LOR based on measured, expected and scattered sinograms. The scanner and collimator normalization coefficients were factorized by performing two normalizations separately. The normalization methods were also verified using experimental data acquired from A-PET with and without the collimator. In summary, we developed a model-base collimator normalization that can significantly reduce variance and produce collimator normalization with adequate statistical quality within feasible scan time. PMID:29270539

Model-Based Normalization of a Fractional-Crystal Collimator for Small-Animal PET Imaging.

PubMed

Li, Yusheng; Matej, Samuel; Karp, Joel S; Metzler, Scott D

2017-05-01

Previously, we proposed to use a coincidence collimator to achieve fractional-crystal resolution in PET imaging. We have designed and fabricated a collimator prototype for a small-animal PET scanner, A-PET. To compensate for imperfections in the fabricated collimator prototype, collimator normalization, as well as scanner normalization, is required to reconstruct quantitative and artifact-free images. In this study, we develop a normalization method for the collimator prototype based on the A-PET normalization using a uniform cylinder phantom. We performed data acquisition without the collimator for scanner normalization first, and then with the collimator from eight different rotation views for collimator normalization. After a reconstruction without correction, we extracted the cylinder parameters from which we generated expected emission sinograms. Single scatter simulation was used to generate the scattered sinograms. We used the least-squares method to generate the normalization coefficient for each LOR based on measured, expected and scattered sinograms. The scanner and collimator normalization coefficients were factorized by performing two normalizations separately. The normalization methods were also verified using experimental data acquired from A-PET with and without the collimator. In summary, we developed a model-base collimator normalization that can significantly reduce variance and produce collimator normalization with adequate statistical quality within feasible scan time.

Cerebral cortical blood flow maps are reorganized in MAOB-deficient mice

PubMed Central

Scremin, Oscar U.; Holschneider, Daniel P.; Chen, Kevin; Li, Mingen G.; Shih, Jean C.

2014-01-01

Cerebral cortical blood flow (CBF) was measured autoradiographically in conscious mice without the monoamine oxidase B (MAOB) gene (KO, n = 11) and the corresponding wild-type animals (WILD, n = 11). Subgroups of animals of each genotype received a continuous intravenous infusion over 30 min of phenylethylamine (PEA), an endogenous substrate of MAOB, (8 nmol g−1 min−1 in normal saline at a volume rate of 0.11 μl g−1 min−1) or saline at the same volume rate. Maps of relative CBF distribution showed predominance of midline motor and sensory area CBF in KO mice over WILD mice that received saline. PEA enhanced CBF in lateral frontal and piriform cortex in both KO and WILD mice. These changes may reflect a differential activation due to chronic and acute PEA elevations on motor and olfactory function, as well as on the anxiogenic effects of this amine. In addition to its effects on regional CBF distribution, PEA decreased CBF globally in KO mice (range −31% to −41% decrease from control levels) with a lesser effect in WILD mice. It is concluded that MAOB may normally regulate CBF distribution and its response to blood PEA. PMID:10095040

BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

PubMed Central

Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi, Marco Martins; Caetano, Edie Benedito

2015-01-01

Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers. PMID:27022549

Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.

PubMed

Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek

2017-02-01

The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Change in Mouse Bone Turnover in Response to Microgravity on RR-1

NASA Technical Reports Server (NTRS)

Cheng-Campbell, Margareth A.; Blaber, Elizabeth A.; Almeida, Eduardo A. C.

2016-01-01

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1ap21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23 decrease in bone fraction (p0.005) and 11.91 decrease in bone thickness (p0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n10) and vivarium controls (n10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

Changes in Mouse Bone Turnover in Response to Microgravity

NASA Technical Reports Server (NTRS)

Cheng-Campbell, M.; Blaber, E.; Almeida, E.

2016-01-01

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1a/p21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23% decrease in bone fraction (p=0.005) and 11.91% decrease in bone thickness (p=0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl/6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n=10) and vivarium controls (n=10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

Divergent outcomes of fructose consumption on exercise capacity of rats: friend or foe.

PubMed

Sun, Angela; Huang, An; Kertowidjojo, Elizabeth; Song, Su; Hintze, Thomas H; Sun, Dong

2017-02-01

To test the hypothesis that high fructose (HF) consumption divergently affects exercise capability as a function of feeding duration, rats were fed a normal (as control) diet or a normal caloric diet with HF for 3, 6, 10, and 30 days, respectively, and then were run on a treadmill. Results show that running distance and work were significantly increased, which was associated with greater exercise oxygen consumption in rats fed HF for 3 (HF-3D) and 6 days, but were decreased in rats fed HF for 30 days (HF-30D) compared with rats in their respective control groups. Shear stress-induced vasodilation (SSID) in isolated plantaris muscle arterioles was significantly greater in the HF-3D group than the control group. The difference in SSID between the two groups was abolished by N ω -nitro-l-arginine methyl ester (L-NAME), suggesting a nitric oxide (NO)-mediated response. Expression of phosphorylated/activated endothelial NO synthase (eNOS) and release of nitrite/NO were significantly increased in vessels of animals in the HF-3D group than controls. In contrast, arterioles isolated from the hypertensive rats in the HF-30D group displayed significantly attenuated NO-mediated SSID accompanied with greater production of superoxide compared with vessels of control animals. Additionally, the NO-dependent modulation of myocardial oxygen consumption (MV̇o 2 ) was also impaired in the HF-30D group, and was prevented by blocking superoxide production with apocynin, an inhibitor that also normalized the reduced SSID in the HF-30D group. In conclusion, short-term (3-6 days) HF feeding enhances exercise potential via an increase in endothelial sensitivity to shear stress, which stimulates eNOS to release NO, leading to better tissue perfusion and utilization of oxygen. However, long-term (30 days) HF feeding initiates endothelial dysfunction by superoxide-dependent mechanisms to compromise exercise performance. NEW & NOTEWORTHY The evidence that short-term fructose intake potentiates exercise capacity by nitric oxide-mediated mechanisms yields an optimal fructose feeding frame in which beneficial effects of fructose have been acquired while detrimental effects have not yet been manifested. This highlights the significance of exercise physiology in providing constructive regimens to improve physical performance. Copyright © 2017 the American Physiological Society.

Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine.

PubMed

Kim, Hubert D; Malinoski, Darren J; Borazjani, Boris; Patel, Madhukar S; Chen, Joseph; Slone, Johnathan; Nguyen, Xuan-Mai T; Steward, Earl; Schmid-Schonbein, Geert W; Hoyt, David B

2010-05-01

Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 +/- 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 +/- 1 with one early death and 2.2 +/- 1.2 with two early deaths, respectively, analysis of variance p < 0.003). The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

Diet-induced obesity reduces core body temperature across the estrous cycle and pregnancy in the rat.

PubMed

Crew, Rachael C; Waddell, Brendan J; Maloney, Shane K; Mark, Peter J

2018-04-16

Obesity during pregnancy causes adverse maternal and fetal health outcomes and programs offspring for adult-onset diseases, including cardiovascular disease. Obesity also disrupts core body temperature (T c ) regulation in nonpregnant rodents; however, it is unknown whether obesity alters normal maternal T c adaptations to pregnancy. Since T c is influenced by the circadian system, and both obesity and pregnancy alter circadian biology, it was hypothesized that obesity disrupts the normal rhythmic patterns of T c before and during gestation. Obesity was induced by cafeteria (CAF) feeding in female Wistar rats for 8 weeks prior to and during gestation, whereas control (CON) animals had free access to chow. Intraperitoneal temperature loggers measured daily T c profiles throughout the study, while maternal body composition and leptin levels were assessed near term. Daily temperature profiles were examined for rhythmic features (mesor, amplitude and acrophase) by cosine regression analysis. CAF animals exhibited increased fat mass (93%) and associated hyperleptinemia (3.2-fold increase) compared to CON animals. CAF consumption reduced the average T c (by up to 0.29°C) across the estrous cycle and most of pregnancy; however, T c for CAF and CON animals converged toward the end of gestation. Obesity reduced the amplitude of T c rhythms at estrus and proestrus and on day 8 of pregnancy, but increased the amplitude at day 20 of pregnancy. Photoperiod analysis revealed that obesity reduced T c exclusively in the light period during pre-pregnancy but only during the dark period in late gestation. In conclusion, obesity alters rhythmic T c profiles and reduces the magnitude of the T c decline late in rat gestation, which may have implications for maternal health and fetal development.

Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

PubMed

Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

2016-05-01

Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model

PubMed Central

Castillo, Gerardo M.; Nishimoto-Ashfield, Akiko; Banerjee, Aryamitra A.; Landolfi, Jennifer A.; Lyubimov, Alexander V.; Bolotin, Elijah M.

2013-01-01

Purpose Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/− PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice. Method HBEGF, PGC-HBEGF, Omeprazole, Omeprazole+PGC-HBEGF, Omeprazole+PGC-gastrin+PGC-HBEGF and epidermal growth factor (EGF)+gastrin were tested in multiple low dose streptozotocin diabetic mice. Results Omeprazole+PGC-HBEGF normalized FBG and is better than EGF+gastrin at improving islet function and decreasing insulitis. Groups treated with Omeprazole, Omeprazole+PGC-HBEGF, or EGF+gastrin have significantly improved islet function versus saline control. All animals that received PGC-HBEGF had significantly reduced islet insulitis versus saline control. Non-FBG was lower for Omeprazole+PGC-gastrin+PGC-HBEGF but Omeprazole+PGC-HBEGF alone showed better FBG and glucose tolerance. Conclusions Omeprazole+PGC-HBEGF provides a sustained exposure to both EGFRA and gastrin, improves islet function, and decreases insulitis in multiple low dose streptozotocin diabetic mice. Although HBEGF or EGF elevates non-FBG, it facilitates a reduction of insulitis and, in the presence of Omeprazole, provides normalization of FBG at the end of treatment. The study demonstrates Omeprazole and PGC-HBEGF is a viable treatment for diabetes. PMID:23793991