Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

PubMed

Avsar, M; Jansson, K; Sommer, W; Kruse, B; Thissen, S; Dreckmann, K; Knoefel, A-K; Salman, J; Hafer, C; Hecker, J; Buechler, G; Karstens, J H; Jonigk, D; Länger, F; Kaever, V; Falk, C S; Hewicker-Trautwein, M; Ungefroren, H; Haverich, A; Strüber, M; Warnecke, G

2016-05-01

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

PubMed

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

2004-12-01

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

Resolution and prevention of feline immunodeficiency virus-induced neurological deficits by treatment with the protease inhibitor TL-3.

PubMed

Huitron-Resendiz, Salvador; De Rozières, Sohela; Sanchez-Alavez, Manuel; Bühler, Bernd; Lin, Ying-Chuan; Lerner, Danica L; Henriksen, Nicholas W; Burudi, Mboya; Fox, Howard S; Torbett, Bruce E; Henriksen, Steven; Elder, John H

2004-05-01

In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. Twenty cats were divided into four groups of five animals each. Group 1 received no treatment, group 2 received TL-3 only, group 3 received FIV strain PPR (FIV-PPR) only, and group 4 received FIV-PPR and TL-3. Animals were monitored for immunological and virological status, along with measurements of brain stem auditory evoked potential (BAEP) changes. Groups 1 and 2 remained FIV negative, and groups 3 and 4 became virus positive and seroconverted by 3 to 5 weeks postinoculation. No adverse effects were noted with TL-3 only. The average peak viral load for the virus-only group 3 animals was 1.32 x 10(6) RNA copies/ml, compared to 6.9 x 10(4) copies/ml for TL-3-treated group 4 cats. Group 3 (virus-only) cats exhibited marked progressive delays in BAEPs starting at 2 weeks post virus exposure, which is typical of infection with FIV-PPR. In contrast, TL-3-treated cats of group 4 exhibited BAEPs similar to those of control and drug-only cats. At 97 days postinfection, treatments were switched; i.e., group 4 animals were taken off TL-3 and group 3 animals were treated with TL-3. BAEPs in group 3 animals returned to control levels, while BAEPs in group 4 animals remained at control levels. After 70 days on TL-3, group 3 was removed from the drug treatment regimen. Delays in BAEPs immediately increased to levels observed prior to TL-3 treatment. The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function.

Resolution and Prevention of Feline Immunodeficiency Virus-Induced Neurological Deficits by Treatment with the Protease Inhibitor TL-3

PubMed Central

Huitron-Resendiz, Salvador; de Rozières, Sohela; Sanchez-Alavez, Manuel; Bühler, Bernd; Lin, Ying-Chuan; Lerner, Danica L.; Henriksen, Nicholas W.; Burudi, Mboya; Fox, Howard S.; Torbett, Bruce E.; Henriksen, Steven; Elder, John H.

2004-01-01

In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. Twenty cats were divided into four groups of five animals each. Group 1 received no treatment, group 2 received TL-3 only, group 3 received FIV strain PPR (FIV-PPR) only, and group 4 received FIV-PPR and TL-3. Animals were monitored for immunological and virological status, along with measurements of brain stem auditory evoked potential (BAEP) changes. Groups 1 and 2 remained FIV negative, and groups 3 and 4 became virus positive and seroconverted by 3 to 5 weeks postinoculation. No adverse effects were noted with TL-3 only. The average peak viral load for the virus-only group 3 animals was 1.32 × 106 RNA copies/ml, compared to 6.9 × 104 copies/ml for TL-3-treated group 4 cats. Group 3 (virus-only) cats exhibited marked progressive delays in BAEPs starting at 2 weeks post virus exposure, which is typical of infection with FIV-PPR. In contrast, TL-3-treated cats of group 4 exhibited BAEPs similar to those of control and drug-only cats. At 97 days postinfection, treatments were switched; i.e., group 4 animals were taken off TL-3 and group 3 animals were treated with TL-3. BAEPs in group 3 animals returned to control levels, while BAEPs in group 4 animals remained at control levels. After 70 days on TL-3, group 3 was removed from the drug treatment regimen. Delays in BAEPs immediately increased to levels observed prior to TL-3 treatment. The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function. PMID:15078933

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.

Physiological Anatomical Rodent Experiment (PARE): 04 Flight Support

NASA Technical Reports Server (NTRS)

Burden, Hubert W.

1997-01-01

Rats were shipped to Kennedy Space Center (KSC), Florida, on day 2 of gestation [(G2) (day 1 = morning on which spermatozoa are present in the vagina)] and laparotomized on G7 to determine the number of implantation sites in each uterine horn. On G8, ten pregnant rats meeting flight criteria (at least five implantation sites each horn) were placed into NASA flight cages (animal enclosure modules, AEMS, five rats per cage), loaded onto the mid-deck of the space shuttle Atlantis, and on G9 (November 3, 1994) they were launched into orbit. On gestation day 20, (November 14, 1994) the shuttle returned to Edwards Air Force Base, California and the flight animals were recovered from the shuttle and subjected to unilateral hysterectomy to provide fetal material from one horn to investigators identified by NASA to study selected fetal parameters. After unilateral hysterectomy, the animals were allowed to recover and deliver vaginally. There were three groups (n = 10 each group) of control animals housed at KSC in the study. A synchronous control group, delayed 24 hours with reference to the flight group, received the same surgeries and was housed five rats per AEM and exposed to all flight conditions (identical temperatures, lighting and humidity) except microgravity. Vivarium control group I did not receive any surgery and was housed in the vivarium in clear polycarbonate cages. Vivarium control group 2 received only a unilateral hysterectomy on day 20 of gestation but otherwise was housed like the vivarium control group 1. Control groups were allowed to complete their pregnancy and deliver fetuses from the remaining horn (Synchronous control and vivarium control group 2) or horns (Vivarium control group 1). After surgery, the dams were euthanized and tissues recovered, and the neonates were assigned to foster dams.

Hippocampal place cell instability after lesions of the head direction cell network

NASA Technical Reports Server (NTRS)

Calton, Jeffrey L.; Stackman, Robert W.; Goodridge, Jeremy P.; Archey, William B.; Dudchenko, Paul A.; Taube, Jeffrey S.; Oman, C. M. (Principal Investigator)

2003-01-01

The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

Study of the protective effect of dexamethasone on cisplatin-induced ototoxicity in rats.

PubMed

Capelo, Isabelle Oliveira Jatai; Batista, Avner Marcos Alves; Brito, Yuri Neyson Ferreira; Diniz, Krissia Braga; Brito, Gerly Anne de Castro; Freitas, Marcos Rabelo de

2017-10-01

To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.

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

PubMed

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

2016-11-01

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

[Studies of bioavailability of different food sources of selenium in experiment].

PubMed

Egorova, E A; Gmoshinskiĭ, I V; Zorin, S I; Mazo, V K

2006-01-01

The selenium bioavailability in selenium enriched Spirulina (Arthrospira platensis), phycocyanin containing (Se-PC) protein isolate, separated from this micro algae and in sodium selenite was studied and compared in rats. The daily dose of selenium per one animal was 5 microgram in all experimental groups. The average selenium levels in blood serum and liver of animals that received sodium selenite during 14 days were the highest. The average selenium level in blood serum of animals fed with selenium enriched Spirulina platensis after 14 days of receiving was the same with the control group, but the average concentration of selenium in their liver was rather high and close to this parameter of sodium selenite animal group. The animals which were fed with Se-PC showed better results. Their average selenium level in blood serum was higher than in Spirulina group, but lower than in sodium selenite group. The average concentration of selenium in the liver of these animals was the same with sodium selenite animal group. As regards to animals that were fed with selenium enriched Spirulina, Se-PC and sodium selenite for 21 days, the average selenium levels ratio in their blood serum and liver was higher than in control group, but these results were not significantly different among each other. The concentrations of selenium in seminal glands in all groups of animals including control group both after 14 and 21 days feeding were close to each other.

Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

PubMed

Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

2016-08-10

There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions.

PubMed

Boyken, Janina; Frenzel, Thomas; Lohrke, Jessica; Jost, Gregor; Pietsch, Hubertus

2018-05-01

The aim of this retrospective study was to determine the gadolinium (Gd) concentration in different brain areas in a pig cohort that received repeated administration of Gd-based contrast agents (GBCAs) at standard doses over several years, comparable with a clinical setting. Brain tissue was collected from 13 Göttingen mini pigs that had received repeated intravenous injections of gadopentetate dimeglumine (Gd-DTPA; Magnevist) and/or gadobutrol (Gadovist). The animals have been included in several preclinical imaging studies since 2008 and received cumulative Gd doses ranging from 7 to 129 mmol per animal over an extended period. Two animals with no history of administration of GBCA were included as controls. Brain autopsies were performed not earlier than 8 and not later than 38 months after the last GBCA application. Tissues from multiple brain areas including cerebellar and cerebral deep nuclei, cerebellar and cerebral cortex, and pons were analyzed for Gd using inductively coupled plasma mass spectrometry. Of the 13 animals, 8 received up to 48 injections of gadobutrol and Gd-DTPA and 5 received up to 29 injections of gadobutrol only. In animals that had received both Gd-DTPA and gadobutrol, a median (interquartile range) Gd concentration of 1.0 nmol/g tissue (0.44-1.42) was measured in the cerebellar nuclei and 0.53 nmol/g (0.29-0.62) in the globus pallidus. The Gd concentration in these areas in gadobutrol-only animals was 50-fold lower with median concentrations of 0.02 nmol/g (0.01-0.02) for cerebellar nuclei and 0.01 nmol/g (0.01-0.01) for globus pallidus and was comparable with control animals with no GBCA history. Accordingly, in animals that received both GBCAs, the amount of residual Gd correlated with the administered dose of Gd-DTPA (P ≤ 0.002) but not with the total Gd dose, consisting of Gd-DTPA and gadobutrol. The Gd concentration in cortical tissue and in the pons was very low (≤0.07 nmol/g tissue) in all animals analyzed. Multiple exposure to macrocyclic gadobutrol is not associated with Gd deposition in brain tissue of healthy pigs. A single additional administration of linear Gd-DTPA is sufficient for Gd accumulation in the nucleus dentatus and globus pallidus, underlining the importance of obtaining a complete GBCA history in clinical studies.

A novel vacuum assisted closure therapy model for use with percutaneous devices.

PubMed

Cook, Saranne J; Nichols, Francesca R; Brunker, Lucille B; Bachus, Kent N

2014-06-01

Long-term maintenance of a dermal barrier around a percutaneous prosthetic device remains a common clinical problem. A technique known as Negative Pressure Wound Therapy (NPWT) uses negative pressure to facilitate healing of impaired and complex soft tissue wounds. However, the combination of using negative pressure with percutaneous prosthetic devices has not been investigated. The goal of this study was to develop a methodology to apply negative pressure to the tissues surrounding a percutaneous device in an animal model; no tissue healing outcomes are presented. Specifically, four hairless rats received percutaneous porous coated titanium devices implanted on the dorsum and were bandaged with a semi occlusive film dressing. Two of these animals received NPWT; two animals received no NPWT and served as baseline controls. Over a 28-day period, both the number of dressing changes required between the two groups as well as the pressures were monitored. Negative pressures were successfully applied to the periprosthetic tissues in a clinically relevant range with a manageable number of dressing changes. This study provides a method for establishing, maintaining, and quantifying controlled negative pressures to the tissues surrounding percutaneous devices using a small animal model. Published by Elsevier Ltd.

Effect of morphine and lacosamide on levels of dopamine and 5-HIAA in brain regions of rats with induced hypoglycemia.

PubMed

Guzman, D Calderon; Garcia, E Hernandez; Mejia, G Barragan; Olguin, H Juarez; Gonzalez, J A Saldivar; Labra Ruiz, N A

2014-01-15

The study aimed to determine the effect of morphine and lacosamide on levels of dopamine and 5-HIAA in a hypoglycemic model. Female Wistar rats (n = 30), mean weight of 180 g were treated as follow: Group 1 (control) received 0.9% NaCl, Group II; morphine (10 mg kg(-1)), Group III; lacosamide (10 mg kg(-1)), Group IV; insulin (10 U.I. per rat), Group V; morphine (10 mg kg(-1))+insulin, Group VI; lacosamide (10 mg kg(-1))+ insulin. All administrations were made intraperitoneally every 24 h, for 5 days. Animals were sacrificed after the last dose to measure the levels of glucose in blood; dopamine and 5-HIAA in cortex, hemispheres and cerebellum/medulla oblongata regions. Levels of glucose decreased significantly in animals treated with morphine, lacosamide and all groups that received insulin alone or combined with respect to control group. Levels of Dopamine diminished significantly in cortex and increased significantly in hemispheres of animals that received morphine. In cortex, 5-HIAA increase significantly in the groups treated with morphine, morphine+insulin and lacosamide+insulin, however a significant decrease of the same substance was witnessed in cerebellum and medulla oblongata of animals that received morphine or lacosamide plus insulin. GSH increased significantly in cortex and cerebellum/medulla oblongata of animals treated with morphine and lacosamide alone or combined with insulin. Lipid peroxidation decreased significantly in cortex and cerebellum/medulla oblongata of groups that received lacosamide alone or combined with insulin. These results indicate that hypoglycemia induced changes in cellular regulation while morphine and lacosamide are accompanied by biochemical responses.

Protective effect of ascorbic acid and Ginkgo biloba against learning and memory deficits caused by fluoride.

PubMed

Jetti, Raghu; Raghuveer, C V; Mallikarjuna, Rao C

2016-01-01

Fluoride is present in the ground water, World Health Organization permitted level of fluoride in the ground water is 0.5 ppm. Tooth pastes, mouth washes, tea and sea fish are the sources of fluoride. Exposure to these multiple sources results in several adverse effects in addition to the fluorosis. The present study aimed to test the effect of vitamin C and Ginkgo biloba against the behavioural deficits caused by fluoride. Rats were divided into five groups with six animals in each group (n = 6). Control group received ordinary tap water with 0.5 ppm of fluoride, the remaining groups received 100 ppm of fluoride for 30 days prior to fluoride exposure. Two groups of animals received 100 mg/kg body weight of vitamin C and G. biloba for 15 days prior to fluoride exposure. After 45 days, behavioural studies (T-Maze, passive avoidance) were conducted on the experimental animals. The results of the present study showed no behavioural deficits in the control group of animals however, the rats that received fluoride water exhibited impairment in their spatial learning and memory deficits. The deficits are not marked in the vitamin C and G. biloba groups. To conclude chronic exposure to high levels of fluoride causes severe impairment in the spatial learning and memory, these deficits can be ameliorated with the vitamin C and G. biloba. © The Author(s) 2013.

Influence of heat, wind, and humidity on ultraviolet radiation injury.

PubMed

Owens, D W; Knox, J M

1978-12-01

We investigated the influence of heat, wind, and humidity on UVR-induced acute and chronic skin damage of experimental animals housed in environmental chambers and irradiated under controlled conditions. Hairless mice (strain HRS/J) irradiated after an increase of 10 degrees F in skin temperature had more skin damage than irradiated controls. Significantly more Swiss albino mice irradiated for 400 days while maintained at 90 degrees F developed tumors than did those receiving the same amount of UVR but maintained at room temperature. Mice exposed to UVR daily for 4 weeks while kept in wind of 7 mph had greater damage and slower recovery than animals irradiated but protected from wind. Wind also accelerated tumorigenesis in mice than received chronic UVR. Mice kept at 80% relative humidity and given a single dose of UVR had greater skin injury than animals irradiated while at 5% relative humidity. High midity also appears to accelerate skin cancer formation in animals that were exposed to chronic UVR.

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

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats.

PubMed

Hernández García, Ernestina; Osnaya Brizuela, Norma; Valenzuela Peraza, Armando; Calderón Guzmán, David; Ortiz Herrera, Maribel; Juárez Olguín, Hugo; Barragán Mejía, Gerardo; Santamaría Del Ángel, Daniel; Rojas Ochoa, Alberto

2018-02-13

The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine.

Australia's continental-scale acoustic tracking database and its automated quality control process

NASA Astrophysics Data System (ADS)

Hoenner, Xavier; Huveneers, Charlie; Steckenreuter, Andre; Simpfendorfer, Colin; Tattersall, Katherine; Jaine, Fabrice; Atkins, Natalia; Babcock, Russ; Brodie, Stephanie; Burgess, Jonathan; Campbell, Hamish; Heupel, Michelle; Pasquer, Benedicte; Proctor, Roger; Taylor, Matthew D.; Udyawer, Vinay; Harcourt, Robert

2018-01-01

Our ability to predict species responses to environmental changes relies on accurate records of animal movement patterns. Continental-scale acoustic telemetry networks are increasingly being established worldwide, producing large volumes of information-rich geospatial data. During the last decade, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) established a permanent array of acoustic receivers around Australia. Simultaneously, IMOS developed a centralised national database to foster collaborative research across the user community and quantify individual behaviour across a broad range of taxa. Here we present the database and quality control procedures developed to collate 49.6 million valid detections from 1891 receiving stations. This dataset consists of detections for 3,777 tags deployed on 117 marine species, with distances travelled ranging from a few to thousands of kilometres. Connectivity between regions was only made possible by the joint contribution of IMOS infrastructure and researcher-funded receivers. This dataset constitutes a valuable resource facilitating meta-analysis of animal movement, distributions, and habitat use, and is important for relating species distribution shifts with environmental covariates.

Radio controlled release apparatus for animal data acquisition devices

DOEpatents

Stamps, James Frederick

2000-01-01

A novel apparatus for reliably and selectively releasing a data acquisition package from an animal for recovery. The data package comprises two parts: 1) an animal data acquisition device and 2) a co-located release apparatus. One embodiment, which is useful for land animals, the release apparatus includes two major components: 1) an electronics package, comprising a receiver; a decoder comparator, having at plurality of individually selectable codes; and an actuator circuit and 2) a release device, which can be a mechanical device, which acts to release the data package from the animal. To release a data package from a particular animal, a radio transmitter sends a coded signal which is decoded to determine if the code is valid for that animal data package. Having received a valid code, the release device is activated to release the data package from the animal for subsequent recovery. A second embodiment includes floatation means and is useful for releasing animal data acquisition devices attached to sea animals. This embodiment further provides for releasing a data package underwater by employing an acoustic signal.

Two-stage implant placement technique for the management of irradiated jaws: An animal study.

PubMed

Aboushelib, Moustafa N; Arnaout, Mohamed A; Elsafi, Mohamed H; Kassem, Youssef M

2017-10-01

Radiotherapy results in diminished bone remodeling capacity and an elevated risk of osteoradionecrosis, which can negatively influence the survival rate of dental implants. Patients receiving radiotherapy are advised not to receive dental implants during or soon after completing their radiotherapy. The purpose of this animal study was to investigate a 2-stage implant placement technique designed to diminish applied trauma on irradiated bone. Two groups of white New Zealand rabbits received radiotherapy in ascending doses (2, 4, 8 Gy), while a nonirradiated group served as control. Three weeks after completion of the last radiotherapy session, one of the irradiated groups and the control group received titanium dental implants bilaterally in the femur head. For the second irradiated group, an osteotomy was performed, and the surgical wound was left to heal for 2 weeks before implant placement. All animals were sacrificed 4 weeks after implant placement, and histomorphometric analysis was used to study bone-implant contact (n=14, α=.05). Statistical analysis revealed significantly higher (F=159, P<.001) bone-implant contact in the 2-stage (40.2 ±1.9) implant placement technique than in the immediately placed implants (21.2 ±2.3) in irradiated bone. Both of the groups had a significantly lower bone-to-implant contact ratio than the non-irradiated control (64.2 ±3.8). Within the limitations of this animal study, the 2-stage implant placement technique could be used to reduce trauma in irradiated bone and to improve wound healing around dental implants. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Effects of insulin-like growth factor 1 on pathologic processes in the cuprizone model of multiple sclerosis

NASA Astrophysics Data System (ADS)

Fedorishin, D.; Sorokina, I.; Tolstikova, T.; Akulov, A.; Glazacheva, V.; Nemirovich-Danchenko, N.; Khodanovich, M.; Yarnykh, V.

2017-08-01

The study aims to evaluate the effect of insulin-like growth factor 1 (IGF-1) on the demyelination and astrogliosis using the cuprizone murine model. Demyelination was induced in 14 adult male mice by 0.3% cuprizone in drinking water. Five animals from the cuprizone-treated group received subcutaneous injections of IGF-1. Seven animals were used as a control group. The extent of demyelination was evaluated as a decrease in the size of the corpus callosum on T2-weighted images that were received using an 11.7T animal MRI scanner. Brain sections were immunohistochemically stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes. It was revealed that the cuprizone caused extensive demyelination and astroglyosis. IGF-1 treatment restored the size of the corpus callosum and the number of astrocytes in the corpus callosum and the anterior commissure to the control level.

Long-term oral exposure to safe dose of bisphenol A in association with high-fat diet stimulate the prostatic lesions in a rodent model for prostate cancer.

PubMed

Facina, Camila H; Campos, Silvana G P; Gonçalves, Bianca F; Góes, Rejane M; Vilamaior, Patricia S L; Taboga, Sebastião R

2018-02-01

Studies have shown that exposure to environmental chemicals known as endocrine disruptors can cause permanent changes in genital organs, such as the prostate. Among these environmental chemicals stands out bisphenol A (BPA). Another factor associated with prostate changes is the consumption of a high-fat diet. Although the relationship between the consumption of a high-fat diet and an increased risk of prostate cancer is well established, the mechanisms that lead to the establishment of this disease are not completely understood, nor the simultaneous action of BPA and high-fat diet. Adult gerbils (100 days old) were divided in four groups (n = 6 per group): Control (C): animals that received a control diet and filtered water; Diet (D): animals that received a high-fat diet and filtered water; BPA: animals that received a control diet and BPA - 50 µg kg -1 day -1 in drinking water; BPA + Diet (BPA + D): animals that received a high-fat diet + BPA - 50 µg kg -1 day -1 in drinking water. After the experimental period (6 months), the dorsolateral and ventral prostate lobes were removed, and analyzed by several methods. Histological analysis indicated premalignant and malignant lesions in both prostatic lobes. However, animals of the D, BPA, and BPA + D groups showed a higher incidence and larger number of prostatic lesions; inflammatory foci were also common. Markers to assess prostate lesions, such as increased activation of the DNA repair system (PCNA-positive cells), androgen receptor (AR), and number of basal cells, confirmed the histology. However, serum levels of testosterone did not change under the experimental conditions. The results indicated that the methodology used was effective in generating metabolic changes, which directly compromised prostatic homeostasis. Diet and BPA appear to modulate the activation of the AR pathway and thereby optimize tumor establishment in the gerbil prostate. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

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

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.

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

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

Easterling, K.J.; Trumble, T.E.

1990-10-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively).more » Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.« less

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.

Serological response of guinea pigs to oily and aqueous inactivated vaccines containing a Brazilian isolate of the Bovine Viral Diarrhea Virus (BVDV).

PubMed

Jordão, Ricardo Spacagna; Ribeiro, Cláudia Pestana; Pituco, Edviges Maristela; Okuda, Líria Hiromi; Del Fava, Cláudia; Stefano, Eliana de; Filho, Moacir Marchiori; Mehnert, Dolores Ursula

2011-10-01

Bovine Viral Diarrhea Virus (BVDV) is widespread in cattle in Brazil and research shows its large antigenic variability. Available vaccines are produced with virus strains isolated in other countries and may not be effective. In this study, inactivated vaccines containing the Brazilian BVDV-Ib IBSP11 isolate were developed and tested on 6 groups of 10 guinea pigs (Cavia porcellus). Animals in groups A and C received an aqueous vaccine (aluminum hydroxide); B and D groups received an oily vaccine (Montanide ISA50); Group E positive-control animals were given an imported commercial vaccine with BVDV-Ia Singer; Group F animals were sham vaccinated (negative control). Groups A, B and E received two doses, and Groups C and D, three, every 21 days. Twelve blood samples were taken, at 21-day intervals over 231 days, and evaluated for antibody titer through virus-neutralization (VN), using a homologous strain (IBSP11), and a heterologous strain (BVDV-Ia NADL). Most animals, 42 days following the first dose, seroconverted to both strains and, after the second dose, there was a significant increase of titers in all groups. The oily formulation induced greater response after the third administration. This increase was not observed with the aqueous vaccines, regardless of the virus used in the VN. Antibody decline was more rapid in animals that received aqueous vaccines. The results showed the importance of studying the influence of endemic strains of commercial vaccines, to improve the efficacy of BVD vaccination. Use of the endemic strain in vaccine formulation presented promising results, as well as the use of guinea pigs as a laboratory model. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-07-01

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

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

PubMed

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

2008-04-01

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

United States Air Force Graduate Student Research Program for 1990. Program Technical Report. Volume 3

DTIC Science & Technology

1991-06-05

information would provide more precise control of the vehicle. To this extent, research has been ongoing at the Biological Acoustics Section of AAMRL... researching questions of neurobiology, particularly neurochemistry and neuroanatomy. Furthermore, I am strongly interested in the effects of ionizing and non ...administered to the animal intraperitoneally. Control animals received an injection of saline in an equivalent volume. When the colonic temperature returned to

Influence of Moxifloxacin on Hepatic Redox Status and Plasma Biomarkers of Hepatotoxicity and Nephrotoxicity in Rat

PubMed Central

Olayinka, Ebenezer Tunde

2015-01-01

Moxifloxacin is a broad spectrum fluoroquinolone antibacterial agent. We examined the hepatic redox status and plasma biomarkers of nephrotoxicity and hepatotoxicity in rat following administration of moxifloxacin (MXF). Twenty-four Wistar rats, 180–200 g, were randomized into four groups (I–IV). Animals in group I (control) received 1 mL of distilled water, while animals in groups II, III, and IV received 1 mL each of MXF equivalent to 4 mg/kg b.w., 8 mg/kg b.w., and 16 mg/kg b.w., respectively. After seven days, plasma urea, bilirubin, and creatinine were significantly (P < 0.05) elevated in the MXF-treated animals. Activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were significantly increased in the plasma of MXF-treated animals compared to control. Also plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides increased significantly in the MXF-treated groups relative to control. Moreover, MXF triggered a significant decrease in hepatic catalase, superoxide dismutase, and glutathione-S transferase activities. Likewise, MXF caused a decrease in the hepatic levels of glutathione and vitamin C. A significant increase in hepatic MDA content was also observed in the MXF-treated animals relative to control. Overall, our data suggest that the half-therapeutic, therapeutic, and twice the therapeutic dose of MXF induced nephrotoxicity, hepatotoxicity, and altered hepatic redox balance in rats. PMID:26550491

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

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

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

1994-07-01

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

Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle

NASA Technical Reports Server (NTRS)

Frank, T. C.; Dye, B. J.; Newlands, S. D.; Dickman, J. D.

1999-01-01

OBJECTIVE: The purpose of this study was to develop a technique to investigate the regeneration of utricular hair cells in the adult pigeon (Columba livia) following complete hair cell loss through administration of streptomycin. STUDY DESIGN: Experimental animal study. METHODS: Animals were divided into four groups. Group 1 received 10 to 15 days of systemic streptomycin injections. Animals in Groups 2 and 3 received a single direct placement of a 1-, 2-, 4-, or 8-mg streptomycin dose into the perilymphatic space. Animals in Groups 1 and 2 were analyzed within 1 week from injection to investigate hair cell destruction, whereas Group 3 was investigated at later dates to study hair cell recovery. Group 4 animals received a control injection of saline into the perilymphatic space. Damage and recovery were quantified by counting hair cells in isolated utricles using scanning electron microscopy. RESULTS: Although systemic injections failed to reliably achieve complete utricular hair cell destruction, a single direct placement of a 2-, 4-, or 8-mg streptomycin dose caused complete destruction within the first week. Incomplete hair cell loss was observed with the 1-mg dose. Over the long term, regeneration of the hair cells was seen with the 2-mg dose but not the 8-mg dose. Control injections of saline into the perilymphatic space caused no measurable hair cell loss. CONCLUSIONS: Direct placement of streptomycin into the perilymph is an effective, reliable method for complete destruction of utricular hair cells while preserving the regenerative potential of the neuroepithelium.

Histological evaluation of brain damage caused by crude quinolizidine alkaloid extracts from lupines.

PubMed

Bañuelos Pineda, J; Nolasco Rodríguez, G; Monteon, J A; García López, P M; Ruiz Lopez, M A; García Estrada, J

2005-10-01

The effects of the intracerebroventricular (ICV) administration of crude extracts of lupin quinolizidine alkaloids (LQAs) were studied in adult rat brain tissue. Mature L. exaltatus and L. montanus seeds were collected in western Mexico, and the LQAs from these seeds were extracted and analyzed by capillary gas chromatography. This LQA extract was administered to the right lateral ventricle of adult rats through a stainless steel cannula on five consecutive days. While control animals received 10 microl of sesame oil daily (vehicle), the experimental rats (10 per group) received 20 ng of LQA from either L. exaltatus or from L. montanus. All the animals were sacrificed 40 h after receiving the last dose of alkaloids, and their brains were removed, fixed and coronal paraffin sections were stained with haematoxylin and eosin. Immediately after the administration of LQA the animals began grooming and suffered tachycardia, tachypnea, piloerection, tail erection, muscular contractions, loss of equilibrium, excitation, and unsteady walk. In the brains of the animals treated with LQA damaged neurons were identified. The most frequent abnormalities observed in this brain tissue were "red neurons" with shrunken eosinophilic cytoplasm, strongly stained pyknotic nuclei, neuronal swelling, spongiform neuropil, "ghost cells" (hypochromasia), and abundant neuronophagic figures in numerous brain areas. While some alterations in neurons were observed in control tissues, unlike those found in the animals treated with LQA these were not significant. Thus, the histopathological changes observed can be principally attributed to the administration of sparteine and lupanine present in the alkaloid extracts.

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.

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice.

PubMed

Rojas-Ortiz, Yoel Antonio; Rundle-González, Valerie; Rivera-Ramos, Isamar; Jorge, Juan Carlos

2006-01-01

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.

Development of an animal model of fibrous cholangitis in pigs.

PubMed

Lainakis, Nektarios G; Papalois, Apostolos; Agrogiannis, Georgios; Antonopoulos, Constantine N; Michail, Panagiotis; Bastounis, Elias; Patsouris, Efstathios; Felekouras, Evangelos

2014-04-01

The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0-5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Statistically significant differences were observed for most of the histopathological markers between the group of pigs' offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

Supplementation with dry Mimosa caesalpiniifolia leaves can reduce the Haemonchus contortus worm burden of goats.

PubMed

Brito, D R B; Costa-Júnior, L M; Garcia, J L; Torres-Acosta, J F J; Louvandini, H; Cutrim-Júnior, J A A; Araújo, J F M; Soares, E D S

2018-03-15

Gastrointestinal nematodes (GINs) cause considerable economic losses in grazing goat herds. At present, GIN control cannot rely on conventional anthelmintic (AH) drugs because parasites have developed resistance against such drugs. Thus, alternative control methods are being sought to reduce the dependence on AH. Many tannin-rich plants exhibit AH activity and may be used as alternatives for GIN control. Mimosa caesalpiniifolia is a tannin-rich shrub consumed by small ruminants in Brazil. This study evaluated the in vivo AH effect of M. caesalpiniifolia leaf powder supplementation on GIN egg fecal excretion and worm burden in goats. Plant leaves were harvested, dried and ground to obtain a powder. Twenty-four castrated male goats, aged six to eight months, with a mean body weight of 15.0 ± 2.5 kg were used in the experiment. Animals were infected orally with 16,000 larvae comprising 50% Haemonchus spp., 41% Trichostrongylus spp. and 9% Oesophagostomum spp. Once the infection was patent, the goats were distributed into four groups of six animals. The control group received concentrate without condensed tannins (CTs) and did not receive any drench against GINs. The monepantel group received concentrate without CTs and were drenched once with monepantel. The other two groups received the M. caesalpiniifolia leaf powder in two periods of seven consecutive days (days 1-7 and 14-21), with one of the groups also receiving 10 g of polyethyleneglycol (PEG)/day. The animals were weighed weekly, and individual fecal eggs counts (FECs) were performed daily. After 28 days, the animals were humanly slaughtered, and the worm burden was estimated. Although live weight gain and FECs did not differ among the groups (P > 0.05), post-mortem worm counts showed a reduction in Haemonchus contortus adult worm burden (57.7%) in goats of the CT group compared to control goats (P < 0.05). The addition of PEG did not diminish AH activity in the CT + PEG group (66.9% reduction compared to the control). No AH effect against other GIN species was found. The result for the addition of PEG suggested that the observed AH activity was associated with plant secondary compounds, as opposed to CTs. As expected, no AH effect against Oesophagostomum columbianum was found for the monepantel group showed. Thus, feeding dry leaves of M. caesalpiniifolia represent a promising alternative for the control of GIN infections in goats. Copyright © 2018 Elsevier B.V. All rights reserved.

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.

PubMed

Lee, Jung-Seok; Wikesjö, Ulf M E; Jung, Ui-Won; Choi, Seong-Ho; Pippig, Susanne; Siedler, Michael; Kim, Chong-Kwan

2010-04-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model. Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow. rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.

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.

Coadministration of nematophagous fungi for biological control over gastrointestinal helminths in sheep in the semiarid region of northeastern Brazil.

PubMed

Vilela, Vinícius Longo Ribeiro; Feitosa, Thais Ferreira; Braga, Fabio Ribeiro; Araújo, Jackson Victor de; Santos, Antonielson dos; Morais, Dayana Firmino de; Souto, Diego Vagner de Oliveira; Athayde, Ana Célia Rodrigues

2016-05-15

This study aimed to evaluate coadministration of Duddingtonia flagrans and Monacrosporium thaumasium in a sodium alginate matrix for controlling gastrointestinal helminths in young and adult sheep in the semiarid region of northeastern Brazil. An area of 1ha was divided into two paddocks, in which two experimental groups (fungus and control) were formed, each consisting of six adult females and ten young males. In each group, two subgroups were formed in accordance with the animal category (adult or young). In the fungus group, each animal received 3g of pellets containing 0.6g of fungal mycelium, with 0.3g of D. flagrans and 0.3g of M. thaumasium for each 10 kg of body weight, in their feed twice a week, for six months. In the control group, each animal received 3g of pellets without fungus for each 10 kg of body weight, in their feed twice a week, for six months, serving as a witness group. Reductions in numbers of eggs per gram of feces of 76% among the adult sheep in the fungus group and 83% among the young sheep in the fungus group were observed, in comparison with their respective control subgroups. The groups that received these fungi needed less salvage deworming and presented better packed cell volume percentages, better weight gain and lower levels of L3/kg dry matter in their paddock than the control groups. Thus, it was concluded that coadministration of D. flagrans and M. thaumasium was effective in controlling gastrointestinal helminths of adults and young sheep in the semiarid region of northeastern Brazil. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

PubMed Central

Bateman, Emma; Bowen, Joanne; Stringer, Andrea; Mayo, Bronwen; Plews, Erin; Wignall, Anthony; Greenberg, Norman; Schiffrin, Eduardo; Keefe, Dorothy

2013-01-01

Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis. PMID:24084053

Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study.

PubMed

Arikan, Gul; Karatas, Ezgi; Lebe, Banu; Ayhan, Ziya; Utine, Canan Asli; Kutsoylu, Oya Eren; Gunenc, Uzeyir; Yilmaz, Osman

2018-04-26

To identify the risk of inducing ocular surface dysplasia following topical administration of 1% voriconazole eye drop. Fourteen noninflamed healthy eyes of 14 white adult New Zealand rabbits were included in the study. The rabbits were randomly divided into two groups comprised of 7 rabbits each. Group 1 received topical 1% voriconazole and Group 2 received topical saline as the control group. In all animals, right eye was selected for the study. In Group 1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single drop of saline was instilled every 10 min consecutively for 17 times a day for 60 days. At two months, animals were sacrificed and study eyes were enucleated with the eyelids. The specimens were stained with hematoxylin-eosin and histopathologic changes in cornea, bulbar and palpebral conjunctiva were evaluated under light microscope. There were no macroscopically visible lesions on the ocular surface of any rabbits. Histopathological evaluation showed mild to moderate dysplasia localized mainly in the limbus and extending to the adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group. Severe dysplasia or carcinoma in situ was not observed. In the Control Group, dysplasia was not observed, at all. This animal study provides a possible relationship between topically administered 1% voriconazole and ocular surface dysplasia. We recommend ophthalmologists to be aware of the risk of ocular surface dysplasia in patients received voriconazole eye drop.

Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption.

PubMed

Nardi, Jessica; Moras, Patricia Bonamigo; Koeppe, Carina; Dallegrave, Eliane; Leal, Mirna Bainy; Rossato-Grando, Luciana Grazziotin

2017-02-01

Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of an energy block containing Duddingtonia flagrans in the control of gastrointestinal nematodes of sheep.

PubMed

Sagüés, María F; Fusé, Luis A; Fernández, Alicia S; Iglesias, Lucía E; Moreno, Fabiana C; Saumell, Carlos A

2011-09-01

The efficacy of the nematode-trapping fungus Duddingtonia flagrans incorporated into an energy block was evaluated for the control of gastrointestinal nematodes in sheep. Four naturally parasitised sheep with average nematode egg counts of 2,470 eggs per gram grazed by pairs on two similar parasite-free paddocks for 30 days. During that period, one pair of sheep (treated animals, T1) received an energy block containing chlamydospores of D. flagrans at a dose of 200,000 chlamydopores/kg bw/day, while the second pair (control animals, C1) received a fungus-free energy block. The animals in both groups were taken off the paddocks after contaminating the pastures for a month with either nematode eggs plus fungal chlamydospores (T1) or nematode eggs alone (C1). Twelve parasite-free sheep were divided into two groups of six animals each, the treated group (T2) was placed on the paddock previously contaminated with parasites and fungus, while the control group (C2) was placed on the parasite-only paddock. These two groups grazed on their respective paddocks during 30 days and were then housed for 15 days, after which period they were slaughtered in order to determine the parasite burden present in each animal. Results showed that animals in group T2 harboured significantly less nematodes than their counterpart in group C2. The efficacy of D. flagrans was 92% against the total parasite burden, 100% against Haemonchus contortus and Teladorsagia circumcincta, 89.9% against Trichostrongylus colubriformis, 87.5% against Cooperia onchopora, and 90% against Trichostrongylus axei. No efficacy was detected against Nematodirus spathiger, Trichuris ovis and T. skrjabini.

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.

Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

USDA-ARS?s Scientific Manuscript database

The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

76 FR 62451 - Manufacturer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances..., made application by renewal to the Drug Enforcement Administration (DEA) to be registered as a bulk... for other animal and wildlife applications. No comments or objections have been received. DEA has...

Effect of intraosseous anesthesia on control of hemostasis in pigs.

PubMed

Baker, Tyler F; Torabinejad, Mahmoud; Schwartz, Stephen F; Wolf, David

2009-11-01

Intraosseous anesthesia is used to deliver anesthetic into cancellous bone adjacent to the root apices. No study has assessed the effect of this anesthetic technique on hemostasis. The purpose of this study was to compare the amount of bleeding from soft tissue and bone in pig jaws after preoperative intraosseous or infiltration anesthesia with 2% lidocaine containing 1:50,000 epinephrine. Twelve pigs were divided into 3 groups. The first group received infiltration anesthesia on one half of the jaw and no anesthesia on the other half. The second group received intraosseous anesthesia on one half of the jaw and no anesthesia on the other half. The third group received infiltration anesthesia on one half of the jaw and intraosseous anesthesia on the second half. Blood was collected during flap reflection to measure the volume of soft tissue bleeding. Osteotomies were then prepared with blood collected from the surgical site to measure the volume of osseous bleeding. The median soft tissue blood loss observed in animals receiving infiltration anesthesia (1.14 mL) was significantly less as compared with animals that received no anesthesia (4.49 mL) or intraosseous anesthesia (2.45 mL). Compared with median hard tissue blood loss observed in animals without anesthesia (1.51 mL), significantly less blood loss was observed in animals receiving either infiltration anesthesia (0.67 mL) or intraosseous anesthesia (0.76 mL). Infiltration anesthesia resulted in significantly less soft tissue bleeding (p = .004) as compared with no anesthesia. Infiltration and intraosseous anesthesia resulted in significantly less osseous bleeding than the use of no anesthetic (p < .001). The volume of blood loss for each animal was shown to be below the maximum safe volume of blood loss for a single procedure.

Effect of an electronic control device exposure on a methamphetamine-intoxicated animal model.

PubMed

Dawes, Donald M; Ho, Jeffrey D; Cole, Jon B; Reardon, Robert F; Lundin, Erik J; Terwey, Karen S; Falvey, Dan G; Miner, James R

2010-04-01

Because of the prevalence of methamphetamine abuse worldwide, it is not uncommon for subjects in law enforcement encounters to be methamphetamine-intoxicated. Methamphetamine has been present in arrest-related death cases in which an electronic control device (ECD) was used. The primary purpose of this study was to determine the cardiac effects of an ECD in a methamphetamine intoxication model. Sixteen anesthetized Dorset sheep (26-78 kg) received 0.0 mg/kg (control animals, n = 4), 0.5 mg/kg (n = 4), 1.0 mg/kg (n = 4), or 1.5 mg/kg (n = 4) of methamphetamine hydrochloride as a slow intravenous (IV) bolus during continuous cardiac monitoring. The animals received the following exposures in sequence from a TASER X26 ECD beginning at 30 minutes after the administration of the drug: 1) 5-second continuous exposure, 2) 15-second intermittent exposure, 3) 30-second intermittent exposure, and 4) 40-second intermittent exposure. Darts were inserted at the sternal notch and the cardiac apex, to a depth of 9 mm. Cardiac motion was determined by thoracotomy (smaller animals, < or = 32 kg) or echocardiography (larger animals, > 68 kg). Data were analyzed using descriptive statistics and chi-square tests. Animals given methamphetamine demonstrated signs of methamphetamine toxicity with tachycardia, hypertension, and atrial and ventricular ectopy in the 30-minute period immediately after administration of the drug. Smaller animals (n = 8, < or = 32 kg, mean = 29.4 kg) had supraventricular dysrhythmias immediately after the ECD exposures. Larger animals (n = 8, > 68 kg, mean = 72.4) had only sinus tachycardia after the exposures. One of the smaller animals had frequent episodes of ventricular ectopy after two exposures, including runs of delayed onset, nonsustained six- to eight-beat unifocal and multifocal ventricular tachycardia that spontaneously resolved. This animal had significant ectopy prior to the exposures as well. Thoracotomy performed on three smaller animals demonstrated cardiac capture during ECD exposure consistent with previous animal studies. In the larger animals, none of the methamphetamine-intoxicated animals demonstrated cardiac capture. Two control sheep showed evidence of capture similar to the smaller animals. No ventricular fibrillation occurred after the exposure in any animal. In smaller animals (32 kg or less), ECD exposure exacerbated atrial and ventricular irritability induced by methamphetamine intoxication, but this effect was not seen in larger, adult-sized animals. There were no episodes of ventricular fibrillation after exposure associated with ECD exposure in methamphetamine-intoxicated sheep.

[The diet, fortified with fluorine and its influence on strontium accumulation in bone tissue of animals].

PubMed

Dubtsov, G G; Novikova, Zh V; Komleva, V A

2007-01-01

The research work was devoted to accumulation of strontium-90 (Sr-90) in bone tissue of animals (white rats) and its dependence on the diet, enriched with Fluorine (F). Totally each rat received 18,5 MBk of strontium-90. Insertion of rusks, fortified with sodium fluoride to the rats dietary intake, reduces accumulation of strontium-90 in bone tissue for 26% comparatively to control group of animals. Stimulation action of fluorine on hematopoietic function of irradiated animals were also determined.

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

PubMed

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

2010-04-19

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

Telencephalic neural activation following passive avoidance learning in a terrestrial toad.

PubMed

Puddington, Martín M; Daneri, M Florencia; Papini, Mauricio R; Muzio, Rubén N

2016-12-15

The present study explores passive avoidance learning and its neural basis in toads (Rhinella arenarum). In Experiment 1, two groups of toads learned to move from a lighted compartment into a dark compartment. After responding, animals in the experimental condition were exposed to an 800-mM strongly hypertonic NaCl solution that leads to weight loss. Control animals received exposure to a 300-mM slightly hypertonic NaCl solution that leads to neither weight gain nor loss. After 10 daily acquisition trials, animals in the experimental group showed significantly longer latency to enter the dark compartment. Additionally, 10 daily trials in which both groups received the 300-mM NaCl solution after responding eliminated this group effect. Thus, experimental animals showed gradual acquisition and extinction of a passive avoidance respond. Experiment 2 replicated the gradual acquisition effect, but, after the last trial, animals were sacrificed and neural activation was assessed in five brain regions using AgNOR staining for nucleoli-an index of brain activity. Higher activation in the experimental animals, relative to controls, was observed in the amygdala and striatum. Group differences in two other regions, lateral pallium and septum, were borderline, but nonsignificant, whereas group differences in the medial pallium were nonsignificant. These preliminary results suggest that a striatal-amygdala activation could be a key component of the brain circuit controlling passive avoidance learning in amphibians. The results are discussed in relation to the results of analogous experiments with other vertebrates. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Transmission of Sarcoptes scabiei from animal to man and its control.

PubMed

Mitra, M; Mahanta, S K; Sen, S; Ghosh, C; Hati, A K

1995-04-01

Outbreak of Sarcoptes scabiei in animals spilling over to man in close association was observed in two adjacent villages, Fewgram and Nurpur in the district of Birbhum, West Bengal, from mid-November to mid-December, 1991. Nineteen goats and one calf who did not receive any treatment died of sarcoptic manage. All infected animals got cured with external application of deltamethrin, a synthetic pyrethroid and triazapentadiene. Human cases were treated successfully with benzene hexachloride (2%).

75 FR 69467 - Manufacturer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances... 80524, made application by renewal to the Drug Enforcement Administration (DEA) to be registered as a..., zoos, and for other animal and wildlife applications. No comments or objections have been received. DEA...

Biological control of cyathostomin (Nematoda: Cyathostominae) with nematophagous fungus Monacrosporium thaumasium in tropical southeastern Brazil.

PubMed

Tavela, Alexandre de Oliveira; Araújo, Jackson Victor; Braga, Fábio Ribeiro; Silva, André Ricardo; Carvalho, Rogério Oliva; Araujo, Juliana Milani; Ferreira, Sebastião Rodrigo; Carvalho, Giovanni Ribeiro

2011-01-10

Horses are hosts to a wide variety of helminthes; the most important are the cyathostomin, or small strongyles. The viability of a fungal formulation (pellets) using the nematode-trapping fungus Monacrosporium thaumasium was assessed in biological control of horse cyathostomin. Two groups (fungus-treated and control) consisted of six mares in each group, crossbred (ages of 2.5 and 3.5 years), were placed in pastures of Cynodon sp. naturally infected with horse cyathostomin larvae. In the treated group, each animal received 1g/10 kg body weight (0.2g/10 kg live weight of fungus) of pellets of sodium alginate matrix containing the fungus M. thaumasium orally, twice a week for 6 months. In the control group, animals received (1g/10 kg body weight) of pellets without fungus. The egg count per gram of feces showed difference (p<0.01) in the animals treated with the fungus in relation to the control animals during all months of the experiment. The EPG percentage decrease were 87.5%, 89.7%, 68.3%, 58.7%, 52.5% and 35.2% during June, July, August, September, October and November, respectively. In faecal cultures, there was difference (p<0.05) among animals treated with fungus was found in relation to the control animals during all the experiment month, with percentage reduction of 67.5%, 61.4% and 31.8% in September, October and November, respectively. Difference (p<0.01) was observed in the recovery of infective larvae from pastures that were collected up to 20 cm from the dung pats in pastures in the group treated with the fungus in relation to the control group with a reduction of 60.9% and between 0-20 and 0-40 cm from the faecal pat reduction (p<0.01) was about 56% in the group treated with the fungus M. thaumasium in relation to the control group pasture. There was no difference (p>0.05) between the average weight gains in both animal groups. The treatment of horses with pellets containing the nematophagous fungus M. thaumasium can be effective in controlling cyathostomin in the tropical region of southeastern Brazil. Copyright © 2010 Elsevier B.V. All rights reserved.

Neuromuscular stimulation therapy after incomplete spinal cord injury promotes recovery of interlimb coordination during locomotion

NASA Astrophysics Data System (ADS)

Jung, R.; Belanger, A.; Kanchiku, T.; Fairchild, M.; Abbas, J. J.

2009-10-01

The mechanisms underlying the effects of neuromuscular electrical stimulation (NMES) induced repetitive limb movement therapy after incomplete spinal cord injury (iSCI) are unknown. This study establishes the capability of using therapeutic NMES in rodents with iSCI and evaluates its ability to promote recovery of interlimb control during locomotion. Ten adult female Long Evans rats received thoracic spinal contusion injuries (T9; 156 ± 9.52 Kdyne). 7 days post-recovery, 6/10 animals received NMES therapy for 15 min/day for 5 days, via electrodes implanted bilaterally into hip flexors and extensors. Six intact animals served as controls. Motor function was evaluated using the BBB locomotor scale for the first 6 days and on 14th day post-injury. 3D kinematic analysis of treadmill walking was performed on day 14 post-injury. Rodents receiving NMES therapy exhibited improved interlimb coordination in control of the hip joint, which was the specific NMES target. Symmetry indices improved significantly in the therapy group. Additionally, injured rodents receiving therapy more consistently displayed a high percentage of 1:1 coordinated steps, and more consistently achieved proper hindlimb touchdown timing. These results suggest that NMES techniques could provide an effective therapeutic tool for neuromotor treatment following iSCI.

An imported case of canine rabies in Aquitaine: Investigation and management of the contacts at risk, August 2004-March 2005.

PubMed

Servas, V; Mailles, A; Neau, D; Castor, C; Manetti, A; Fouquet, E; Ragnaud, J M; Bourhy, H; Paty, M C; Melik, N; Astoul, J; Cliquet, F; Moiton, M P; François, C; Coustillas, M; Minet, J-C; Parriaud, P; Capek, I; Filleul, L

2005-11-01

In August 2004, a case of rabies was diagnosed in a puppy that had been illegally imported from Morocco to Bordeaux (France). Because a great number of people and animals were thought to have come into contact with the puppy, extensive tracing measures were implemented, and an international alert was launched to trace and treat the contacts at risk. One hundred and eighty seven people received post-exposure treatment, eight of whom also received serovaccination, and 57 animals known to have been exposed to the puppy were tested. Six months after the death of the rabid animal, none of the people treated showed any signs of rabies, nor was any secondary animal case reported. The management of this crisis highlights the importance of the role of a rapid alert system at European level. Strict application of sanitary control regulations is essential for animals introduced into EU countries, and all necessary information must be made available to EU residents travelling to rabies enzootic areas.

Further evidence supporting the concurrent influence of aflatoxin and manganese

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

Katzen, J.S.; Llewellyn, G.C.

Trace elements, including manganese may afford protection from deleterious effects of aflatoxin. Young male Fischer rats received ip injections of aflatoxin B1 (AFB1) in dimethyl sulfoxide (DMSO), 1 mg/kg, 2 mg/kg or 4 mg/kg. Control groups received DMSO ip or no injection. All animals were intubated with 3 microCi of (/sup 54/Mn)-MnCl/sub 2/ 12 hr post-injection. Sacrifice occurred 72 hr after gavage of the radiolabel. All tested levels of AFB1 affected the loss of total body radioactivity. This response was observed within 12 hr when toxin-treated groups excreted almost 4 times more counts than controls. From 12-36 hr following radiolabelmore » administration, AFB1 appeared to enhance excretion; by 72 hr, toxin-treated animals (especially those receiving higher doses) appeared to conserve the metal. Aflatoxicosis manifested itself through reduced body weight gain. The data provide support evidence that Mn and AFB1 biointeract.« less

THE ABSCOPAL EFFECT OF X IRRADIATION ON BONE GROWTH IN RATS

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

Pappas, A.M.; Cohen, J.

1963-06-01

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

Fennel induces cytotoxic effects against testicular germ cells in mice; evidences for suppressed pre-implantation embryo development.

PubMed

Minas, Aram; Najafi, Gholamreza; Jalali, Ali Shalizar; Razi, Mazdak

2018-05-15

Foeniculum vulgare (FVE; fennel) is an aromatic plant belonging to Umbelliferae family, which is widely used in traditional societies because of its different pharmaceutical properties. To uncover the fennel-derived essential oil (FVEO)-induced effects on male reproductive potential, 24 mature male albino mice were divided into, control, 0.37, 0.75, and 1.5 mg kg -1 FVEO-received groups. Following 35 days, the animals were euthanized and the testicular tissue and sperm samples were collected. The histological alterations, tubular differentiation (TDI), spermiogenesis (SPI) indices, apoptosis ratio, and RNA damage of germinal cells were analyzed. Moreover, the sperm count, motility, viability, chromatin condensation, and DNA fragmentation were assessed. Finally, the pre-implantation embryo development including; the percentage of zygote, 2-cell embryos and blastocysts were assessed. Observations showed that the FVEO, dose dependently, increased histological damages, resulted in germ cells dissociation, depletion, nuclear shrinkage and significantly (P < .05) decreased tubular differentiation and spermiogenesis ratios. Moreover, the FVEO-received animals (more significantly in 1.5 mg kg -1 -received group) exhibited decreased sperm count, viability, and motility and represented enhanced percentage of sperms with decondensed chromatin and DNA fragmentation. Finally, the animals in FVEO-received group showed diminished zygote formation and represented decreased pre-implantation embryo development compared to control animals. In conclusion, our data showed that, FVEO albeit at higher doses, is able to adversely affect cellular DNA and RNA contents, which in turn is able to negatively affect the sperm count and morphology. All these impairments are able to negatively affect the fertilization potential as well as pre-implantation embryo development. © 2018 Wiley Periodicals, Inc.

Evaluation of in-feed larch sawdust anti-inflammatory effect in sows.

PubMed

Tzika, E D; Tassis, P D; Papatsiros, V G; Pferschy-Wenzig, E M; Siochu, A; Bauer, R; Alexopoulos, C; Kyriakis, S C; Franz, C

2017-03-01

The study aimed to investigate the possible anti-inflammatory activity of larch sawdust as feed supplement in lactating sows' diet and its possible effect on the prevalence of Postpartum Dysgalactia Syndrome under field conditions. In a Greek farrow-to-finish pig farm, fifteen sows were randomly and equally allocated to a negative control group (NC group), a positive control group (PC group), and a treatment group (LT group). The animals of the first two groups received 99% basic diet and 1% corn starch, while LT group animals received 99% basic diet and 1% larch sawdust. The whole trial period lasted 35 days (7 days prior to farrow - day of weaning). At parturition day, animals of the PC group received 2 ml of an anti-inflammatory drug intramuscularly (meloxicam, Metacam®, Boehringer Ingelheim Vetmedica), while the animals of both other groups, received 2 ml of normal saline. Results showed insignificant differences among experimental groups for parameters such as post-partum rectal temperature and piglets performance. On the contrary, a significant increase of mean milk lactation index was observed in LT and PC groups on the 4th day of lactation period, when compared with NC group (p=0.014). Additionally, mean IL-6 concentrations in blood in the LT group showed a tendency for reduction when compared with those found in NC, and insignificant difference (p>0.05) when compared with those observed in PC group 24 hours postpartum. Moreover, the respective TNFα mean level in the LT group at 24 and 72 hours after parturition was similar to that found in PC group, respectively) and significantly lower than that determined in the NC group (p=0.003, p=0.024. The results suggest a possible anti-inflammatory effect of larch sawdust in sows.

Manipulation of reproductive performance of lactating buffaloes using melatonin and controlled internal drug release device treatment during out-of-breeding season under tropical conditions.

PubMed

Ramadan, T A; Sharma, R K; Phulia, S K; Balhara, A K; Ghuman, S S; Singh, I

2016-09-01

Twelve lactating Murrah buffalo, divided into control and treatment group of six animals each, were used to study the effect of melatonin and controlled internal drug release (CIDR) device treatment on the resumption of ovarian activity during out-of-breeding season (summer solstice). Treated group implanted with melatonin (18-mg melatonin/50-kg body weight) for 45 days and then animals of both groups received CIDR for 9 days. All animals received intramuscular 500 IU eCG, at day before CIDR removal, and 10-μg GnRH at day after CIDR withdrawal. All animals were subjected to estrus detection daily. Blood samples in conjunction with transrectal ultrasonography were performed once a week to determine serum concentrations of melatonin, progesterone, and antioxidant enzyme activities, as well as to monitor the ovarian activity. Melatonin treatment resulted in an increase (P < 0.01) in the overall mean superoxide dismutase activity. Melatonin and CIDR increased the diameter of CL (P < 0.01) and plasma progesterone concentration (P < 0.05). In addition, melatonin and CIDR exhibited superior ability to maintain presence of CL at Day 21 and Day 30 after artificial insemination and achieved higher percentage of conception rate than control. In conclusion, the CIDR treatment preceded by melatonin improved the reproductive performance in lactating buffaloes during out-of-breeding season under tropical conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Supplementation with plant extracts (carvacrol, cinnamaldehyde and capsaicin): its effects on acid-base status and productive performance in growing/finishing bull calves.

PubMed

Hernández, Joaquín; Benedito, José Luís; Vázquez, Patricia; Pereira, Victor; Méndez, Jesús; Sotillo, Juan; Castillo, Cristina

2009-01-01

This study investigated the in vivo effects of a commercial blend of plant extracts (carvacrol, cinnamaldehyde and capsaicin) on blood acid-base balance and serum lactate levels in a 148-day feedlot experimentwith 24 double-muscled Belgian Blue bull calves. Animals were allotted randomly to one of two experimental groups: 1) a control group (C, no supplementation; n = 10), and 2) a group receiving dietary supplementation with a combination of plant extracts (PE, 100 mg per kg DM of concentrate; n = 14). All animals received a high-grain ration, typical of diets fed commercially to feedlot cattle in Spain, consisting mainly of barley plus other components in proportions depending on the production phase. Production data (weight, DMI, ADG and feed-to-gain ratio) were recorded, and venous blood pH, pCO2, HCO3(-), Base Excess -BE- and serum L-lactate were determined. Apparently, beneficial effects of supplementation on production parameters were observed in both growing and finishing periods, though statistically significant effects were only observed in the finishing period. As regards blood parameters, no significant effects of supplementation (or the supplementation x time interaction) were observed, except for an effect on blood pH in the growing period, when supplemented animals showed significantly higher values than controls. A beneficial supplementation x time interactive effect was observed on serum L-lactate levels: from the first week of the study until the end, supplemented animals showed significantly lower levels than controls. These in vivo results support the utility of this dietary supplement in feedlot cattle receiving a barley-based high-grain diet.

TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo.

PubMed

Arpornchayanon, Warangkana; Canis, Martin; Ihler, Friedrich; Settevendemie, Claudia; Strieth, Sebastian

2013-08-01

Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-α inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Guinea pigs (n = 6, per group). Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-α inhibitor in contrast to a significant threshold raising in controls. TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.

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

PubMed

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

2009-01-01

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

Allium sativum (garlic) treatment for murine transitional cell carcinoma.

PubMed

Riggs, D R; DeHaven, J I; Lamm, D L

1997-05-15

Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.

Effects of topical oxiconazole and boric acid in alcohol solutions to rat inner ears.

PubMed

Özdemir, Süleyman; Tuncer, Ülkü; Tarkan, Özgür; Akar, Funda; Sürmelioğlu, Özgür

2013-06-01

The aim of this study is to evaluate the ototoxicity of topical oxiconazole and boric acid in alcohol solutions. Prospective controlled animal study. Research laboratory. Fifty adult Wistar albino rats were divided into 5 groups consisting of 10 animals each. The right tympanic membranes were perforated, and baseline and posttreatment distortion product otoacoustic emission (DPOAE) measurements were performed. The solutions were applied through the external ear canal to the middle ear twice a day for 14 days. The rats in group I and group II received 0.1 mL of oxiconazole-containing solution drops and 4% boric acid in alcohol solution drops, respectively. Group III received gentamicin solution (40 mg/mL) (ototoxic control), group IV received saline solution, and group V was followed without any medication. The baseline DPOAE results of the right ears of all animals tested were normal. Animals in groups I, II, IV, and V showed no statistically significant change in the DPOAE amplitudes. The rats in the gentamicin group showed a significant decrease. This study demonstrates that topically used oxiconazole and boric acid in alcohol solutions to the middle ear appear to be safe on the inner ear of rats. The safety of these drugs has not yet been confirmed in humans. Caution should be taken when prescribing these drugs, especially to patients who had tympanic membrane perforation. Ear drops should be chosen more carefully in an external ear infection for patients with tympanic membrane perforation to avoid ototoxicity.

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task.

PubMed

Haddon, J E; Killcross, S

2011-12-29

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was "over-trained" relative to the other, "under-trained," discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Preliminary study of the effects of smectite granules (WoundStat) on vascular repair and wound healing in a swine survival model.

PubMed

Gerlach, Travis; Grayson, J Kevin; Pichakron, Kullada O; Sena, Matthew J; DeMartini, Steven D; Clark, Beth Z; Estep, J Scot; Zierold, Dustin

2010-11-01

WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

The Effects of Collaborative Care of Living Animals in Biology Lessons on Students' Relatedness Toward Their Teacher Across Gender

NASA Astrophysics Data System (ADS)

Eckes, Alexander; Großmann, Nadine; Wilde, Matthias

2018-01-01

The transition from elementary school to the upper grades can lead to ambiguous feelings toward the new, male teachers. This study investigated whether collaborative animal care in biology lessons affects students' feelings of relatedness toward their biology teachers positively during the first year after the school transition. Four hundred twenty fifth graders (M age = 10.5 years, SD age = 0.6 years) of higher types of tracking participated. We designed one experimental group that involved caring for the living animals to be used in the upcoming lessons, and two control groups. The first control group included lessons with living animals, but did not include prior care of those animals, and the second incorporated neither living animals nor prior care. All groups received biology lessons with the same content. To examine the effects of caretaking, we used an adapted version of the scale "relatedness" (Ryan 1982). In both control groups, boys showed lower relatedness toward female teachers and girls toward male teachers, respectively. Collaborative mice care promoted equal relatedness across all gender combinations among teachers and students.

Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

PubMed

Abdul-Hamid, Manal; Gallaly, Sanaa Rida

2014-05-01

The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

[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.

Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation.

PubMed

Dorfman, Tatiana; Pollak, Yulia; Sohotnik, Rima; Coran, Arnold G; Bejar, Jacob; Sukhotnik, Igor

2015-09-01

The Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/β-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic-insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily. Rats were killed on day 7. Wnt/β-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in β-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/β-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation. © 2015 Society for Endocrinology.

The effects of repeated low-dose sarin exposure

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

Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

2006-09-01

This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD{sub 5} dose of sarin (42 {mu}g/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection.more » No guinea pig receiving 0.3, 0.4 or 0.5 x LD{sub 5} of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD{sub 5} of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD{sub 5} sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD{sub 5} sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD{sub 5} sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD{sub 5} sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD{sub 5} doses of sarin failed to habituate to some aspects of neurobehavioral testing. Spectral analysis of EEG data suggested that repeated sarin exposure may disrupt normal sleeping patterns (i.e., lower frequency bandwidths). While these EEG changes returned to relative normalcy 6 days after the last injection in animals receiving 0.4 x LD{sub 5} sarin, these changes were still observed in the animals that received 0.5 x LD{sub 5} sarin. Ten to twelve days after the last sarin injection (in 0.4 x LD{sub 5} group only), neurochemical data showed that striatal choline levels were reduced in comparison to the saline group. At this time, atropine sulfate (5 mg/kg, i.p.) challenge resulted in a transient elevation in striatal ACh levels in animals exposed to repeated 0.4 x LD{sub 5} sarin as well as in control animals. No evidence of brain or heart pathology was found in any guinea pig that survived all 10 sarin injections.« less

Denaverine hydrochloride and carbetocin increased welfare during and after parturition and enhanced subsequent fertility in cattle.

PubMed

Zobel, Robert; Taponen, Juhani

2014-01-01

The objectives of the current study were to investigate the influence of denaverine hydrochloride and carbetocin on softening and dilatation of the birth canal, the need for assistance during parturition, calf mortality, retention of fetal membranes, endometritis, and subsequent fertility. Altogether 200 animals (100 cows and 100 heifers) of the Simmental breed were divided into 2 groups: treatment (n = 100) and control (n = 100). Animals in the treatment group received denaverine hydrochloride and carbetocin (a maximum of twice for each, depending on the progression of labor) during delivery over a maximum of 4 waiting periods (30 min each), whereas control animals experienced the same waiting periods but received no treatment. The treatment protocol had a positive influence on the ease of calving and postpartum reproductive health. The treatment increased the number of animals with the birth canal dilated by more than 25 cm, and halved the need for any assistance at parturition. In addition, treatment decreased the occurrence of difficult calving, the need for episiotomy, the appearance of birth canal lesions, and clinical endometritis. The treatment protocol had an effect throughout the entire puerperal period, as treated animals conceived with fewer artificial inseminations (1.3 vs. 1.6 artificial inseminations/pregnancy) and sooner (67 vs. 78 d open) compared with control animals. Denaverine hydrochloride and carbetocin administered in combination during parturition affected the progression and ease of calving, and thus the welfare of cows in labor and subsequently. However, further studies are needed to confirm the findings and to establish best practices. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Industrial hemp decreases intestinal motility stronger than indian hemp in mice.

PubMed

Sabo, A; Horvat, O; Stilinovic, N; Berenji, J; Vukmirovic, S

2013-02-01

Indian hemp has shown beneficial effects in various gastrointestinal conditions but it is not widely accepted due to high content of tetrahydrocannabinol resulting in unwanted psychotropic effects. Since industrial hemp rich in cannabidiol lacks psychotropic effects the aim of research was to study the effects of industrial hemp on intestinal motility. Animals were randomly divided in six groups (each group consisting of 6 animals): Control group, Cind group - receiving indian hemp infuse for 20 days, Cids group-receiving industrial hemp infuse for 20 days, M group - treated with single dose of morphine (5 mg/kg i.m.) Cind+M group - treated with indian hemp infuse and single dose of morphine (5 mg/kg i.m.), Cids+M - treated with industrial hemp infuse and single dose of morphine (5 mg/kg i.m.). On the 20th day of the study animals were administered charcoal meal, and were sacrificed 35 minutes after administration. Intestinal motility was estimated according to distance between carbo medicinalis and cecum in centimeters. Decrease of intestinal motility in animals treated with indian hemp infuse was not significant compared to controls and it was smaller compared to animals treated with morphine (Indian hemp =15.43±10.5 cm, morphine = 20.14±5.87 cm). Strongest decrease of intestinal motility was recorded in animals treated with industrial hemp infuse, and it was significant compared to controls and morphine (industrial hemp = 26.5±9.90 cm, morphine = 20.14±5.87 cm; p < 0.005). Although not completely without psychotropic activity cannabidiol could be a potential replacement for tetrahydrocannabinol. Since industrial hemp infuse rich in cannabidiol reduces intestinal motility in healthy mice cannabidiol should be further evaluated for the treatment of intestinal hypermotility.

Efficacy of oral meloxicam suspension for prevention of pain and inflammation following band and surgical castration in calves.

PubMed

Olson, M E; Ralston, Brenda; Burwash, Les; Matheson-Bird, Heather; Allan, Nick D

2016-06-13

Castration is one of the most common procedures performed on beef and dairy cattle. The objective of the study was to determine the efficacy of meloxicam oral suspension in reducing pain and inflammation in calves following band or surgical castration. Two identical trials with the exception of the method of castration (Band Castration Study 1 and Surgical Castration Study 2) were conducted. Sixty (60) healthy Holstein calves 4 to 5 months of age (138-202 Kg) were used. Animals received either Meloxicam Oral Suspension at a dose of 1 mg/kg BW (n = 15 Study 1 and 15 Study 2) or Saline (n = 15 Study 1 and 15 Study 2) 2 h before castration. Physiological (Heart Rate, Plasma Cortisol and Plasma Substance P) and Behavioral (Visual Analog Scale (VAS), Accelerometers and tail Pedometers) evaluations were conducted before (day -1) and after Castration (Day 0, 1, 2, 3). Inflammation was evaluated daily by providing an individual animal score (Study1) or with a measurement of scrotal thickness (Study 2). Heart rates were significantly greater in control animals following band and surgical castration. Plasma cortisol and substance P were significantly reduced in animals receiving Meloxicam Oral Suspension. Control animals had significantly greater VAS scores. Accelerometers showed that meloxicam treated animals had a significantly greater motion index and number of steps as well as less % time lying and number of lying bouts. The scrotal inflammation (based on scrotal swelling) was significantly decreased in the meloxicam treated animals compared to the control animals on day 1, day 2 and 3. Meloxicam Oral Suspension was able to significantly reduce the display of painful behaviors and physiological responses to pain in band castrated and surgical castrated calves for up to 72 h following a single oral treatment of 1 mg/kg body weight. Meloxicam Oral Suspension was able to significantly reduce scrotal inflammation in band castrated and surgical castrated calves.

[Model of experimental nonalcoholic steatohepatitis from use of methionine and choline deficient diet].

PubMed

Zamin, Idilio; Mattos, Angelo Alves de; Mattos, Angelo Zambam de; Migon, Eduardo; Soares, Ernesto; Perry, Marcos Luiz Santos

2009-01-01

There are still many unknown aspects about nonalcoholic steatohepatitis, especially regarding its pathophysiology and pharmacological treatment. Thus, experimental models are important for a better understanding of this disease and the evaluation of the effects of drugs. To develop a model of experimental nonalcoholic steatohepatitis from use of methionine and choline deficient diet. Fifty Wistar male rats were studied. A methionine and choline deficient diet has been processed in a craft. A group of 40 animals received the deficient diet for 90 days, and a group of 10 rats (control group) received the standardized ration in the same period. After, the animals were killed by decapitation, and laparotomy was performed. Hepatectomy was performed and the liver was studied by macroscopy and microscopy. The level of significance considered was of 0,05. The rats that received the deficient diet showed significant loss of weight with findings from malnutrition and all of them had at least some degree of macrovesicular steatosis. The diagnosis of nonalcoholic steatohepatitis was performed in 27 (70%) of the 39 rats that received this deficient diet (1 rat died during the study). None of the 10 rats that received the standardized diet had histological abnormalities. The diet restricted in methionine and choline induced steatosis and steatohepatitis in an animal model with low cost.

An effective novel delivery strategy of rasagiline for Parkinson's disease.

PubMed

Fernández, Marcos; Negro, Sofía; Slowing, Karla; Fernández-Carballido, Ana; Barcia, Emilia

2011-10-31

This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to Wistar rats produced typical PD symptoms. Catalepsy, akinesia and swim tests outcomes in animals receiving RM either in solution or within microspheres showed a reversal in descent latency when compared to rotenone-treated animals, being this reversal specially pronounced in animals receiving RM microspheres (dose equivalent to 1 mg/kg/day RM injected i.p. every 15 days). Nissl-staining of brain sections showed selective degeneration of the substantia nigra (SNc) dopaminergic neurons in rotenone-treated animals which was markedly reverted by RM microspheres. PET/CT with (18)F-DG resulted in mean increases of accumulation of radiotracer in striatum and SNc of around 40% in animals treated with RM microspheres which also had significant beneficial effects on Bcl-2, Bax, TNF-α mRNA and SOD2 levels as detected by real-time RT-PCR. Our results confirm the robust effect achieved by the new controlled release system developed for RM which exhibited better in vivo efficacy than RM given in solution. Copyright © 2011 Elsevier B.V. All rights reserved.

Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator

PubMed Central

Mortazavi, SMJ; Mosleh-Shirazi, MA; Tavassoli, AR; Taheri, M; Mehdizadeh, AR; Namazi, SAS; Jamali, A; Ghalandari, R; Bonyadi, S; Haghani, M; Shafie, M

2013-01-01

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response. PMID:23930107

Effect of calabash chalk on the histomorphology of the gastro-oesophageal tract of growing wistar rats.

PubMed

Moses, B Ekong; Emma, E John; Christopher, C Mbadugha; Enobong I, Bassey; Theresa, B Ekanem

2012-01-01

Calabash chalk is a naturally occurring mineral consumed by members of some Nigerian communities for pleasure and by pregnant women as a remedy for morning sickness. The consumption of this geophagic material motivated our interest on the effect of the chalk on the histomorphology of the gastro-oesophageal tract. Twenty-eight young Wistar rats, 4 weeks old, were divided into 4 groups of equal size. Group 1 animals served as controls and received 1 mL of distilled water. Groups 2, 3, and 4 received orally 1 mL of a Calabash chalk suspension containing 40 mg/mL for 14, 21, and 28 days, respectively. Upon completion of the treatments, the animals in groups 2, 3, and 4 were sacrificed on days 15, 22, and 29, respectively, and the control group animals were sacrificed on day 29. All animals were euthanised using chloroform anaesthesia. The oesophagus and the stomach of each animal were dissected out and routinely processed for histological studies. There was oedema with haemorrhages in the mucosa of the stomach, and acanthosis, hyperkeratosis, and koilocytic changes were observed in the mucosa of the oesophagus of the groups treated with 40 mg/mL of Calabash chalk suspension. Calabash chalk caused histological changes to the stomach and the oesophagus that may lead to other pathophysiological conditions.

Effects of aqueous extract of kola nut (Cola Nitida Rubra) on reproductive hormones in rats.

PubMed

Adisa, W A; Otamere, H O; Osifo, C U; Idonije, O B; Nwoke, E O

2010-11-28

Our previous study suggests that aqueous extract of kola nut had effect on reproductive hormones in male rats. This study evaluates the effects of kola nut extract on plasma level of testosterone and luteinizing hormones in male rats. 30 adult male rats were used. These were divided into three groups: group A served as control and it received water only, group B and C received kola nut extract only (8mg/kg body weight), C served as recovery group. All the groups were treated for four weeks. The C which served as recovery group was allowed to recover for another four weeks at the end of the extract administration period. The plasma level of testosterone was significantly increased while that of luteinizing hormone was significantly decreased when compared with control animals. The recovery group showed values that were insignificantly lowered but a bit closer to those of the control animals. This showed that the rats were able to recover to some extent after the extract administration.

Bacterial infection and acute lung injury in hamsters.

PubMed

Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G

1986-07-01

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

PubMed Central

Carvalho, Ana Teresa; Souza, Heitor; Carneiro, Antonio Jose; Castelo-Branco, Morgana; Madi, Kalil; Schanaider, Alberto; Silva, Flavia; Pereira Jứnior, Fernando Antonio; Pereira, Márcia G; Tortori, Cláudio; Dines, Ilana; Carvalho, Jane; Rocha, Eduardo; Elia, Celeste

2007-01-01

AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn’s disease (CD). METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD. PMID:17465495

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production.

PubMed

Carvalho, Ana Teresa; Souza, Heitor; Carneiro, Antonio Jose; Castelo-Branco, Morgana; Madi, Kalil; Schanaider, Alberto; Silv, Flavia; Pereira Junior, Fernando Antonio; Pereira, Marcia G; Tortori, Claudio; Dines, Ilana; Carvalho, Jane; Rocha, Eduardo; Elia, Celeste

2007-04-21

To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor alpha (TNF-alpha), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohnos disease (CD). Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-alpha and IL-12 were quantified in the supernatant of organ cultures by ELISA. Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-alpha and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-alpha levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-alpha and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-alpha, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

[Influence of enzymatic hydrolyzate of mussel meat on growth and some indicators of general adaptation syndrome in rats].

PubMed

Sidorova, Iu S; Seliaskin, K E; Zorin, S N; Abramova, L S; Mazo, V K

2014-01-01

The impact of the 15-day consumption of enzymatic hydrolyzate of the mussels meat as a part of semi-synthetic diet on some stress biomarkers and apoptosis activity in various organs of growing male Wistar rats have been studied. Enzymatic hydrolyzate of the mussels meat (EMM) was obtained in pilot conditions using the enzyme preparation "Protozim". The animals of control group 1 (n = 8 with initial body weight of 179.4 ± 5.9 g) and experimental group 2 (n = 8, 176.3 ± 4.5 g) received a semi synthetic diet; the animals of the experimental group 3 (n = 8, 177.6 ± 4.0 g) received the same semi synthetic diet in which 50% of the casein was replaced by the peptides of EMM. On the penult day of the experiment animals of groups 2 and 3 were subjected to stress exposure by electric current on their paws (current 0.4 mA for 8 seconds) and were placed in metabolic cages for the collection of daily urine. At the 15th day of the study, all control and test animals were killed by decapitation under ether anesthesia and necropsied. The content of prostaglandin E2 and β-endorphin in blood plasma was determined by ELISA test. The concentration of urine corticosterone was measured by HPLC. DNA damage and percentage of apoptotic cells (apoptotic index) were calculated in thymus by single-cell gel electrophoresis assay (Comet assay). The relative body weight increase of animals treated with EMM was significantly (p < 0.05) higher (68.2 ± 3.0%) than those in animals of groups 1 and 2 (57.2 ± 4.0 and 59.7 ± 2.8%, respectively). The apoptotic index in thymus cells of tested groups of animals (2 and 3) was significantly (p < 0.05) higher (1.13 ± 0.09 and 1.09 ± 0.01%) compared to intact animals of control group (1.04 ± 0.01%). Determination of β-endorphin and prostaglandin E2 levels did not shown any significant differences between the groups. Significantly (p < 0.05) lower concentrations of corticosterone was found in the daily urine of stressed animals from group 3 (452 ± 78 ng/ml), treated with EMM, compared to stressed animals of group 2 that received a casein diet (834 ± 167 ng/ml). It has been shown that consumption of EMM with a high content of short and medium peptides has an impact on effectiveness of body weight gain of growing laboratory animals, and restrict the increase of corticosterone level in rats blood, which is typical for general adaptation syndrome.

The effectiveness of permethrin-treated deer stations for control of the Lyme disease vector Ixodes scapularis on Cape Cod and the Islands

EPA Science Inventory

The use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the Lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to Lyme disease risk management. Included among the attractive feature...

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

PubMed

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

2016-01-01

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

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

Healing process of incisor teeth of diabetic rats replanted after storage in milk.

PubMed

Ricieri, Camila Benez; Sonoda, Celso Koogi; Aranega, Alessandra Marcondes; Panzarini, Sônia Regina; Poi, Wilson Roberto; Sundefeld, Maria Lúcia Marçal Mazza; Okamoto, Tetuo

2009-06-01

Several local factors that influence the healing process of replanted teeth have been investigated. However, it remains unclear how systemic alterations, such as diabetes mellitus, affect the prognosis of these cases. The purpose of this study was to evaluate the healing process of incisors of non-controlled diabetic rats replanted after storage in bovine long shelf-life (UHT) whole milk. Thirty-two rats were randomly assigned to receive an endovenous injection of either citrate buffer solution (group I - control; n = 16) or streptozotocin dissolved in citrate buffer solution to induce diabetes (group II; n = 16). After confirmation of the diabetic status by analysis of the glycemic levels, the maxillary right incisor of each animal was extracted and immersed in milk for 60 min. The root canals of teeth were then instrumented, and were filled with a calcium hydroxide-based dressing and replanted into their sockets. All animals received systemic antibiotic and were killed by anesthetic overdose 10 and 60 days after replantation. The specimens containing the replanted teeth were removed, fixed, decalcified, and embedded in paraffin. Semi-serial 6-microm-thick sections were obtained and stained with hematoxylin and eosin for histologic and histometric analyses. The results showed that the connective tissue adjacent to the root surface was less organized in the diabetic animals than in the control animals in both periods; the root dentin was less severely affected by root resorption in the diabetic rats; there were no significant differences between the control and diabetic groups regarding the occurrence of replacement resorption and inflammatory resorption.

Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation

PubMed Central

Filgueiras, Claudio C.; Krahe, Thomas E.; Medina, Alexandre E.

2010-01-01

Deficits in learning and memory have been extensively observed in animal models of fetal alcohol spectrum disorders (FASD). Here we use the Morris Maze to test whether Vinpocetine, a Phosphodiesterase type 1 inhibitor, restores learning performance in rats exposed to alcohol during the third trimester equivalent of human gestation. Long Evans rats received ethanol (5 g/Kg ip) or saline on alternate days from postnatal day (P) 4 to P10. Two weeks later (P25), the latency to find a hidden platform was evaluated (2 trials per day spaced at 40-min inter-trial intervals) during 4 consecutive days. Vinpocetine treatment started on the first day of behavioral testing: animals received vinpocetine (20 mg/kg ip) or vehicle solution every other day until the end of behavioral procedures. Early alcohol exposure significantly affected the performance to find the hidden platform. The average latency of ethanol exposed animals was significantly higher than that observed for the control group. Treatment of alcohol-exposed animals with vinpocetine restored their performance to control levels. Our results show that inhibition of PDE1 improves learning and memory deficits in rats early exposed to alcohol and provide evidence for the potential therapeutic use of vinpocetine in FASD. PMID:20219634

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

PubMed Central

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

2004-01-01

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

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

PubMed

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

2004-10-01

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

Chronic combined hyperandrogenemia and western-style diet in young female rhesus macaques causes greater metabolic impairments compared to either treatment alone.

PubMed

True, C A; Takahashi, D L; Burns, S E; Mishler, E C; Bond, K R; Wilcox, M C; Calhoun, A R; Bader, L A; Dean, T A; Ryan, N D; Slayden, O D; Cameron, J L; Stouffer, R L

2017-09-01

Does developmental exposure to the combination of hyperandrogenemia and western-style diet (WSD) worsen adult metabolic function compared to either treatment alone? Young female rhesus macaques treated for 3 years, beginning at menarche, with combined testosterone (T) and WSD have increased weight gain and insulin resistance compared to controls and animals treated with either T or WSD alone. Hyperandrogenemia is a well-established component of polycystic ovary syndrome (PCOS) and can be observed in peripubertal girls, indicating a potential pubertal onset of the disease. Obesity is often associated with hyperandrogenemia in peripubertal girls, and overweight girls appear to be at higher risk for the development of PCOS later in life. Juvenile (2.5- year old) female rhesus macaques were divided into four groups (n = 10/group): control animals receiving cholesterol implants and a control diet with 15% of calories derived from fat (C), animals receiving T implants (mean serum levels: 1.35 ± 0.01 ng/ml) and a control diet (T), animals receiving a cholesterol implant and a WSD with 36% of calories derived from fat (WSD) and animals receiving a T implant and a WSD (T + WSD). Animals were maintained on the treatments for 36 months and were 5.5 years old at study completion. Metabolic testing consisted of body measurements including weight, dual-energy X-ray absorptiometry scans, activity monitoring, and glucose tolerance testing at zero months and at least once every 12 months for the remainder of the study. Indirect calorimetry and serum hormone assays were performed following 36 months of treatment. Body weight and fat mass gain were significantly increased in T + WSD at 24 and 36 months of treatment compared to the other three groups. Log transformed fasting insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were significantly increased in T + WSD animals at 3 years of treatment compared to all other groups. T-treatment caused a greater rate of decline in activity after 18 months, while food intake and metabolic rate were largely unaffected by treatments. Variability was present in the metabolic parameters measured; however, this is similar to the heterogeneity observed in human populations. Chronic hyperandrogenemia beginning at puberty may exacerbate metabolic dysfunction in women consuming a WSD and account for the increased rates of obesity and insulin resistance observed in PCOS patients. Counseling of female patient populations with elevated androgens about the potential benefit of consuming a lower fat diet could improve long-term metabolic health outcomes. Eunice Kennedy Shriver National Institute of Child Health & Human Development P50HD071836 and Oregon National Primate Center Grant P51 OD011092. The authors have no competing conflict of interests to disclose. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Animated graphics for comparing two risks: a cautionary tale.

PubMed

Zikmund-Fisher, Brian J; Witteman, Holly O; Fuhrel-Forbis, Andrea; Exe, Nicole L; Kahn, Valerie C; Dickson, Mark

2012-07-25

The increasing use of computer-administered risk communications affords the potential to replace static risk graphics with animations that use motion cues to reinforce key risk messages. Research on the use of animated graphics, however, has yielded mixed findings, and little research exists to identify the specific animations that might improve risk knowledge and patients' decision making. To test whether viewing animated forms of standard pictograph (icon array) risk graphics displaying risks of side effects would improve people's ability to select the treatment with the lowest risk profile, as compared with viewing static images of the same risks. A total of 4198 members of a demographically diverse Internet panel read a scenario about two hypothetical treatments for thyroid cancer. Each treatment was described as equally effective but varied in side effects (with one option slightly better than the other). Participants were randomly assigned to receive all risk information in 1 of 10 pictograph formats in a quasi-factorial design. We compared a control condition of static grouped icons with a static scattered icon display and with 8 Flash-based animated versions that incorporated different combinations of (1) building the risk 1 icon at a time, (2) having scattered risk icons settle into a group, or (3) having scattered risk icons shuffle themselves (either automatically or by user control). We assessed participants' ability to choose the better treatment (choice accuracy), their gist knowledge of side effects (knowledge accuracy), and their graph evaluation ratings, controlling for subjective numeracy and need for cognition. When compared against static grouped-icon arrays, no animations significantly improved any outcomes, and most showed significant performance degradations. However, participants who received animations of grouped icons in which at-risk icons appeared 1 at a time performed as well on all outcomes as the static grouped-icon control group. Displays with scattered icons (static or animated) performed particularly poorly unless they included the settle animation that allowed users to view event icons grouped. Many combinations of animation, especially those with scattered icons that shuffle randomly, appear to inhibit knowledge accuracy in this context. Static pictographs that group risk icons, however, perform very well on measures of knowledge and choice accuracy. These findings parallel recent evidence in other data communication contexts that less can be more-that is, that simpler, more focused information presentation can result in improved understanding. Decision aid designers and health educators should proceed with caution when considering the use of animated risk graphics to compare two risks, given that evidence-based, static risk graphics appear optimal.

Substitution of drinking water by fructose solution induces hyperinsulinemia and hyperglycemia in hamsters.

PubMed

Barros, Carlos Magno M R; Lessa, Rosane Q; Grechi, Mauricio P; Mouço, Tanial L M; Souza, Maria das Graças C; Wiernsperger, Nicolas; Bouskela, Eliete

2007-06-01

To test the possibility of obtaining a practical and stable model of hyperinsulinemia and hyperglycemia in hamsters, substituting the drinking water by 10% or 20% fructose solutions for a period of 2, 4, or 6 months. Male hamsters were divided into 3 main groups, further divided in 3 subgroups: Two months: Group Ia control (n = 51) received filtered water, Group Ib (n = 49) received 10% fructose solution instead of water, Group Ic (n=8) received 20% fructose solution instead of water. Four months: Group IIa control (n=8), Group IIb 10% fructose (n = 7), Group IIc 20% fructose (FIIc, n = 7). Six months: Group IIIa control (n = 6), Group IIIb 10% Fructose (n = 6), Group IIIc 20% Fructose (n = 5). All groups were fed with the same laboratory diet. The animals were weighed every 2 weeks during the study period. On the final day of each experiment (61st, 121st, and 181st day after the beginning of the study, respectively), the animals were weighed and anesthetized for blood collection to determine plasma glucose and insulin after at least a 12-h fast. Ten animals of group Ia and 10 of group Ib were evaluated to determine changes in macromolecular permeability induced by ischemia/reperfusion as measured in the cheek pouch microcirculation. Compared to controls, the animals that drank the 10% or 20% fructose solution had significantly greater weight gain (P < .001), fasting plasma glucose (P < .001) Reperfusion, after 30 min ischemia, resulted in an immediate but reversible increase in postcapillary leakage (L) of 89.0 +/- 2.0 L/cm(2) (group Ia - controls), and 116.5 +/- 4.8 L/cm(2) (group Ib 10% fructose), P < .001. These results suggest that chronic administration of either 10% or 20% fructose solutions could be used to experimentally induce a stable hamster model of hyperinsulinemia and hyperglycemia. The model might facilitate the study of basic mechanisms of hyperglycemia and hyperinsulinemia affecting the microvasculature as demonstrated by the findings regarding ischemia/reperfusion after only 2 months of treatment.

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

PubMed Central

Mata, Karina M; Prudente, Paula S; Rocha, Fabio S; Prado, Cibele M; Floriano, Elaine M; Elias, Jorge; Rizzi, Elen; Gerlach, Raquel F; Rossi, Marcos A; Ramos, Simone G

2011-01-01

Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60–70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process. PMID:21039990

Organic selenium supplementation increases PHGPx but does not improve viability in chilled boar semen.

PubMed

Martins, S M M K; De Andrade, A F C; Zaffalon, F G; Bressan, F F; Pugine, S M P; Melo, M P; Chiaratti, M R; Marino, C T; Moretti, A S; Arruda, R P

2015-02-01

This study evaluated the effects of dietary organic selenium (Se) on viability of chilled boar semen. Twelve boars were divided into three groups: control (CON), 0.3 mg kg(-1) sodium selenite; inorganic (INO), 0.5 mg kg(-1) sodium selenite and organic (ORG), 0.5 mg kg(-1) Se yeast. The experiment was conducted within 10 weeks, and analysis was performed fortnightly, in storage semen by 72 h. No effect was observed on motility; however, straightness and linearity percentages were higher (P < 0.05) in the animals receiving CON diet compared with INO group. Percentages of cells with both plasma and acrosomal intact membranes, lipidic membrane peroxidation and mitochondrial membrane potential were similar on all treatments. Animals receiving CON diet presented higher (P < 0.05) values of ATP when compared with INO group. The PHGPx was higher (P < 0.05) in animals that received ORG in comparison with INO group. In conclusion, organic selenium supplementation increases PHGPx but does not improve chilled semen viability in 72 h. © 2014 Blackwell Verlag GmbH.

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.

PubMed

Wanji, Samuel; Eyong, Ebanga-Echi J; Tendongfor, Nicholas; Ngwa, Che J; Esuka, Elive N; Kengne-Ouafo, Arnaud J; Datchoua-Poutcheu, Fabrice R; Enyong, Peter; Agnew, Dalen; Eversole, Rob R; Hopkins, Adrian; Mackenzie, Charles D

2017-07-01

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.

Antioxidant status and hormonal profile reflected by experimental feeding of probiotics.

PubMed

Ghoneim, Magdy A; Moselhy, Said S

2016-04-01

Excessive production of free radicals can result in tissue damage, which mainly involves generation of hydroxyl radical and other oxidants. Such free radical-induced cell damage appears to play a major role in the pathogenesis of many diseases. Probiotics have been used therapeutically to modulate immunity, improve digestive processes, lower cholesterol, treat rheumatoid arthritis, and prevent cancer. The proposed research was designed to evaluate the changes in oxidative and antioxidative profile in addition to metabolic-related hormones of living animal model, which may generally affect the health status. Two groups of rabbits (10 animals each) were allocated in hygienic cages of controlled animal house. Control group received standard diet, and the other group received the same diet containing one probiotic for 30 days. Lactate dehydrogenase (LDH) activity in leukocytes, blood glucose, reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were estimated in different tissues. Malondialdehyde (MDA) and total proteins were also determined in different tissues. Certain hormones related to metabolism and growth were also evaluated. Leukocytic LDH activity was significantly increased along with nonsignificant increase of blood glucose in probiotics-fed animals. Results showed significant decreases in the levels of triiodothyronine and thyroid-stimulating hormone but showed significant elevations in thyroxine, insulin, growth hormone, and testosterone levels in animals fed with probiotics. Total proteins content was highly significantly elevated in liver, kidneys, and muscles of probiotic-administered animals. Microsomal GSH level was significantly decreased only in skeletal muscles of probiotic-treated animals. MDA was significantly lowered in animal tissues fed with probiotics. GSH-Px activity was elevated in hepatic and muscular microsomes of probiotic-supplemented animals while it was nonsignificantly increased in renal microsomes. Microsomal SOD activity was elevated in liver, kidneys, and skeletal muscles of probiotics-administrated animals. It is concluded that supplementation of probiotic may enhance antioxidant efficacy and scavenge free radicals and thus may be used as a preventive measure for protection against free radicals-induced disorders. © The Author(s) 2013.

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

PubMed

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

2016-08-15

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

Effects of heat stress on some reproductive parameters of male cavie (Cavia porcellus) and mitigation strategies using guava (Psidium guajava) leaves essential oil.

PubMed

Ngoula, Ferdinand; Guemdjo Tekam, Maryvonne; Kenfack, Augustave; Tadondjou Tchingo, Cyrille D'Alex; Nouboudem, Sandrine; Ngoumtsop, Herman; Tsafack, Borice; Teguia, Alexis; Kamtchouing, Pierre; Galeotti, Marco; Tchoumboue, Joseph

2017-02-01

Climate changes, particularly the increase of temperature are among the main causes behind the decline of fertility in humans as well as animals. In this study, the effects of heat stress on some reproductive parameters of male cavies and mitigation strategies using guava leaves essential oil (GLEO) were studied. For this purpose, 40 male cavies aged 2.5-3 months and weighing between 348 and 446g were divided into 4 groups of 10 animals each and subjected to the following temperatures: Ambient temperature (20-25°C) for the control group, 35°C for group 1, 45°C for group 2 and 45°C+100µl GLEO/kg body weight, administered by gavage to animals for group 3. Exposure time of heat was 7h per day for 60 days. Results reveal that the relative weights of testes, epididymis, vas deferens and seminal vesicles were hardly affected by the temperature levels considered (P>0.05). The mass and individual sperm motility was significantly lower (P<0.05) in cavies exposed to the temperature of 35 and 45°C as compared with those which received GLEO and controls. The percentages of abnormal sperm and altered sperm DNA were higher in animals exposed to temperature of 35 and 45°C as compared with the controls. The activity of superoxide dismutase significantly increased (P<0.05) in animals exposed to temperature of 45°C and in those of 45°C and orally treated with GLEO, compared with cavies exposed to temperature of 45°C without receiving GLEO. The level of malondialdehyde was significantly increased (P<0.05) in animals exposed to temperature of 35 and 45°C, whereas the level of nitric oxide was significantly lower (P<0.05) in exposed animals as compared with controls. It was concluded that the exposure of male cavies at 35 and 45°C for 60 days induce heat stress that causes deterioration of sperm characteristics. These effects that can be mitigated by the administration of guava leaves essential oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of combined photobiomodulation and curcumin on skin wound healing in type I diabetes in rats.

PubMed

Soleimani, Hasan; Amini, Abdollah; Taheri, Soudabeh; Sajadi, Ensieh; Shafikhani, Sasha; Schuger, Lucia A; Reddy, Vijaya B; Ghoreishi, Seyed Kamran; Pouriran, Ramin; Chien, Sufan; Bayat, Mohammad

2018-04-01

The purpose of the present scientific study was to analyze the effects of combined pulsed wave Photobiomodulation (PW PBM) and Curcumin on the microbial flora; in addition, the tensiometrical wounds properties for type one diabetes mellitus (TIDM) in an experimental animal model. TIDM induction was performed in thirty rats. In the entire animals, one full-thickness excision was implemented on their backs. Randomly, the divisions of rats into 5 groups took place. The primary group was considered as the control group and did not receive any treatment. The secondary group (placebo) received sesame oil by gastric gavage. The third group received PWPBM (890 nm, 80 Hz, 0.2 J/cm 2 ). The fourth group received curcumin (40 mg/kg, which was dissolved in sesame oil) by gastric gavage. Eventually, the fifth group received PW PBM + curcumin. Precisely, on day 7, microbiological examinations, and on the 15th day microbiological and tensiometrical examinations were conducted. The data were analyzed by statistical tests. PW PBM, significantly exacerbated tensiometrical properties of the TIDM repairing wound. PW PBM, curcumin, and PWPBM + curcumin significantly decreased colony forming units compared to the control and the placebo groups indeed. It was remarkably attained that PW PBM significantly accelerated the process of wound healing in the STZ-induced TIDM. The PW PBM was statistically more compelling compared to the curcumin and PWPBM + curcumin. PW PBM, curcumin, and PWPBM + curcumin significantly decreased colony forming units compared to the control and placebo groups. Copyright © 2018. Published by Elsevier B.V.

[Polymer ocular implants for controlled release of drugs. I. Animal testing of the materials].

PubMed

Czechowicz-Janicka, K; Romaniuk, I; Piekarniak, A; Wicha-Brzuchalska, A; Galant, S; Rosiak, J

1992-01-01

Presented are the results of trials with hydrogel inserts received by radiation method and applied into the conjunctival sac of rabbits. In the future they can serve for incorporation of some definite drugs.

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.

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.

Increased caries-incidence by oral inoculation of cariogenic bacteria in rats after dietary fluoride

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

Clark, W.B.; Kreitzman, S.N.; Howell, T.H.

1976-04-01

The authors had previously observed that dietary NaF administered to rats during the formative and eruptive stages of tooth development does not significantly reduce the enamel solubility in acid buffer solution. They hypothesized that NaF reduces the cariogenicity of the bacterial flora. In order to test this hypothesis, rats from the same litter were divided into three groups all of which received a cariogenic diet. Group one received no fluoride. Groups two and three were supplemented with 50 ppm NaF, from day 1 to day 21. In the first study, one of the 21-day-old NaF-supplemented groups was inoculated by smearsmore » of fecal material from the control animals that did not receive NaF supplement. The second NaF group was not inoculated and served as control. In a second study, cariogenic Strep. mutans 6715 was used as the inoculum in place of the fecal smear. In both studies, the inoculation of a NaF group increased the caries to about 70% of the control group, while the mean scores on the non-inoculated NaF group were about 50% of the control group. These results indicate that alteration of the transmissible flora may be an important factor in the cariostatic action of dietary fluoride in experimental animals. This observation supports the suggestion that fluoride may alter the cariogenic flora.« less

Gene therapy by electroporation for the treatment of chronic renal failure in companion animals

PubMed Central

Brown, Patricia A; Bodles-Brakhop, Angela M; Pope, Melissa A; Draghia-Akli, Ruxandra

2009-01-01

Background Growth hormone-releasing hormone (GHRH) plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Companion dogs (13.1 ± 0.8 years, 29.4 ± 5.01 kg) and cats (13.2 ± 0.9 years, 8.5 ± 0.37 kg) received a single 0.4 mg or 0.1 mg species-specific plasmid injection, respectively, intramuscularly followed by electroporation, and analyzed up to 75 days post-treatment; controls underwent electroporation without plasmid administration. Results Plasmid-treated animals showed an increase in body weight (dogs 22.5% and cats 3.2%) compared to control animals, and displayed improved quality of life parameters including significant increases in appetite, activity, mentation and exercise tolerance levels. Insulin-like growth factor I (IGF-I, the downstream effector of GHRH) levels were increased in the plasmid treated animals. Hematological parameters were also significantly improved. Protein metabolism changes were observed suggesting a shift from a catabolic to an anabolic state in the treated animals. Blood urea nitrogen and creatinine did not show any significant changes suggesting maintenance of kidney function whereas the control animal's renal function deteriorated. Treated animals survived longer than control animals with 70% of dogs and 80% of cats surviving until study day 75. Only 17% and 40% of the control dogs and cats, respectively, survived to day 75. Conclusion Improved quality of life, survival and general well-being indicate that further investigation is warranted, and show the potential of a plasmid-based therapy by electroporation in preventing and managing complications of renal insufficiency. PMID:19149896

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice.

PubMed

Lara, Alessandra Cerávolo; Cândido, Eduardo Batista; Vidigal, Paula Vieira; Rocha, Ana Luiza Lunardi; Carvalho-Macedo, Alessandra Costa; Carneiro, Márcia Mendonça; Silva-Filho, Agnaldo Lopes

2016-04-01

To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

The effectiveness of permethrin-treated deer stations for control of the Lyme disease vector Ixodes scapularis on Cape Cod and the islands: a five year experiment

EPA Science Inventory

The use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the Lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to Lyme disease risk management. Included among the attractive features...

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

Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair.

PubMed

Tharappel, Job C; Harris, Jennifer W; Zwischenberger, Brittany A; Levy, Salomon M; Puleo, David A; Roth, J Scott

2016-05-01

Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats. Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting. In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control. It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.

Citrus pulp and wheat straw silage as an ingredient in lamb diets: effects on growth and carcass and meat quality.

PubMed

Scerra, V; Caparra, P; Foti, F; Lanza, M; Priolo, A

2001-04-01

Twenty "Merinizzata Italiana" lambs were introduced to two experimental diets. Ten animals (five males and five females, control group) received the traditional diet that is supplied by farmers in southern Italy, which comprised of oat hay ad libitum and commercial concentrate. The second group (the same number of lambs, silage group) received citrus pulp and wheat straw silage ad libitum and 70% of the commercial concentrate supplied to the control group. The animals were slaughtered after 80 days of feeding and carcass and some meat quality parameters were measured. No differences were observed for live weight between treatments, and carcass weights were similar for the two diets, but with obvious differences between sexes. Animals on silage produced carcasses with a better muscular conformation and with a lower fatness score (P<0.05). Subcutaneous fat colour was influenced by sex, being lighter in the female carcasses (P<0.05). Dissection of different anatomical parts showed a higher percentage of lean and a lower proportion of fat in silage samples compared to control ones. Ultimate pH was highly affected by sex being higher in the samples from male lambs (P<0.01), but was unaffected by diet treatment. Diet tended to affect meat shear force value which was lower in the silage samples, although, samples from all the animals were extremely tender. Meat from silage samples had a higher water content (P<0.05). Overall, in our experimental conditions, the use of citrus pulp silage seemed to be economically convenient for producing animals with substantially unmodified carcass and meat quality characteristics.

“Anatomy of an Illness”: Control from a caregiver’s perspective

PubMed Central

Laudenslager, Mark L.

2013-01-01

Caregivers of loved ones with chronic illnesses experience an uncontrollable challenge with potentially negative behavioral and medical consequences. Extensive research has demonstrated immune and endocrine regulation can be significantly disrupted by negative behavioral factors based on both animal models and human studies. However, fewer studies have focused on how psychosocial interventions might reverse the negative consequences of stressors such as caregiving. The distress of caring for individuals with cancer has only recently begun to receive attention. These interventions addressing caregiver distress are rare overall and caregivers of patients receiving hematopoietic stem cell transplants (HSCT) have received even less attention. HSCT caregivers report feelings of loss of control. Animal studies suggest that control over aversive events can mitigate the negative consequences of stressors. Caregivers of allogeneic HSCT patients for blood cancers must be available 24/7 for three months or longer following stem cell infusion to closely monitor the recipients’ health and well-being. Does establishing a greater sense of control have positive impacts on caregivers? A randomized control trial of a cognitive behavioral stress management intervention for allogeneic HSCT caregivers is briefly described. A model of caregiver mental health which may potentially impact the patient’s quality of life is proposed. These relationships exist in a complex system that includes genetic influences, sex, social environment, and prior experience. This system fits well within recent formulations of a “complexity science” approach to health and well-being. PMID:24012646

Neonatal isolation impairs neurogenesis in the dentate gyrus of the guinea pig.

PubMed

Rizzi, Simona; Bianchi, Patrizia; Guidi, Sandra; Ciani, Elisabetta; Bartesaghi, Renata

2007-01-01

In the current study we examined the effects of early isolation rearing on cell proliferation, survival and differentiation in the dentate gyrus of the guinea pig. Animals were assigned to either a standard (control) or an isolated environment a few days after birth (P5-P6), taking advantage of the precocious independence from maternal care of the guinea pig. On P14-P17 animals received one daily bromodeoxyuridine injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of brain-derived neurotrophic factor (BDNF). Though in absolute terms P45 isolated animals had less surviving cells, they showed no differences in survival rate and phenotype percent distribution compared to controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that P45 isolated animals had less (-42%) granule cells than controls. Results show that isolation rearing reduces hippocampal cell proliferation, likely by reducing BDNF expression and hampers migration of the new neurons to the granule cell layer, likely by altering density/morphology of radial glia cells. The large reduction in granule cell number following isolation rearing emphasizes the role of environmental cues as relevant modulators of neurogenesis.

The lack of effects of zinc and nitric oxide in initial state of pilocarpine-induced seizures.

PubMed

Noyan, Behzat; Jensen, Morten Skovgaard; Danscher, Gorm

2007-07-01

In this study we investigated whether intracerebroventricular (i.c.v.) injection of L-NAME (a nitric oxide synthase inhibitor) or CaEDTA (an extracellular zinc chelator) or the combination of the two could affect the initial phase of pilocarpine induced (2 h) seizures. Two groups of rats were used. Animals from both groups were given with i.c.v. injections of either saline (10 microl), L-NAME (150 microg/10 microl), CaEDTA (100 mM/10 microl) or L-NAME and CaEDTA. One group received pilocarpine HCl (380 mg/kg i.p.) the other served as control. Pilocarpine HCl was injected intraperitoneally 10 min later. The behavior of the animals was observed for 2h and the intensity of their seizures was scored. The rats were then sacrificed and their brains were removed and analyzed for zinc ions by using the immersion autometallography and the TSQ fluorescence staining. All the animals which received pilocarpine HCl developed seizures. Despite treatment with L-NAME and/or CaEDTA we found that the latency and the intensity of seizures were similar in both groups investigated. The distribution of stainable zinc ions and the intensity of staining in hippocampus were not affected by pilocarpine and found unchanged after L-NAME and/or CaEDTA injections in both the control animals and the pilocarpine treated animals. The data suggest that the nitric oxide system and zinc ions do not affect pilocarpine-induced seizures in their initial state.

Effects of intra-aortic balloon counterpulsation in a model of septic shock.

PubMed

Solomon, Steven B; Minneci, Peter C; Deans, Katherine J; Feng, Jing; Eichacker, Peter Q; Banks, Steven M; Danner, Robert L; Natanson, Charles; Solomon, Michael A

2009-01-01

Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high. The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols. Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 10(9) cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death. Compared with lower bacterial doses (4-7 x 10(9) colony-forming units/kg), control animals challenged with the highest dose (8 x 10(9) colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]O2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher FIO2) and positive end-expiratory pressure levels to maintain oxygenation (p < or = 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 microg/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function. In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.

Effect of resistant starch RS4 added to the high-fat diets on selected biochemical parameters in Wistar rats.

PubMed

Bronkowska, Monika; Orzeł, Dagmara; Łoźna, Karolina; Styczyńska, Marzena; Biernat, Jadwiga; Gryszkin, Artur; Zieba, Tomasz; Kapelko, Małgorzata

2013-01-01

Resistant starch (RS) is part of potato starch that is not digested in the gastrointestinal tract. RS4 is a chemically modified starch (for example by oxidation and esterification) and physically (by heating). The study was aimed at determining the effect of resistant starch on lipid metabolism and activity of hepatic enzymes in Wistar strain rats fed high-fat diets containing 15% of lard or 15% of soybean oil. Four types of diets were administered to the animals (4 groups of males, n = 32): control diet (K1) containing 15% of soybean oil; control diet (K2) containing 15% of lard as well as two groups receiving the same diets with 10% addition of resistant starch RS4 (K1S and K2S). The mean concentration of total cholesterol was lower in the group of animals fed a diet with vegetable oil (39.9 mg/dl) as compared to that reported in the group of rats fed the lard-supplemented diet (55.2 mg/dl). Compared to the control groups in both groups of animals receiving the diet supplemented with resistant starch RS4 the total cholesterol concentration in serum decreased by ca. 25% (differences were statistically significant). In groups of rats receiving oil- or lard-containing diets with the addition of the resistant starch preparation the concentration of triglycerides in serum decreased by ca. 47% and 10%, respectively. A beneficial effect of the resistant starch RS4 added to Wistar rats diets on the lipid metabolism has been shown. The concentrations of total cholesterol and triglycerides in the serum were lower and concentration of HDL-cholesterol was higher in the rats fed with the diets containing the addition of the RS4 preparation as compared to the control groups. Based on the activity of hepatic enzymes the degree of liver damage was lower in groups of rats fed with diets containing resistant starch RS4 as compared to the control groups.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Microanatomical effects of ethanolic extract of Cola nitida on the stomach mucosa of adult Wistar rats.

PubMed

Ojo, Gideon B; Nwoha, Polycarp U; Ofusori, David A; Ajayi, Sunday A; Odukoya, Samson A; Ukwenya, Victor O; Bamidele, Olubayode; Ojo, Olumide A; Oluwayinka, Oladele P

2009-10-15

The study investigated the microanatomical effects of the extracts of Cola nitida on the stomach mucosa of adult male Wistar rats. Twenty adult male wistar rats were randomly divided into four equal groups of A, B, C and D (n = 5). Animals in experimental groups B, C and D were given 600 mg/kg body weight of crude extract of Cola nitida each by oral intubation for five, seven and nine consecutive days respectively, while group A (control) received equivalent volume of distilled water. Twenty four hrs after the last administration, the animals were sacrificed; tissues were harvested and fixed in 10% formol saline for histological analysis. The study revealed necrotized surface epithelium, degenerated gastric mucosa, and loss of glandular elements in the stomachs of experimental groups' vis-à-vis the control group. These observations were days-dependent; as those groups which received the extract for higher number of days were seen to be adversely affected. In conclusion, Cola nitida at 600 mg/kg body weight can cause gastric lesion in animals. This lesion may be pronounced if the administration continued for days. Cola nitida should, therefore, be taken with caution to avoid gastric complications.

Schinus terebinthifolius raddi (Aroeira) and Orbignya phalerata mart. (Babassu) effect in cecorrahphy healing in rats.

PubMed

Scheibe, Christian Lamar; Ribas-Filho, Jurandir Marcondes; Czeczko, Nicolau Gregori; Malafaia, Osvaldo; Barboza, Luiz Eduardo Durães; Ribas, Fernanda Marcondes; Wendler, Eduardo; Torres, Orlando; Lovato, Fernanda Christo; Scapini, João Guilherme Seifert

2016-06-01

To evaluate the effect of Schinus terebinthifolius Raddi (aroeira) and Orbignya phalerata Mart. (babassu) in the healing process of cecorrhaphy in rats. : Fifty four rats were used, distributed into three groups randomly: aroeira, babassu and control, which were divided into three subgroups (six animals) according to the time of the deaths (7, 14, 21 days). All underwent the same surgical procedure, cecotomy and cecorrhaphy. The animals in group aroeira and babassu received daily dose of 100 mg/kg of hydroalcoholic extract and 50 mg/kg of aquous extract respectively, by gavage. The control group received only saline solution. The parameters evaluated were: macroscopic changes, ,resistance test to air insufflations and histological changes. : All animals showed good healing without infection. All groups presented adhesions between cecum and neighboring organs. The resistance test insufflating of atmospheric air showed progressive increase of pressure according to the days in the aroeira group, and decrease in babassu group, without significant difference. Microscopy showed significant difference in the polymorphonuclear, hyperemia, angiogenesis, fibroblast proliferation and collagen histological variables in the 14th day. : Hydroalcoholic extract of aroeira and the aqueous extract of babassu favored the healing process in cecorrhaphy in rats.

Individual intake and antiparasitic efficacy of free choice mineral containing fenbendazole for grazing steers.

PubMed

Garossino, K C; Ralston, B J; Olson, M E; McAllister, T A; Milligan, D N; Genswein, B M A

2005-04-20

A 95-day study (June 25-September 27, 2001) was conducted using 120 steers (311.9+/-2.4 kg) randomly allocated to two treatments: (1) mineral containing 0.55% fenbendazole (FBZ) and (2) control, no FBZ in the mineral. Animals in the FBZ group were individually identified by an electronic tag that was read each time an animal attended the mineral feeder. The feeder was equipped with load cells that enabled individual mineral intakes to be estimated. The FBZ group was provided with non-medicated mineral during a 14-day adaptation period (July 23-August 5) and an 8-day post-medication period (September 17-24). The intake of FBZ was monitored for 14 days during each of the two treatment periods; August 6-19 and September 3-16, separated by a 14-day non-medicated period, August 20-September 2. Control animals had access to non-medicated mineral for the entire 95-day study period. All steers were grazed on alfalfa-grass pasture for the duration of the study and had free access to flocculated, filtered and chlorinated water via an automatic waterer. Fecal samples were collected from steers three times during the experiment July 23, August 27 and September 27, and analyzed for nematode eggs and Giardia sp. cysts. Seventy-five and 83% of the steers in the FBZ group visited the mineral feeder during the first and second treatment periods, respectively. Individual daily mineral and FBZ intake for the first and second treatment periods was 52.9+/-6.6g per day and 10.1+/-1.2mg/kg BW; 72.3+/-8.4 g per day and 11.8+/-1.4 mg/kg BW, respectively. FBZ animals were separated into three groups during each treatment period based on the recommended dose (RD) of FBZ (5 mg/kg/BW), those that received > the RD, those that received < RD but > 50% RD and those that received < 50% of RD. Nematode egg counts and the number of animals infected with nematodes was reduced (p < 0.05) in all cattle that consumed FBZ as compared to control animals. In contrast to nematode eggs, numbers of Giardia cysts was not reduced (p > 0.05) by FBZ as compared to controls in either treatment period. These results may be a reflection of Giardia re-infection occurring following treatment and highlight the need for variation in treatment regimes specifically targeted at the parasite of interest.

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

PubMed

Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

2010-01-06

It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Effects of soy isoflavones on the concentration of hyaluronic acid in the vagina of type 1 diabetic rats.

PubMed

F Carbonel, A A; Azevedo Lima, P D; Lim, J J; Teixeira Borges, F; Rodrigues da Silva Sasso, G; Portugal Fuchs, L F; S Simões, R; Chada Baracat, E; Soares, J M; J Simões, M

2017-12-01

To assess the effects of isoflavones and 17β-estradiol on the vaginal epithelium extracellular matrix and hyaluronic acid (HA) in the diabetic rat model. Sixty adult, virgin, female rats underwent ovariectomy, then randomization into six groups of ten animals each: GI, sham ovariectomized control animals; GII, sham ovariectomized control diabetic animals; GIII, control ovariectomized rats receiving propylene glycol vehicle; GIV, control ovariectomized diabetic animals receiving propylene glycol vehicle; GV, diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI, ovariectomized diabetic rats treated with estrogen (17β-estradiol, 10 mg/kg, subcutaneously). Treatment took place over 30 consecutive days. After euthanasia, a portion of the vagina was immersed in liquid nitrogen for RT-qPCR and Western blotting. Another portion was processed for paraffin embedding. Sections were stained with hematoxylin & eosin for histomorphometry and Picro Sirius Red for collagen quantification. Vaginal epithelium histomorphometry in GIII (15.3 ± 1.1 µm) and GIV (14.5 ± 1.8 µm) was thinner than in GV (41.3 ± 1.5 µm) and GVI (74.3 ± 1.6 µm). There was an increase in collagen content in GV (84.1 ± 1.2 µm) and GVI (88.2 ± 1.7 µm). HA quantification was higher in GV (0.38 ± 1.1 μg/mg) and GVI (0.49 ± 1.4 μg/mg) when compared with GIII (0.12 ± 1.1 μg/mg) and GIV (0.10 ± 1.2 μg/mg), p < 0.05. Soy isoflavones increase hyaluronic acid concentration in the vagina of diabetic ovariectomized rats. Such findings might help to attenuate the effects of vulvovaginal atrophy in women.

90-Day oral toxicity study of D-tagatose in rats.

PubMed

Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

1999-04-01

D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

Effects of edaravone, a radical scavenger, on hepatocyte transplantation.

PubMed

Hayashi, Chihiro; Ito, Masahiro; Ito, Ryoutaro; Murakumo, Akiko; Yamamoto, Naoki; Hiramatsu, Noriko; Fox, Ira J; Horiguchi, Akihiko

2014-12-01

Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver-based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte-transplanted livers. Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 10(6) cells were injected in a 1.0-ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium-only; Group B received HTx only; and Group C received HTx and edaravone. Forty-eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide- and annexin-V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post-transplant days 0, 3, 5, 7, 10 and 14 using ELISA. The edaravone-treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone-treated liver sections also contained fewer TUNEL-positive cells and animals that received edaravone had higher serum albumin levels post-transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Anticoagulation therapy is harmful to large-sized cerebellar infarction.

PubMed

Zhang, She-Qing; Wang, Wei; Ma, Xiao-Long; Xia, Yu-Ye; Liu, Ai-Jun

2014-09-01

Anticoagulants are commonly used to treat ischemic stroke. Its impact on cerebellar infarction has not been fully understood. In the clinical study, we reviewed a consecutive series of patients with large-sized cerebellar infarction (diameter > 3 cm, n = 30) treated with or without anticoagulation. In animal study, cerebellar infarction operation was performed in 12 Cynomolgus monkeys. Then the animals were administrated with low molecular weight heparin (LMWH) or vehicle for 14 days. Six patients died during the following treatment. All the subjects that died received anticoagulation therapy, while nobody in the survival group received such a therapy. Compared with sham-operated animals, all monkeys with cerebellar infarction have obvious neurological deficits. The number and size of the Purkinje cells in the cerebellar area were also reduced. Two animals in the LMWH group (33%) died, while all animals in the vehicle control group survived. Compared with the vehicle group, the neurological score in the LMWH group was significantly increased (P < 0.05). The water content in the cerebella was also significantly higher (P < 0.05). Edema, hemorrhage, and subarachnoid hemorrhage occurred in the cerebella as well as brainstem of all the LMWH treated animals. These results indicated the harmful effects of anticoagulation therapy on large-sized cerebellar infarction. © 2014 John Wiley & Sons Ltd.

Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis.

PubMed

Unnikrishnan, Madathipat; Umashankar, P R; Viswanathan, Sidharth; Savlania, Ajay; Joseph, Roy; Muraleedharan, C V; Agrawal, Vivek; Shenoy, Sachin J; Krishnan, Lissy K; Mohanan, P V; Sabareeswaran, A

2017-11-01

Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.

Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis

PubMed Central

Unnikrishnan, Madathipat; Umashankar, P.R.; Viswanathan, Sidharth; Savlania, Ajay; Joseph, Roy; Muraleedharan, C.V.; Agrawal, Vivek; Shenoy, Sachin J.; Krishnan, Lissy K.; Mohanan, P.V.; Sabareeswaran, A.

2017-01-01

Background & objectives: Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Methods: Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Results: Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Interpretation & conclusions: Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals. PMID:29512608

Effects of ketamine-xylazine and isoflurane on insulin sensitivity in dehydroepiandrosterone sulfate-treated minipigs (Sus scrofa domestica).

PubMed

Heim, Kelly E; Morrell, Jesse S; Ronan, Anne M; Tagliaferro, Anthony R

2002-06-01

Isoflurane and ketamine-xylazine (KX) combinations are widely used veterinary anesthetics, KX being the particularly common agent for immobilizing swine. Results of previous studies indicate that KX and xylazine suppress insulin release. The steroid hormones, dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS), have variable effects on insulin sensitivity in animals. We evaluated the effect of DHEAS on plasma glucose and insulin concentrations in female Yucatan swine under KX and isoflurane anesthesia. A 2 x 2 factorial design was used. Twenty-four 17-week-old gilts were randomly assigned to receive vehicle (placebo) or DHEAS as part of an ongoing study. The KX was given intramuscularly to all animals prior to blood sample collection at weeks two and four. At week three, all animals received isoflurane by inhalation. During KX anesthesia, mean insulin concentration in DHEAS-treated and control groups approximated half the postisoflurane values (P < 0.001). While under isoflurane, the DHEAS group had significantly higher mean plasma insulin concentration and mean insulin-to-glucose ratio, compared with values for controls (P < 0.05). These findings are consistent with changes in insulin values following DHEAS treatment observed previously in nonanesthetized swine. The effect of DHEAS treatment was absent in animals under KX anesthesia. These results suggest that KX significantly decreases plasma insulin concentration and blunts DHEAS-associated insulin resistance in female minipigs.

Assessment of fluoride-induced changes on physicochemical and structural properties of bone and the impact of calcium on its control in rabbits.

PubMed

Gopalakrishnan, Subarayan Bothi; Viswanathan, Gopalan

2012-03-01

Bone deformities caused by the chronic intake of large quantities of fluoride and the beneficial effect of calcium on its control have been studied for many years, but only limited data are available on the quantitative effect of fluoride intake and the beneficial impact of calcium on fluoride-induced changes in bone at the molecular level. It is necessary to determine the degree of fluoride-induced changes in bone at different levels of fluoride intake to evaluate the optimum safe intake level of fluoride for maintaining bone health and quality. The ameliorative effect of calcium at different dose levels on minimizing fluoride-induced changes in bone is important to quantify the amount of calcium intake necessary for reducing fluoride toxicity. Thirty rabbits, 2 months old, were divided into five groups. Group I animals received 1 mg/l fluoride and 0.11% calcium diet; groups II and III received 10 mg/l fluoride and diet with 0.11% or 2.11% calcium, respectively; and groups IV and V received 150 mg/l fluoride and diet with 2.11% or 0.11% calcium, respectively. Analysis of bone density, ash content, fluoride, calcium, phosphorus, and Ca:P molar ratio levels after 6 months of treatment indicated that animals that received high fluoride with low-calcium diet showed significant detrimental changes in physicochemical properties of bone. Animals that received fluoride with high calcium intake showed notable amelioration of the impact of calcium on fluoride-induced changes in bone. The degree of fluoride-induced characteristic changes in structural properties such as crystalline size, crystallinity, and crystallographic "c"-axis length of bone apatite cells was also assessed by X-ray diffraction and Fourier transform infrared studies. X-ray images showed bone deformity changes such as transverse stress growth lines, soft tissue ossification, and calcification in different parts of bones as a result of high fluoride accumulation and the beneficial role of calcium intake on its control.

Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; OʼReilly, Barry A; McMahon, Stephen B

2017-01-01

Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.

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.

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.

Watching from a distance: A robotically controlled laser and real-time subject tracking software for the study of conditioned predator/prey-like interactions.

PubMed

Wilson, James C; Kesler, Mitch; Pelegrin, Sara-Lynn E; Kalvi, LeAnna; Gruber, Aaron; Steenland, Hendrik W

2015-09-30

The physical distance between predator and prey is a primary determinant of behavior, yet few paradigms exist to study this reliably in rodents. The utility of a robotically controlled laser for use in a predator-prey-like (PPL) paradigm was explored for use in rats. This involved the construction of a robotic two-dimensional gimbal to dynamically position a laser beam in a behavioral test chamber. Custom software was used to control the trajectory and final laser position in response to user input on a console. The software also detected the location of the laser beam and the rodent continuously so that the dynamics of the distance between them could be analyzed. When the animal or laser beam came within a fixed distance the animal would either be rewarded with electrical brain stimulation or shocked subcutaneously. Animals that received rewarding electrical brain stimulation could learn to chase the laser beam, while animals that received aversive subcutaneous shock learned to actively avoid the laser beam in the PPL paradigm. Mathematical computations are presented which describe the dynamic interaction of the laser and rodent. The robotic laser offers a neutral stimulus to train rodents in an open field and is the first device to be versatile enough to assess distance between predator and prey in real time. With ongoing behavioral testing this tool will permit the neurobiological investigation of predator/prey-like relationships in rodents, and may have future implications for prosthetic limb development through brain-machine interfaces. Copyright © 2015 Elsevier B.V. All rights reserved.

[Treatment of keratitis superficialis chronica of the dog with strontium 90].

PubMed

Höcht, Stefan; Grüning, Georg; Allgoewer, Ingrid; Nausner, Martin; Brunnberg, Leo; Hinkelbein, Wolfgang

2002-02-01

Corneal pannus is a disease which, if untreated, nearly always is progressive and may lead to blindness of the affected dog. A therapeutic standard is yet to be defined. Beta-ray irradiation with Sr-90 is often recommended on a casuistic basis, but systematic studies are sparse. The aim of the present study was to evaluate efficacy and to document side effects of radiotherapy with Sr-90. 17 animals were treated. 13 of them received treatment of 15 Gy surface dose twice within 2 days with additional medical therapy with ciclosporin and prednisolon. Only the more affected eye was treated with radiation which was applied with an eye-applicator, the other eye served as control. Four animals with already advanced impairment of vision received keratectomy, afterwards radiation was applied on both sides. Medical treatment alone led to deterioration in vascularization and spread of pigmentation in eleven of 13 (85%) of the control-eyes, density of pigmentation increased in eight of 13 (62%). After radiation therapy, almost all animals showed a marked initial improvement. Even if progressive disease occurred later on, further worsening as it happened in the control-eyes could be stopped in nine resp. ten of 13 eyes (69% and 77%). All animals with keratectomy and radiotherapy regained and preserved adequate vision. Besides short-term blepharospasm, no side effects were recorded. Corneal pannus is responsive to radiation therapy with Sr-90 and long-term benefit can be achieved. Side effects are minimal. Optimal sequencing of therapy and dosage still have to be examined.

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.

Reduction of Carriage of Enterohemorrhagic Escherichia coli O157:H7 in Cattle by Inoculation with Probiotic Bacteria

PubMed Central

Zhao, Tong; Doyle, Michael P.; Harmon, Barry G.; Brown, Cathy A.; Mueller, P. O. Eric; Parks, Andrew H.

1998-01-01

Bacteria inhibitory to Escherichia coli O157:H7 were isolated from cattle and evaluated for their potential for reducing carriage of E. coli O157:H7 in calves. Eighteen of 1,200 bacterial isolates from cattle feces and intestinal tissue samples were screened and determined to inhibit the growth of E. coli O157:H7 in vitro. Seventeen of the isolates were E. coli and one was Proteus mirabilis. None produced Shiga toxin. Genomic DNA fingerprinting by pulsed-field gel electrophoresis revealed 13 distinguishable profiles among the 18 isolates. Two calves inoculated perorally with a mixture of all 18 isolates (1010 CFU) appeared to be normal and did not develop signs of clinical disease throughout a 25- to 27-day observation period. These bacteria colonized segments of the gastrointestinal tract and were in feces at the termination of the experiment (25 and 27 days postinoculation) at levels of 50 to 200 CFU/g. Fifteen cannulated calves were studied to determine the efficiency of the probiotic bacteria in reducing or eliminating the carriage of E. coli O157:H7. Nine calves served as controls, with each animal receiving perorally 1010 CFU of E. coli O157:H7. E. coli O157:H7 was detected intermittently in the rumen samples from all control animals throughout 3 weeks postinoculation, whereas E. coli O157:H7 was shed at various levels in feces continuously throughout the experiment (mean, 28 days). E. coli O157:H7 was isolated from the rumens and colons of eight of nine and nine of nine calves, respectively, at the termination of the study. Six calves each received perorally 1010 CFU of probiotic bacteria and then 2 days later received 1010 CFU of E. coli O157:H7. E. coli O157:H7 was detected in the rumen for only 9 days postinoculation in two animals, for 16 days in one animal, for 17 days in two animals, and for 29 days in one animal. E. coli O157:H7 was detected in feces for only 11 days postinoculation in one animal, for 15 days in one animal, for 17 days in one animal, for 18 days in one animal, for 19 days in one animal, and for 29 days in one animal. At the end of the experiment (mean, 30 days), E. coli O157:H7 was not recovered from the rumen of any of the six animals treated with probiotic bacteria; however, E. coli O157:H7 was recovered from the feces of one of the animals. This animal was fasted twice postinoculation. These studies indicate that selected probiotic bacteria administered to cattle prior to exposure to E. coli O157:H7 can reduce the level of carriage of E. coli O157:H7 in most animals. PMID:9508288

Assessment of the efficacy of tilmicosin phosphate to eliminate Actinobacillus pleuropneumoniae from carrier pigs

PubMed Central

2005-01-01

Abstract The aim of this study was to evaluate the efficacy of in-feed medication with tilmicosin phosphate in order to eliminate or reduce the carriage of Actinobacillus pleuropneumoniae in the tonsils of carrier pigs. Two groups of 6 carrier animals received either a non-medicated feed (control group) or feed medicated with 400 ppm of tilmicosin phosphate (treated group) for 30 d. Three sentinel pigs were then introduced in each group and left for 29 d. The presence of A. pleuropneumoniae in tonsils was monitored using several techniques, including polymerase chain reaction (PCR). At the end of the treatment all of the control animals, but only 1 treated pig, were positive by PCR from tonsillar surface material. However, at necropsy, all control and most treated animals, as well as 1 sentinel animal, in both groups were positive by PCR from whole tonsils. In conclusion, under the experimental conditions, in-feed treatment with 400 ppm of tilmicosin phosphate significantly reduced the presence of A. pleuropneumoniae on the surface of tonsils but was unable to completely eliminate the organism from deeper tonsillar tissues and to prevent bacterial shedding by carrier animals. PMID:15971680

Assessment of the efficacy of tilmicosin phosphate to eliminate Actinobacillus pleuropneumoniae from carrier pigs.

PubMed

Fittipaldi, N; Klopfenstein, C; Gottschalk, M; Broes, A; Paradis, M A; Dick, C P

2005-04-01

The aim of this study was to evaluate the efficacy of in-feed medication with tilmicosin phosphate in order to eliminate or reduce the carriage of Actinobacillus pleuropneumoniae in the tonsils of carrier pigs. Two groups of 6 carrier animals received either a non-medicated feed (control group) or feed medicated with 400 ppm of tilmicosin phosphate (treated group) for 30 d. Three sentinel pigs were then introduced in each group and left for 29 d. The presence of A. pleuropneumoniae in tonsils was monitored using several techniques, including polymerase chain reaction (PCR). At the end of the treatment all of the control animals, but only 1 treated pig, were positive by PCR from tonsillar surface material. However, at necropsy, all control and most treated animals, as well as 1 sentinel animal, in both groups were positive by PCR from whole tonsils. In conclusion, under the experimental conditions, in-feed treatment with 400 ppm of tilmicosin phosphate significantly reduced the presence of A. pleuropneumoniae on the surface of tonsils but was unable to completely eliminate the organism from deeper tonsillar tissues and to prevent bacterial shedding by carrier animals.

Reciprocity in group-living animals: partner control versus partner choice.

PubMed

Schino, Gabriele; Aureli, Filippo

2017-05-01

Reciprocity is probably the most debated of the evolutionary explanations for cooperation. Part of the confusion surrounding this debate stems from a failure to note that two different processes can result in reciprocity: partner control and partner choice. We suggest that the common observation that group-living animals direct their cooperative behaviours preferentially to those individuals from which they receive most cooperation is to be interpreted as the result of the sum of the two separate processes of partner control and partner choice. We review evidence that partner choice is the prevalent process in primates and propose explanations for this pattern. We make predictions that highlight the need for studies that separate the effects of partner control and partner choice in a broader variety of group-living taxa. © 2016 Cambridge Philosophical Society.

Intestinal lymphocyte subsets and turnover are affected by chronic alcohol consumption: implications for SIV/HIV infection.

PubMed

Poonia, Bhawna; Nelson, Steve; Bagby, Greg J; Veazey, Ronald S

2006-04-15

We recently demonstrated that simian immunodeficiency virus (SIV) viral loads were significantly higher in the plasma of rhesus macaques consuming alcohol compared with controls following intrarectal SIV infection. To understand the possible reasons behind increased viral replication, here we assessed the effects of chronic alcohol consumption on distribution and cycling of various lymphocyte subsets in the intestine. Macaques were administered alcohol (n = 11) or sucrose (n = 12), and percentages of memory and naive and activated lymphocyte subsets were compared in the blood, lymph nodes, and intestines. Although minimal differences were detected in blood or lymph nodes, there were significantly higher percentages of central memory (CD95+CD28+) CD4+ lymphocytes in the intestines from alcohol-receiving animals before infection compared with controls. In addition, higher percentages of naive (CD45RA+CD95-) as well as CXCR4+CD4 cells were detected in intestines of alcohol-treated macaques. Moreover, alcohol consumption resulted in significantly lower percentages of effector memory (CD95+CD28-) CD8 lymphocytes as well as activated Ki67+CD8 cells in the intestines. A subset (7 receiving alcohol and 8 receiving sucrose) were then intrarectally inoculated with SIV(mac251). Viral RNA was compared in different tissues using real-time PCR and in situ hybridization. Higher levels of SIV replication were observed in tissues from alcohol-consuming macaques compared with controls. Central memory CD4 lymphocytes were significantly depleted in intestines and mesenteric lymph nodes from all alcohol animals at 8 weeks postinfection. Thus, changes in the mucosal immune compartment (intestines) in response to alcohol are likely the major reasons behind higher replication of SIV observed in these animals.

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

PubMed

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

1998-07-01

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

The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

PubMed

Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

2017-03-30

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Exercise x BCAA Supplementation in Young Trained Rats: What are their Effects on Body Growth?

PubMed

de Campos-Ferraz, Patricia Lopes; Ribeiro, Sandra Maria Lima; Luz, Silmara Dos Santos; Lancha, Antonio Herbert; Tirapegui, Julio

2011-01-01

The purpose of this study was to evaluate whether Branched-chain amino acids (BCAAs) supplementation had any beneficial effects on growth and metabolic parameters of young rats submitted to chronic aerobic exercise. Thirty-two young rats (age: 21-d) were randomly assigned to four experimental groups (n = 8): Supplemented Trained (Sup/Ex), Control Trained (Ctrl/Ex), Supplemented Sedentary (Sup/Sed) and Control Sedentary (Ctrl/Sed). The trained groups underwent a five-week swimming protocol and received supplemented (45 mg BCAA/body weight/day) or control ration. Trained animals presented a lower body length and a higher cartilage weight, regardless of supplementation. Physical activity was responsible for a substantial reduction in proteoglycan synthesis in cartilage tissue, and BCAA supplementation was able to attenuate this reduction and also to improve glycogen stores in the liver, although no major differences were found in body growth associated to this supplementation. Key pointsCartilage proteoglycan synthesis was dramatically reduced in trained animals as a whole.BCAA supplementation augmented liver glycogen stores and reduced proteolysis in our experimental conditionsTrained animals receiving BCAA supplementation featured increased proteoglycan synthesis compared to sedentary ones, probably because BCAA may have attenuated the negative effects of exercise on cartilage development.BCAA supplementation was not capable of neutralizing directly the negative effects of long-term physical training and lower food intake in young male rats on body growth.

[Lack of protection against gentamicin ototoxicity by auditory conditioning with noise].

PubMed

Strose, Alex; Hyppolito, Miguel Ângelo; Colombari, Gleice Cristina; Rossato, Maria; Oliveira, Jose Antônio Aparecido de

2014-01-01

Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful exposure. To confirm if conditioning with an agent different from that used to cause the trauma can also be effective. This was an experimental study with 17 guinea pigs, divided into three groups: an ototoxic control group (Cont) that received intramuscular administration of gentamicin 160 mg/kg/day for ten consecutive days, but no sound exposure; a sound control group (Sound) that was exposed to 85 dB broadband noise centered at 4 kHz, 30 min each day for ten consecutive days, but received no ototoxic medications; and an experimental group (Expt) that received sound exposure identical to the Sound group and after each noise presentation, received gentamicin similarly to Cont group. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs), brainstem auditory evoked potentials (BAEPs), and scanning electron microscopy. The animals that were conditioned with noise did not show any protective effect compared with the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. Conditioning with 85 dB broadband noises, 30 min a day for ten consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg/day for ten consecutive days in the guinea pig. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER'S DISEASE.

PubMed

Borhani, Mona; Sharifzadeh, Mohammad; Farzaei, Mohammad Hosein; Narimani, Zahra; Sabbaghziarani, Fatemeh; Gholami, Mahdi; Rahimi, Roja

2017-01-01

Alzheimer's disease (AD) is the most common cause of dementia that is an irretrievable chronic neurodegenerative disease. In the current study, we have examined the therapeutic effects of Iris germanica extract on Amyloid β (Aβ) induced memory impairment. Wistar rats were divided into five groups of 8 per each. Groups were as followed: control group which were normal rats without induction of AD, Aβ group which received Aβ (50 ng/side), iris 100 group which received Aβ + Iris (100 mg/kg), iris 200 group which received Aβ + Iris (200 mg/kg), and iris 400 group which received Aβ + Iris (400 mg/kg). AD was established by intrahippocampal injection of 50 ng/μl/side Aβ1-42. The day after surgery, animals in treatment groups received different doses of the aqueous extract of Iris by gavage for 30 days. Morris water maze test (MWM) was performed to assess the effects of I. germanica on learning and memory of rats with Aβ induced AD. Data from MWM tests, including escape latency and traveled distance, demonstrated that I. germanica extract could markedly improve spatial memory in comparison to control. Moreover, the plant had a significantly better effect on the performance of AD rats in the probe test. I. germanica extract can successfully reverse spatial learning dysfunction in an experimental model of AD. Further neuro psyco-pharmacological studies are mandatory to reveal the mechanism of action of this natural remedy in the management of AD symptoms.

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

PubMed

Silverstein, R J; Landsman, A S

1999-01-01

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

Biotelemetry implant volume and weight in rats: A pilot study report

NASA Technical Reports Server (NTRS)

Somps, Chris J.

1994-01-01

This paper reports the results of a pilot study in which a 240-gram rat was implanted for 41 days with biotelemetry devices weighing a total of 36 gm (18 cc). The implanted animal showed no differences in weight gain, food and water consumption, and postnecropsy organ weights when compared to both an unoperated control animal and an animal that underwent surgery but did not receive an implant. The implanted animal also had temperature and activity rhythms similar to those reported using much smaller implants. Thus, this pilot study showed that a 240-gm rat could be implanted with biotelemetry devices weighing nearly 15 percent of body weight without significant changes in health or behavior. A larger study involving more animals and similar implant sizes is recommended.

Methodological considerations on descriptive studies of induced periodontal diseases in rats.

PubMed

Galvão, Mariane Ponzio; Chapper, Ana; Rösing, Cassiano Kuchenbecker; Ferreira, Maria Beatriz; de Souza, Maria Antonieta

2003-01-01

The aim of this study was to show the technique and the methodological approach used in describing histological characteristics of induced periodontal disease in rats. To reach that inflammatory process, periodontal disease was induced by ligature, with or without sucrose-rich diet. Twenty-four female adult (60 days old) Wistar rats were divided in four groups: Group 1, or control (which received standard diet), Group 2 (which received ligature around the upper second molars and a standard diet), Group 3 (which received a sucrose-rich diet), and Group 4 (which received ligature around the upper second molars and a sucrose-rich diet). The animals were followed for a period of 30 days, after which they were sacrificed. The upper second molars were removed, processed, and the histological characteristics were analyzed by a descriptive dichotomous method. The results were analyzed by the Fisher's exact test (significance level of 95%) and by a residual test, which showed the relation between groups and histological characteristics. The animals which received ligature (Groups 2 and 4) showed histological characteristics related with periodontitis, whilst the animals without ligatures showed no periodontal destruction. This was shown by a distribution of these groups in extremes of a graphic representation. The use of a ligature, as done in this study, was able to promote a chronic inflammatory process in the periodontium of rats, regardless of the adopted diet. The correspondence factorial analysis was capable of showing these characteristics, being one more tool to be used in histological research.

Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint

PubMed Central

Zopf, David A.; Flanagan, Colleen L.; Wheeler, Matthew; Hollister, Scott J.; Green, Glenn E.

2015-01-01

Importance The study demonstrates an application for 3-dimensional (3D) printing that may serve as an effective intervention for severe tracheobronchomalacia. Objective A novel 3D printed, bioresorbable airway splint is tested for efficacy in extending survival in an animal model of severe, life-threatening tracheobronchomalacia. Participants Evaluation of an external airway splint for severe, life-threatening tracheobronchomalacia in a porcine animal model. Setting Multi-institutional and multidisciplinary collaboration between biomedical engineering laboratories and an academic animal surgery center. Interventions Experimental analysis of a 3D printed, bioresorbable airway splint is assessed in a porcine animal model of life-threatening tracheobronchomalacia. The open-cylindrical, bellow shaped porous polycaprolactone splint is placed externally and designed to suspend the underlying collapsed airway. Control animals (n=3) undergoing tracheal cartilage division and inner tracheal lumen dissociation and experimental animals (n=3) receiving the same model with overlying placement of the newly developed airway splint were evaluated. Main Outcomes and Measures An animal model for severe, life-threatening tracheobronchomalacia is proposed. Complete or near complete tracheal lumen collapse was observed in each animal with resolution of symptoms in all of the experimental animals after splint placement. Using our severe tracheobronchomalacia animal model, survival was significantly longer in duration in the experimental group receiving the airway splint after model creation when compared to model creation alone (p = 0.0495). Mortality in the experimental group was related to infection. Conclusions A multidisciplinary effort producing a CAD/CAM, bioresorbable tracheobronchial splint was tested in a porcine model of severe tracheomalacia and was found to extend survival. PMID:24232078

Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

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

Oldfield, E.H.; Friedman, R.; Kinsella, T.

1990-05-01

To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the othermore » two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.« less

Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles.

PubMed

Donaldson, Zoe R; Spiegel, Lauren; Young, Larry J

2010-02-01

The neuropeptide arginine vasopressin (AVP) modulates a variety of species-specific social behaviors. In socially monogamous male prairie voles, AVP acts centrally via vasopressin V1a receptor (V1aR) to facilitate mating induced partner preferences. The display of a partner preference requires at least 2 temporally distinct processes: social bond formation as well as its recall, or expression. Studies to date have not determined in which of these processes V1aR acts to promote partner preferences. Here, male prairie voles were administered intracerebroventricularly a V1aR antagonist (AVPA) at different time points to investigate the role of V1aR in social bond formation and expression. Animals receiving AVPA prior to cohabitation with mating or immediately prior to partner preference testing failed to display a partner preference, while animals receiving AVPA immediately after cohabitation with mating and control animals receiving vehicle at all 3 time points displayed partner preferences. These results suggest that V1aR signaling is necessary for both the formation and expression of partner preferences and that these processes are dissociable. (c) 2009 APA, all rights reserved.

Alpha lipoic acid (ALA) modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2).

PubMed

Dixit, Shilpi; Dhar, Pushpa; Mehra, Raj D

2015-01-01

The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic ( iAs ) induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO 2 (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs . Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs , thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

Toxicology and carcinogenesis studies of a nondecolorized [corrected] whole leaf extract of Aloe barbadensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice (drinking water study).

PubMed

Boudreau, M D; Beland, F A; Nichols, J A; Pogribna, M

2013-08-01

Extracts from the leaves of the Aloe vera plant (Aloe barbadensis Miller) have long been used as herbal remedies and are also now promoted as a dietary supplement, in liquid tonics, powders or tablets, as a laxative and to prevent a variety of illnesses. We studied the effects of Aloe vera extract on rats and mice to identify potential toxic or cancer-related hazards. We gave solutions of nondecolorized extracts of Aloe vera leaves in the drinking water to groups of rats and mice for 2 years. Groups of 48 rats received solutions containing 0.5%, 1% or 1.5% of Aloe vera extract in the drinking water, and groups of mice received solutions containing 1%, 2%, or 3% of Aloe vera extract. Similar groups of animals were given plain drinking water and served as the control groups. At the end of the study tissues from more than 40 sites were examined for every animal. In all groups of rats and mice receiving the Aloe vera extract, the rates of hyperplasia in the large intestine were markedly increased compared to the control animals. There were also increases in hyperplasia in the small intestine in rats receiving the Aloe vera extract, increases in hyperplasia of the stomach in male and female rats and female mice receiving the Aloe vera extract, and increases in hyperplasia of the mesenteric lymph nodes in male and female rats and male mice receiving the Aloe vera extract. In addition, cancers of the large intestine occurred in male and female rats given the Aloe vera extract, though none had been seen in the control groups of rats for this and other studies at this laboratory. We conclude that nondecolorized Aloe vera caused cancers of the large intestine in male and female rats and also caused hyperplasia of the large intestine, small intestine, stomach, and lymph nodes in male and female rats. Aloe vera extract also caused hyperplasia of the large intestine in male and female mice and hyperplasia of the mesenteric lymph node in male mice and hyperplasia of the stomach in female mice.

Short-term glycemic control is effective in reducing surgical site infection in diabetic rats.

PubMed

Kroin, Jeffrey S; Buvanendran, Asokumar; Li, Jinyuan; Moric, Mario; Im, Hee-Jeong; Tuman, Kenneth J; Shafikhani, Sasha H

2015-06-01

Patients and animals with diabetes exhibit enhanced vulnerability to bacterial surgical infections. Despite multiple retrospective studies demonstrating the benefits associated with glycemic control in reducing bacterial infection after cardiac surgery, there are fewer guidelines on the use of glycemic control for noncardiac surgeries. In the current study, we investigated whether long-term (begun 2 weeks before surgery) or immediate (just before surgery) glycemic controls, continued postoperatively, can reduce surgical site infection in type 1 diabetic-induced rats. Rats were injected with streptozotocin to induce type 1 diabetes. Four groups of animals underwent surgery and thigh muscle Staphylococcus aureus bacteria challenge (1 × 10 colony forming units) at the time of surgery. Group 1 diabetic rats received insulin treatment just before surgery and continued until the end of study (short-term glycemic control group). Group 2 diabetic rats received insulin treatment 2 weeks before surgery and continued until the end of study (long-term glycemic control). Group 3 diabetic rats received no insulin treatment (no glycemic control group). Group 4 nondiabetic rats served as a healthy control group. Rats were euthanized at 3 or 6 days after surgery. Blood glucose and muscle bacterial burden were measured at 3 or 6 days after surgery. Glycemic control was achieved in both long- and short-term insulin-treated diabetic rats. Compared with untreated diabetic rats, the bacterial burden in muscle was significantly lower in both groups of glycemic controlled diabetic rats at 3 (all P < 0.003) and 6 (all P < 0.0001) days after surgery. A short-term glycemic control regimen, initiated just before surgery and bacterial exposure, was as effective in reducing surgical site infection as a long-term glycemic control in type 1 diabetic rats. These data suggest that immediately implementing glycemic control in type 1 diabetic surgical patients before undergoing noncardiac surgery may decrease the risk of infection.

Can organic and transgenic soy be used as a substitute for animal protein by rats?

PubMed

Soares, L L; Lucas, A M M; Boaventura, G T

2005-04-01

We evaluated the protein quality of organic and transgenic soy fed to rats throughout life. Thirty female Wistar rats were divided into three groups (N = 10): organic soy group (OSG) receiving organic soy-based diet, genetically modified soy group (GMSG) receiving transgenic soy-based diet, and a control group (CG) receiving casein-based diet. All animals received water and isocaloric diet (10% protein), ad libitum for 291 days. After this, the weight of GMSG animals (290.9 +/- 9.1 g) was significantly lower (P <= 0.04) than CG (323.2 +/- 7.9 g). The weight of OSG (302.2 +/- 8.7 g) was between that of the GMSG and the CG. Protein intake was similar for OSG (308.4 +/- 6.8 g) and GMSG (301.5 +/- 2.5 g), and significantly lower (P <= 0.0005) than the CG (358.4 +/- 8.1 g). Growth rate was similar for all groups: OSG (0.80 +/- 0.02 g), GMSG (0.81 +/- 0.03 g) and CG (0.75 +/- 0.02 g). In addition to providing a good protein intake and inducing less weight gain, both types of soy were utilized in a manner similar to that of casein, suggesting that the protein quality of soy is similar to that of the standard protein casein. The groups fed soy-based diet gained less weight, which may be considered to be beneficial for health. We conclude that organic and transgenic soy can be fed throughout life to rats in place of animal protein, because contain high quality protein and do not cause a marked increase in body weight.

Primate paneth cell degeneration following methylmercury hydroxide ingestion.

PubMed Central

Mottet, N. K.; Body, R. L.

1976-01-01

The effects of methylmercury on the intestinal epithelium were studied in 14 adolescent male Macaca mulatta monkeys weighing 3 to 5 kg. They were divided into three groups: two controls received daily applesauce vehicle without methylmercury. Nine chronic low-dose animals received 0.2 to 1.0 mg of methylmercury per day for 80 to 491 days. Three acute high-dose animals received 2.0 mg methylmercury for 17 to 18 days, when they became terminally ill. Light and electron microscopic observations were made on samples of duodenum and ileum following perfusion and immersion fixation in a glutaraldehyde-paraformaldehyde fixative. Numerous uniquely structured inclusions were prominent in the Paneth cells of the chronic low-dose animals and some necrotic Paneth cells were seen, especially in the most chronic and higher dosed animals of the group. Acute high-dose treatment produced some inclusions in the Paneth cells similar to those of the chronic low-dose group, but degenerative and necrotic cells were more frequently seen. These alterations were not seen in other intestinal epithelial cells. Paneth cells are selectively altered. These findings suggest that a function of Paneth cells may be to eliminate metals from the body. Images Figure 11 Figure 12 Figure 13 Figure 1 Figure 2 Figure 3 Figures 4 and 5 Figure 14 Figure 15 Figures 16-18 Figures 6-10 PMID:820204

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.

PubMed

Owolabi, J O; Olatunji, S Y; Olanrewaju, A J

2017-05-01

Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters.

Connexin43 Gene Transfer Reduces Ventricular Tachycardia Susceptibility After Myocardial Infarction

PubMed Central

Greener, Ian D.; Sasano, Tetsuo; Wan, Xiaoping; Igarashi, Tomonori; Strom, Maria; Rosenbaum, David S.; Donahue, J. Kevin

2012-01-01

Objectives The aim of this study was to evaluate the links between connexin43 (Cx43) expression, myocardial conduction velocity, and ventricular tachycardia in a model of healed myocardial infarction. Background Post-infarction ventricular arrhythmias frequently cause sudden death. Impaired myocardial conduction has previously been linked to ventricular arrhythmias. Altered connexin expression is a potential source of conduction slowing identified in healed scar border tissues. The functional effect of increasing border-zone Cx43 has not been previously evaluated. Methods Twenty-five Yorkshire pigs underwent anterior infarction by transient left anterior descending coronary artery occlusion, followed by weekly testing for arrhythmia inducibility. Twenty animals with reproducibly inducible sustained monomorphic ventricular tachycardia were randomized 2:1:1 to receive AdCx43, Adβgal, or no gene transfer. One week later, animals underwent follow-up electrophysiologic study and tissue assessment for several functional and molecular measures. Results Animals receiving AdCx43 had less electrogram fractionation and faster conduction velocity in the anterior-septal border zone. Only 40% of AdCx43 animals remained inducible for ventricular tachycardia, while 100% of controls were inducible after gene transfer. AdCx43 animals had 2-fold higher Cx43 protein levels in the anterior-septal infarct border, with similar percents of phosphorylated and intercalated disk-localized Cx43 compared with controls. Conclusions These data mechanistically link Cx43 expression to slow conduction and arrhythmia susceptibility in the healed scar border zone. Targeted manipulation of Cx43 levels improved conduction velocity and reduced ventricular tachycardia susceptibility. Cx43 gene transfer represents a novel treatment strategy for post-infarction arrhythmias. PMID:22883636

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

Vikram, A.; Tripathi, D.N.; Ramarao, P.

Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells.more » The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.« less

[Strategy of comprehensive control for schistosomiasis and its effect in key areas of Jiangsu Province].

PubMed

Sun, Le-Ping; Tian, Zeng-Xi; Yang, Kun; Hong, Qing-Biao; Gao, Yang; Gao, Yuan; Zhang, Lian-Heng; Yang, Guo-Jing; Min, Jie; Ge, Jun; Wu, Hong-Hui; Huang, Yi-Xin; Liang, You-Sheng

2011-12-01

To evaluate the effect of comprehensive control for schistosomiasis in key areas of Jiangsu Province. The basic data and the data of implementation of comprehensive control measures were collected from the key areas of Jiangsu Province, including 30 townships, 87 marshlands and 78 anchor points. A field survey was carried out to investigate the Oncomelania snail status by using the systematic sampling method and schistosomiasis morbidity in humans and animals in the 12 key counties (districts). The changes of snail status and morbidity of humans and animals were statistically analyzed in key counties (districts) where comprehensive control measures was implemented, and the effects of schistosomiasis control before and after the implementation of the comprehensive control were compared. From 2008 to 2010, a total of 84 100 harmless latrines were constructed, 339 600 persons were examined, 2.6938 million people received health education, 112 000 protective creams and 798 000 publicity materials were allocated, 9 085 domestic animals were reared in pens, 11 800 domestic animals were examined, 130 high-risk cattle were eliminated in 30 key townships of 12 countries (districts), Jiangsu Province. A total of 19 640.78 hm2 were controlled with molluscicides, 798 warning tablets were placed, 116.07 hm2 of farmlands were ploughed up and planted, 306.80 hm2 were dug for fish culture, and 506.74 hm2 were planted with trees for snail control in 87 high-risk marshlands. A total of 118.83 million Yuan were invested into the water resources development projects, 39.82 km-long rivers were dredged, 70.04 km-long bank were concreted, 30 culvert gates were re-constructed, and 22 snail sedimentation tanks were built. In the 78 anchor points, 95 harmless public toilets were built, 3 192 stool container were allocated, 28 700 boatmen were examined, 71 600 protective creams and 53 200 publicity materials were allocated, and 46 600 persons received health education. Following the implementation of comprehensive control, the settings with infected snails, infected snail areas, infection rates of snails reduced from 75, 802.73 hm2 and 0.10% before the comprehensive control in 2007 to all 0 in 2010, with reduction rates of all 100%. The infection rates of schistosome in both humans and domestic animals appeared declining trends in 12 counties (districts) from 2005 to 2010, and the human infection rates were 0.16%, 0.04%, 0.02%, 0.02%, 0.01% and 0.01%, respectively, while being 0.11%, 0.05%, 0, 0, 0 and 0, respectively in domestic animals. During the period of comprehensive control, totally 45 transmission-controlled townships and 183 villages were newly added. In 2010, all of the 12 counties (districts) reached the criteria of schistosomiasis transmission control. The comprehensive control with emphasis on the key areas where infected snails are found, is an effective measure to further facilitate schistosomiasis control and rapidly control the transmission of schistosomiasis.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate.

PubMed

Kuduban, Ozan; Mazlumoglu, Muhammed Recai; Kuduban, Selma Denktas; Erhan, Ertugrul; Cetin, Nihal; Kukula, Osman; Yarali, Oguzhan; Cimen, Ferda Keskin; Cankaya, Murat

2016-01-01

To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

Biosafety of the application of biogenic nanometal powders in husbandry

NASA Astrophysics Data System (ADS)

Anatolievna Nazarova, Anna; Dmitrievna Polischuk, Svetlana; Anatolievna Stepanova, Irina; Ivanovich Churilov, Gennady; Chau Nguyen, Hoai; Buu Ngo, Quoc

2014-03-01

Effects of iron and copper nanopowders (particle size of 20-40 nm) were investigated on rabbits of 1 month age and heifers of 6 months. For introduction of nanometals into the animal's ration, the mixed fodder was treated with the nanometal powder suspension in such a way: 0.08 mg of nanoiron per kg of animal's body weight and 0.04 mg kg-1 for nanocopper. The weight gain of the heifers who received nanoiron and nanocopper after 8 months was 22.4 and 10.7% higher than that of the control, respectively. For the rabbits who received nano Fe and Cu after 3 months, the weight gain was 11.7 and 7.3% compared to the control, respectively. Under the action of metal nanopowders morphological indices of blood were changed in comparison with the control: after 8 months the quantity of erythrocytes increased by 19.6%, hemoglobin by 17.1% and leukocytes by 7.6%. There was a realignment in leukocytic formula: the quantity of lymphocytes increased by 9% compared to the control. Biogenic metals in superdispersive state were able to stimulate immune, enzymatic and humoral systems of the animal's organism, promoting metabolism. Adding Co and Cu metal nanopowders to the bull-calves’ fodder rations increased content of Ca by 31.8 and 0%, Fe by 38.8 and 37.5%, K by 19.2 and 15.3%, Mg by 17.6 and 23.5%, Mn by 9.8 and 45% and Na by 20.5 and 8.8%, respectively, compared to control. Metal nanopowders improved the quality indices and meat productivity of black-white bull-calves, expressed in intensive growth of muscle, tissue and more nutritious meat. The conducted veterinary-sanitary expertise showed that the supplements based on iron, cobalt and copper nanopowders can be used as safe bioactive supplements in animal husbandry.

Altered regulation of Nur77 nuclear receptor gene expression in the mesocorticolimbic regions of rat brain by amphetamine sensitization.

PubMed

Bhardwaj, Sanjeev K; Dodat, Fatéma; Lévesque, Daniel; Srivastava, Lalit K

2018-05-08

The mechanisms underlying psychostimulant drug-induced sensitization include long-term cellular and molecular adaptations in dopaminergic circuits. Nur77, a member of the Nur family of transcription factors, is expressed in brain regions receiving dopamine inputs and plays a role in activity-induced synaptic modification. Here we evaluated changes in Nur77 mRNA levels in the medial prefrontal cortex (mPFC), dorsal striatum (Str) and nucleus accumbens (NAc) of rats receiving a repeated, sensitizing regimen of amphetamine (AMPH). Results were compared to two groups of controls - animals receiving repeated injections of saline (Rp-SAL) or with no treatment (CON). Two weeks after the last injection, the effect of an acute challenge dose of AMPH on Nur77 expression was evaluated using in-situ hybridization. Repeated AMPH treatment (Rp-AMPH) increased the levels of Nur77 mRNA in the mPFC, NAc core and shell regions. However, the effects of an acute injection of AMPH in each of the three groups of animals was distinct. Whereas an acute AMPH led to a significant increase of Nur77 in all brain regions of the CON animals, it had no significant effect in Rp-SAL animals. Interestingly, in acute AMPH-injected Rp-AMPH animals, Nur77 mRNA levels in the mPFC, Str and NAc regions were significantly lower compared to CON and Rp-SAL animals treated with acute AMPH. There was a positive correlation between AMPH -induced locomotor activity and Nur77 mRNA expression in CON animals; however, this relationship was absent in Rp-SAL and Rp-AMPH animals. The data suggest that Nur77 is a part of neuroadaptive changes caused by either mild stress of repeated injections as well as AMPH-sensitization and may play a role in abnormal behaviors induced by the drug. Copyright © 2018. Published by Elsevier B.V.

Changes in behavioural parameters, oxidative stress and neurotrophins in the brain of adult offspring induced to an animal model of schizophrenia: The effects of FA deficient or FA supplemented diet during the neurodevelopmental phase.

PubMed

Canever, L; Freire, T G; Mastella, G A; Damázio, L; Gomes, S; Fachim, I; Michels, C; Carvalho, G; Godói, A K; Peterle, B R; Gava, F F; Valvassori, S S; Budni, J; Quevedo, J; Zugno, A I

2018-05-18

A deficiency of maternal folic acid (FA) can compromise the function and development of the brain, and may produce a susceptibility to diseases such as schizophrenia (SZ) in the later life of offspring. The aim of this study was to evaluate the effects of both FA deficient and FA supplemented diets during gestation and lactation on behavioural parameters, the markers of oxidative stress and neurotrophic factors in adult offspring which had been subjected to an animal model of SZ. Female mother rats (Dam's) were separated into experimental maternal groups, which began receiving a special diet (food) consisting of the AIN-93 diet, a control diet, or an FA deficient diet during the periods of pregnancy and lactation. Dam's receiving the control diet were further subdivided into four groups: one group received only control diet, while three groups to receive supplementation with FA at different doses (5, 10 and 50 mg/kg). Adult offspring bred from the Dam's were divided into ten groups for induction of the animal model of SZ through the administration of ketamine (Ket) (25 mg/kg). After the last administration of the drug, the animals were subjected to the behavioural tests and were then euthanized. The frontal cortex (FC) and hippocampus (Hip) were then dissected for later biochemical analysis. Our data demonstrates that Ket induced the model of SZ by altering the behavioural parameters (e.g. hyperlocomotion, social impairment, deficits in the sensory-motor profile and memory damage in the adult animals); and also caused changes in the parameters of oxidative stress (lipid hydroperoxide - LPO; 8-isoprostane - 8-ISO; 4-hydroxynonenal - 4-HNE; protein carbonyl content; superoxide dismutase - SOD and catalase - CAT) as well as in the levels of neurotrophic factors (brain-derived neurotrophic factor - BDNF and nerve growth factor - NGF) particularly within the FC of adult offspring. A deficiency in maternal FA, alone or in combination with ket, was able to induce hyperlocomotion and social impairment in the offspring with increased levels of lipid and protein damage (LPO, 8-ISO, 4-HNE, carbonylation of protein) within the FC, increased activity of antioxidant enzymes (SOD and CAT) in both of the brain structures studied, and also reduced the levels of neurotrophins (BDNF and NGF), particularly within the Hip of the adult offspring. Supplementation of FA (5, 10 and 50 mg/kg) to the Dam's was mostly able to prevent the cognitive damage which was induced by Ket in the adult animals. FA (10 and 50 mg/kg) attenuated the action of Ket in the animals in relation to the biochemical parameters, proving the possible neuroprotective effect of FA in the adulthood of offspring that were subjected to the animal model of SZ. Our study indicates that the intake of maternal FA during pregnancy and lactation plays an important role, particularly in the regulation of markers of oxidative stress and neurotrophins. Copyright © 2018 Elsevier Inc. All rights reserved.

In vivo degradation of a new concept of magnesium-based rivet-screws in the minipig mandibular bone.

PubMed

Schaller, Benoit; Saulacic, Nikola; Beck, Stefan; Imwinkelried, Thomas; Goh, Bee Tin; Nakahara, Ken; Hofstetter, Willy; Iizuka, Tateyuki

2016-12-01

Self-tapping of magnesium screws in hard bone may be a challenge due to the limited torsional strength of magnesium alloys in comparison with titanium. To avoid screw failure upon implantation, the new concept of a rivet-screw was applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside were expanded inside drill holes of minipig mandibles. During the expansion with a hexagonal mandrel, the threads engaged the surrounding bone and the inside of the screw transformed into a hexagonal screw drive to allow further screwing in or out of the implant. The in vivo degradation of the magnesium implants and the performance of the used coating were studied in a human standard-sized animal model. Four magnesium alloy rivet-screws were implanted in each mandible of 12 minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy implants; another six received the uncoated magnesium alloy rivet-screws. Two further animals received one titanium rivet-screw each as control. In vivo radiologic examination was performed at one, four, and eight weeks. Euthanasia was performed for one group of seven animals (three animals with coated, three with uncoated magnesium alloy implants and one with titanium implant) at 12weeks and for the remaining seven animals at 24weeks. After euthanasia, micro-computed tomography and histological examination with histomorphometry were performed. Significantly less void formation as well as higher bone volume density (BV/TV) and bone-implant contact area (BIC) were measured around the coated implants compared to the uncoated ones. The surface coating was effective in delaying degradation despite plastic deformation. The results showed potential for further development of magnesium hollow coated screws for bone fixation. Copyright © 2016 Elsevier B.V. All rights reserved.

Altered cytokeratin expression during chemoprevention of experimental hamster buccal pouch carcinogenesis by garlic.

PubMed

Balasenthil, S; Rao, K S; Nagini, S

2002-03-01

Cytokeratins (also known as keratins (K)) are members of the family of intermediate filaments and form major components of the mammalian epithelial cell cytoskeleton. Cytokeratins have emerged as reliable cellular markers of oral cancer development and chemoprevention because of their abundance, stability and high antigenicity. We investigated the effect of aqueous garlic extract on cytokeratin expression during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin, on the right buccal pouches, three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group 1 and also received 250 mg/kg body weight aqueous garlic extract orally on alternate days to the DMBA application. Group 3 animals received garlic extract only, as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The hamsters were killed after an experimental period of 14 weeks. Cytokeratin expression was studied using human monoclonal antibodies AE1 and AE3, which react with type I and II keratins. In DMBA-induced squamous cell carcinomas, decreased expression of high molecular weight keratins was observed. Administration of garlic extract to animals painted with DMBA suppressed HBP carcinomas and restored normal cytokeratin expression. The results of the present study suggest that inhibition of HBP carcinogenesis by garlic may be due to its regulatory effects on differentiation, tumour invasiveness, migratory and metastatic potential. We suggest that one of the mechanisms of tumour inhibition by garlic is an influence on cellular differentiation.

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

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

PubMed

Gadad, Bharathi S; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P; Marti, C Nathan; Young, Keith; Hewitson, Laura; German, Dwight C

2015-10-06

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

PubMed Central

Gadad, Bharathi S.; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P.; Marti, C. Nathan; Young, Keith; Hewitson, Laura; German, Dwight C.

2015-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD. PMID:26417083

Effect of Schizandra chinensis lignans on cell division in the corneal epithelium and tongue of albino rats exposed to chronic cold stress

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

Mel'nik, E.I.; Lupandin, A.V.; Timoshin, S.S.

The authors study the possibility of correcting cellular manifestations of disadaptation following chronic exposure to cold stress by means of preparations of Sch. chinensis. The model of chronic stress was cooling male albino rats daily for 1.5 h to a temperature of 28-30 C for 28 days. Since differences between levels of proliferation in intact animals and in the rats receiving 1.9% ethanol solution were absent, values obtained in the group of intact animals are presented in a table as the control. The animals underwent euthanasia 48 hours after the final exposure to the cold. The rats received an injectionmore » of tritium-thymidine one hour before sacrifice. It is shown that the results confirm those in previous studies of stimulation of DNA synthesis and mitotic activity in the corneal and lingual epithelium of albino rats during chronic exposure to stress.« less

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

PubMed

Kashani, Masoud Soheili; Tavirani, Mostafa Rezaei; Talaei, Sayyed Alireza; Salami, Mahmoud

2011-04-01

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 μg Aβ1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. The lavender extract can effectively reverse spatial learning deficits in AD rats.

Effects of ovariectomy and estrogen replacement therapy on laryngeal tissue: a histopathological experimental animal study.

PubMed

Tatlipinar, Arzu; Günes, Pembegül; Ozbeyli, Dilek; Cimen, Burak; Gökçeer, Tanju

2011-12-01

To determine the histopathological effect of estrogen deficiency and hormone replacement treatment on laryngeal tissue in ovariectomized rats. Animal study. The study was conducted at the animal experiment laboratory of Marmara University School of Medicine, Istanbul, Turkey. Six-month-old female Wistar albino rats were divided into the following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and ovariectomized with estrogen replacement. Rats in the ovariectomized with estrogen replacement group received 17 β-estradiol valerate (200 µg/kg, subcutaneously) once a week. Animals were killed after 8 weeks of intervention. Significant changes were observed in the ovariectomized group when edema in lamina propria, inflammation in squamous, respiratory epithelia and lamina propria, pseudostratification, and cilia loss were assessed. Except cilia loss, there were no significant differences in the assessments between the sham-operated control and ovariectomized with estrogen replacement groups. On the basis of histopathological evaluations, it was shown that estrogen replacement helped to improve laryngeal changes due to experimentally induced menopause.

Systemic cell-mediated reactions in vivo. Effect of the interaction of circulating antigen with sensitized lymphocytes on glomeruli and pulmonary alveoli.

PubMed Central

Bhan, A. K.; Schneeberger, E. E.; Collins, A. B.; McCluskey, R. T.

1984-01-01

The effects of systemic cell-mediated hypersensitivity reactions on glomeruli and lungs were investigated in rats. The animals were given an intravenous injection of antigen 7 days after sensitization or were given an intravenous injection of lymph node cells from sensitized syngeneic donors 1 day after antigen injection. Control animals were given an irrelevant antigen or saline. All animals received three injections of 3H-thymidine during the course of the experiments. The animals were sacrificed 2 or 3 days after antigen injection. Autoradiographs of renal and pulmonary tissue showed significantly more labeled mononuclear cells in glomeruli and pulmonary alveolar walls in the experimental groups than in the control groups. Immunofluorescence studies did not reveal antigen, rat IgG, or C3 in glomeruli. The results indicate that systemic cell-mediated reactions can lead to an accumulation of mononuclear cells in glomeruli and lungs, an effect that may contribute to tissue injury. Images Figure 1 Figure 2 Figure 3 PMID:6611090

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

PubMed

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

2016-03-01

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

Effects of thalidomide on DMBA-induced oral carcinogenesis in hamster with respect to angiogenesis.

PubMed

Yang, Y; Ge, J-P; Zhou, Z-T

2009-05-01

Thalidomide has been shown to have anti-angiogenic effects in pre-clinical models as well as a significant antitumor effect in hematologic tumors. However, the effects of thalidomide on oral pre-malignant lesions and oral carcinogenesis remain unexplored. The authors aimed to investigate the chemopreventive effect of thalidomide on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis. Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in group A and B, while animals in group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in group B and D received thalidomide daily (40 mg/kg body weight/day) by gavage, animals in group A and C received same volume of saline. Animals in group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for examinations. Thalidomide significantly decreased the squamous cell carcinoma (SCC) incidence from 57.9 to 11.8%; angiogenesis was inhibited in dysplasia and SCC. The gene expression of vascular endothelium growth factor and tumor necrosis factor (TNF)-alpha was downregulated. Thalidomide has inhibitory effect against the malignant transformation of oral pre-cancerous lesion and angiogenesis during oral carcinogenesis. Such inhibition is related to its modulation of TNF-alpha.

Establishment of a New Zealand rabbit model of spinal tuberculosis.

PubMed

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

2015-04-01

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

Effect of Erythropoietin on Postresuscitation Renal Function in a Swine Model of Ventricular Fibrillation.

PubMed

Pantazopoulos, Charalampos; Iacovidou, Nicoletta; Kouskouni, Evangelia; Pliatsika, Paraskevi; Papalois, Apostolos; Kaparos, Georgios; Barouxis, Dimitrios; Vasileiou, Panagiotis; Lelovas, Pavlos; Kotsilianou, Olympia; Pantazopoulos, Ioannis; Gkiokas, Georgios; Garosa, Clara; Faa, Gavino; Xanthos, Theodoros

2016-01-01

Purpose . To investigate the effect of EPO administration on postresuscitation renal function. Methods . Twenty-four female Landrace/Large-White piglets aged 10-15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results . Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC ( p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI ( p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions . Administration of EPO protected swine from postresuscitation acute kidney injury.

Effect of Erythropoietin on Postresuscitation Renal Function in a Swine Model of Ventricular Fibrillation

PubMed Central

Kouskouni, Evangelia; Pliatsika, Paraskevi; Kaparos, Georgios; Barouxis, Dimitrios; Lelovas, Pavlos; Kotsilianou, Olympia; Pantazopoulos, Ioannis; Gkiokas, Georgios; Garosa, Clara

2016-01-01

Purpose. To investigate the effect of EPO administration on postresuscitation renal function. Methods. Twenty-four female Landrace/Large-White piglets aged 10–15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results. Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC (p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI (p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions. Administration of EPO protected swine from postresuscitation acute kidney injury. PMID:27847811

Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs.

PubMed

Favarato, E S; Souza, M V; Costa, P R S; Favarato, L S C; Nehme, R C; Monteiro, B S; Bonfá, L P

2012-08-01

This research aimed to evaluate the effect of metoclopramide and ranitidine in the prevention of gastroesophageal reflux episodes during anesthetic procedures. Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy, randomly divided into three groups of 30 animals. The control group received only the anesthetic protocol. The metoclopramide group received an intravenous bolus of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after anesthetic induction. The ranitidine group received an intravenous bolus of 2 mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane) was standardized and the esophageal pH variations were recorded. Esophagoscopy was carried out after surgery. No difference (p<0.05) was verified in the reflux episodes between the groups. Seven animals presented reflux. Metoclopramide in bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did not influence the reduction of the incidence of gastroesophageal reflux. Copyright © 2011 Elsevier Ltd. All rights reserved.

9 CFR 304.3 - Conditions for receiving inspection.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Conditions for receiving inspection. 304.3 Section 304.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION APPLICATION...

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model.

PubMed

Camacho-Alonso, Fabio; López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-05-01

The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. The administration of bisphosphonates increases the fracture resistance in mandible and femur.

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

NASA Astrophysics Data System (ADS)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

Schinus terebinthifolius Raddi (Anacardiaceae) in the healing process of gastrorraphy in rats.

PubMed

dos Santos, Orlando José; Barros-Filho, Allan Kardec Duailibe; Malafaia, Osvaldo; Ribas-Filho, Jurandir Marcondes; Santos, Rayan Haquim Pinheiro; Santos, Rennan Abud Pinheiro

2012-01-01

Gastrorraphy, isolated or associated with the use of biological adhesives, was throughout the history of surgery the usual way to promote healing in gastric lesions and the use of herbal medicine has been increasingly more employed. To evaluate the wound healing in the stomach of rats with the use of the hydroalcoholic extract of Schinus terebinthifolius Raddi (aroeira). Sixty rats, adult males, were divided into two groups: aroeira group and control group. Each one was subdivided into four subgroups of 15 animals (test groups). Each subdivided subgroup was also subdivided into three subgroups of five rats (deaths periods of 7, 14 and 21 days). All animals underwent the same surgical procedure (injury and stomach suture); animals in the aroeira group received daily dose of 100 mg/kg of hydroalcoholic extract via gavage while the control group received isotonic saline solution. Parameters evaluated were: macroscopic and microscopic changes, test for resistance to insufflation of atmospheric air and test for tensile strength. All animals had good healing of the abdominal wall and gastrorraphies without infection and dehiscence. Both groups had adhesions to the gastrorraphies surfaces with neighboring organs. The resistance test by insufflation of atmospheric air and tensile strength showed higher average of pressure on the 7th day and breaking strength in the time periods for the aroeira group. The intensity of chronic inflammation revealed statistically significant differences in the variables fibroblast proliferation and collagen. The use of hydroalcoholic extract of Schinus terebinthifolius Raddi accelerated the stomach healing in rats.

Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

PubMed

Ho, Y C; Wang, S

2010-11-24

Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

THE RELATIONSHIP BETWEEN BOTH REAL-TIME AND TIME-INTEGRATED COARSE AND FINE PARTICULATE MATTER AT AN URBAN SITE IN LOS ANGELES

EPA Science Inventory

Population exposure to ambient particulate matter (PM) has received considerable attention due to the association between ambient particulate concentrations and mortality. Current toxicological studies and controlled human and animal exposures suggest that all size fractions of...

Controlled Cortical Impact in Swine: Pathophysiology and Biomechanics

DTIC Science & Technology

2005-03-28

et al 3/28/05 free access to food and water until 12 h before anesthesia was induced. After intubation, anesthesia was maintained with a fentanyl ...injury in 10 of these 13 animals. Histological Studies After completion of monitoring, the swine received an overdose of pentobarbital. The brain was

78 FR 64908 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

...-APHIS- VS Agreement for Handling Restricted Imports of Animal By-Products and Controlled Materials (VS... By-Products, and Other Material (VS Form 16-78); USDA-APHIS-VS Application for Import or in Transit.... Comments regarding this information collection received by November 29, 2013 will be considered. Written...

Noninvasive control of rhodamine-loaded capsules distribution in vivo

NASA Astrophysics Data System (ADS)

Stelmashchuk, O.; Tarakanchikova, Y.; Seryogina, E.; Piavchenko, G.; Zherebtsov, E.; Dunaev, A.; Popov, A.; Meglinski, I.

2018-04-01

Using fluorescence spectroscopy system with fibre-optical probe, we investigated the dynamics of propagation and circulation in the microcirculatory system of experimental nanocapsules fluorescent-labelled (rhodamine TRITC) nanocapsules. The studies were carried out in clinically healthy Wistar rats. The model animals were divided into control group and group received injections of the nanocapsules. The fluorescent measurements conducted transcutaneously on the thigh surface. The administration of the preparation with the rhodamine concentration of 5 mg/kg of animal weight resulted in twofold increase of fluorescence intensity by reference to the baseline level. As a result of the study, it was concluded that fluorescence spectroscopy can be used for transdermal measurements of the rhodamine-loaded capsules in vivo.

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

PubMed

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

2011-02-01

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

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.

Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

PubMed

Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

2013-01-01

Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p < 0.001). RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p < 0.001). RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model

PubMed Central

López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-01-01

Objective: The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. Study design: A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). Results: A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. Conclusions: The administration of bisphosphonates increases the fracture resistance in mandible and femur. Key words:Zoledronic acid, bisphosphonates, animal experimentation, fracture test. PMID:23524420

Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

USGS Publications Warehouse

Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.

2007-01-01

This report presents environmental and quality-control data from analyses of 15 pharmaceutical and 31 antibiotic compounds in water samples from streams and wells in south-central Pennsylvania. The analyses are part of a study by the U.S. Geological Survey (USGS) in cooperation with the Pennsylvania Department of Environmental Protection (PADEP) to define concentrations of selected emerging contaminants in streams and well water in Pennsylvania. Sampling was conducted at 11 stream sites and at 6 wells in 9 counties of south-central Pennsylvania. Five of the streams received municipal wastewater and 6 of the streams received runoff from agricultural areas dominated by animal-feeding operations. For all 11 streams, samples were collected at locations upstream and downstream of the municipal effluents or animal-feeding operations. All six wells were in agricultural settings. A total of 120 environmental samples and 21 quality-control samples were analyzed for the study. Samples were collected at each site in March/April, May, July, and September 2006 to obtain information on changes in concentration that could be related to seasonal use of compounds.For streams, 13 pharmaceuticals and 11 antibiotics were detected at least 1 time. Detections included analytical results that were estimated or above the minimum reporting limits. Seventy-eight percent of all detections were analyzed in samples collected downstream from municipal-wastewater effluents. For streams receiving wastewater effluents, the pharmaceuticals caffeine and para-xanthine (a degradation product of caffeine) had the greatest concentrations, 4.75 μg/L (micrograms per liter) and 0.853 μg/L, respectively. Other pharmaceuticals and their respective maximum concentrations were carbamazepine (0.516 μg/L) and ibuprofen (0.277 μg/L). For streams receiving wastewater effluents, the antibiotic azithromycin had the greatest concentration (1.65 μg/L), followed by sulfamethoxazole (1.34 μg/L), ofloxacin (0.329 μg/L), and trimethoprim (0.256 μg/L).For streams receiving runoff from animal-feeding operations, the only pharmaceuticals detected were acetaminophen, caffeine, cotinine, diphenhydramine, and carbamazepine. The maximum concentration for pharmaceuticals was 0.053 μg/L. Three streams receiving runoff from animal-feeding operations had detections of one or more antibiotic compound--oxytetracycline, sulfadimethoxine, sulfamethoxazole, and tylosin. The maximum concentration for antibiotics was 0.157 μg/L. The average number of compounds (pharmaceuticals and antibiotics) detected in sites downstream from animal-feeding operations was three. The average number of compounds detected downstream from municipal-wastewater effluents was 13.For wells used to supply livestock, four compounds were detected--two pharmaceuticals (cotinine and diphenhydramine) and two antibiotics (tylosin and sulfamethoxazole). There were five detections in all the well samples. The maximum concentration detected in well water was for cotinine, estimated to be 0.024 μg/L.Seasonal occurrence of pharmaceutical and antibiotic compounds in stream water varied by compound and site type. At four stream sites, the same compounds were detected in all four seasonal samples. At other sites, pharmaceutical or antibiotic compounds were detected only one time in seasonal samples. Winter samples collected in streams receiving municipalwastewater effluent had the greatest number of compounds detected (21). Research analytical methods were used to determine concentrations for pharmaceuticals and antibiotics. To assist in evaluating the quality of the analyses, detailed information is presented on laboratory methodology and results from qualitycontrol samples. Quality-control data include results for nine blanks, nine duplicate environmental sample pairs, and three laboratory-spiked environmental samples as well as the recoveries of compounds in laboratory surrogates and laboratory reagent spikes.

The Manufacture, Shipping and Receiving and Quality Control of Rodent Bedding Materials

NASA Technical Reports Server (NTRS)

Kraft, Lisbeth M.

1980-01-01

The criteria for rodent bedding and nesting materials are discussed. The literature is reviewed regarding sources of bedding materials, manufacturing methods, quality control, procedures (microbiological, physical and chemical), storage, methods, shipment, methods of use and disposal, current knowledge concerning bedding effects on animals as related to research and testing and legal aspects. Future needs, especially with respect to the promulgation of standards, also are addressed.

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

PubMed

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

2015-01-01

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

Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi

2015-01-01

Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g) were randomized into four groups (I–IV). Group I (control) received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats. PMID:29051470

High doses of nandrolone decanoate reduce volume of testis and length of seminiferous tubules in rats.

PubMed

Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah

2005-02-01

Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Hemi-Facial Allotransplantation Model

PubMed Central

Goto, Shigeru; Huang, Yu-Ting; Wang, Chun-Ting; Tsai, Chia-Chun; Chen, Chao-Long

2012-01-01

Background In this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model. Methodology/Principal Findings Outbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days −1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days −1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3+T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups. Conclusions These results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression. PMID:22558153

Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model.

PubMed

Jain, Nikhil; Himed, Khaled; Toth, Jeffrey M; Briley, Karen C; Phillips, Frank M; Khan, Safdar N

2018-04-19

Opioid use is prevalent for management of pre- and post-operative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in-vitro, and one previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. To study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. Pre-clinical animal study. 24 adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received four-weeks pre-operative and six-weeks post-operative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and four-weeks post-operatively to ensure adequate levels. The control group (n=12) received only peri-operative pain control as necessary. All animals received a bilateral L5-L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the six-week post-operative time point, and assessment of fusion was done by manual palpation, plain radiographs, micro-computed tomography (microCT), and histology. 12 animals in control group and 11 animals in the opioid group were available for analysis at the end of six weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=0.09), lower trabecular number (p=0.02) and higher trabecular separation (p=0.02) as compared to control. Histological analysis found areas of incorporation of autograft, and unincorporated graft fragments in both groups. In the control group, there was remodeling of de-novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de-novo woven bone, and hypertrophied osteoblasts seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histological findings of relatively immature fusion mass in the opioid group. Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at six-weeks in this rabbit spinal fusion model. These preliminary results lay foundation for further research to investigate underlying cellular mechanisms, temporal fusion process, and dose-duration relationship of opioids responsible for our findings. Copyright © 2018 Elsevier Inc. All rights reserved.

Randomized clinical trial to evaluate the efficacy of a 5-day ceftiofur hydrochloride intramammary treatment on nonsevere gram-negative clinical mastitis.

PubMed

Schukken, Y H; Bennett, G J; Zurakowski, M J; Sharkey, H L; Rauch, B J; Thomas, M J; Ceglowski, B; Saltman, R L; Belomestnykh, N; Zadoks, R N

2011-12-01

The objective of this study was to evaluate the efficacy of intramammary treatment with ceftiofur hydrochloride of nonsevere, clinical coliform mastitis. One hundred four cases on 5 farms met the enrollment criteria for the study. Escherichia coli was the most common coliform species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Klebsiella spp. and Enterobacter spp. At enrollment, a milk sample from the affected quarter was taken and used for on-farm culture or submitted to the laboratory. For cows in the treatment group, treatment was initiated with ceftiofur hydrochloride via intramammary infusion at 24-h intervals for 5 d according to label standards. Cows in the control group did not receive treatment. Culture results were available on the day after enrollment and only cows with coliform mastitis continued in the treatment and untreated control groups. Bacteriological cure was defined based on 2 posttreatment milk samples. Molecular typing was used for final definition of bacteriological cure. Treatment of nonsevere clinical gram-negative mastitis with ceftiofur hydrochloride resulted in a significant increase in bacteriological cure compared with nontreated controls in animals infected with E. coli or Klebsiella spp. Treated animals clinically improved significantly more compared with control cows. No significant differences were observed between treated and control animals in milk production or linear score before or after clinical mastitis. Treated animals left the study less frequently compared with control animals. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Polyethylene glycol-induced motor recovery after total spinal transection in rats.

PubMed

Ren, Shuai; Liu, Ze-Han; Wu, Qiong; Fu, Kuang; Wu, Jun; Hou, Li-Ting; Li, Ming; Zhao, Xin; Miao, Qing; Zhao, Yun-Long; Wang, Sheng-Yu; Xue, Yan; Xue, Zhen; Guo, Ya-Shan; Canavero, Sergio; Ren, Xiao-Ping

2017-08-01

Despite more than a century of research, spinal paralysis remains untreatable via biological means. A new understanding of spinal cord physiology and the introduction of membrane fusogens have provided new hope that a biological cure may soon become available. However, proof is needed from adequately powered animal studies. Two groups of rats (n=9, study group, n=6 controls) were submitted to complete transection of the dorsal cord at T10. The animals were randomized to receive either saline or polyethylene glycol (PEG) in situ. After 4 weeks, the treated group had recovered ambulation vs none in the control group (BBB scores; P=.0145). One control died. All animals were studied with somatosensory-evoked potentials (SSEP) and diffusion tensor imaging (DTI). SSEP recovered postoperatively only in PEG-treated rats. At study end, DTI showed disappearance of the transection gap in the treated animals vs an enduring gap in controls (fractional anisotropy/FA at level: P=.0008). We show for the first time in an adequately powered study that the paralysis attendant to a complete transection of the spinal cord can be reversed. This opens the path to a severance-reapposition cure of spinal paralysis, in which the injured segment is excised and the two stumps approximated after vertebrectomy/diskectomies. © 2017 John Wiley & Sons Ltd.

Choline and Fructooligosaccharide: Non-alcoholic Fatty Liver Disease, Cardiac Fat Deposition, and Oxidative Stress Markers

PubMed Central

Borges Haubert, Nadia Juliana Beraldo Goulart; Marchini, Julio Sergio; Carvalho Cunha, Selma Freire; Suen, Vivian Marques Miguel; Padovan, Gilberto Joao; Jordao, Alceu Afonso; Marchini Alves, Claudia Maria Meirelles; Marchini, Julio Flavio Meirelles; Vannucchi, Helio

2015-01-01

This study investigates the treatment of non-alcoholic fatty liver disease (NAFLD) in rats with choline and fructooligosaccharide (FOS). The healthy control group received standard diet. The other three groups consisted of animals with NAFLD. Group Estr received standard diet; group Echo received standard diet plus choline (3 g/100 g diet); and group Efos received standard diet plus FOS (10 g/100 g diet). Food intake, weight, urinary nitrogen, urinary ammonia, total cholesterol, serum triacylglyceride, liver and heart weights, tissue nitrogen, tissue fat, vitamin E, TBARS, and reduced glutathione (GSH) were measured in hepatic and heart tissue. Choline and FOS treatments resulted in total mean fat reduction in liver and heart tissue of 0.2 and 1.7 g, respectively. Both treatments were equally effective in reducing hepatic and cardiac steatosis. There were no differences in the TBARS level among experimental and control groups, indicating that the proposed treatments had no added protection against free radicals. While all experimental groups had increased vitamin E and GSH levels, choline treatment led to a significant increase compared to control. PMID:25987847

Effectiveness of a short-term treatment with progesterone injections on synchrony of lambing and fertility in tropical hair sheep.

PubMed

Knights, Marlon; Ramgattie, Reeza; Siew, Narendra; Singh-Knights, Doolarie; Bourne, Gregory

2011-06-01

The efficacy of using a low cost system for delivering progesterone as part of an estrous synchronization protocol in sheep was evaluated. In experiment 1, Barbados Black Belly ewes (n=34) and ewe lambs (n=35; 37.5±0.9 kg) were assigned to be untreated, control animals (C), or to receive PGF(2α) on d0 (PG), or receive two injections of progesterone (200mg, i.m. each) on D -5 and on D -2.5, prior to PGF(2α), on D 0 (2PPG). Treatment with 2PPG increased the proportion of animals lambing to the first service (P<0.05), an effect that was greater in ewe lambs than ewes (treatment × parity; P<0.05). The interval from ram introduction to lambing and the mean lambing day was less (P=0.04) in the 2PPG-treated animals compared to control animals. In Experiment 2, lactating ewes from experiment 1 (n=61) 60-85 days postpartum were assigned within parity and number of lambs reared to remain nursing (S; n=29) or weaned (W; n=32) 3 weeks prior to treatment with the 2PPG protocol. There was no effect of treatment on the proportion of animals lambing to the first service or overall, interval from ram introduction to lambing and lambing interval. An 8-month lambing interval was observed in ewes in which estrus was synchronized regardless of physiological state. In conclusion, the two-progesterone injection synchronization protocol may be used as a practical low cost and efficient method of synchronizing estrus to reduce the lambing interval and maximize productivity in tropical breeds of sheep. Copyright © 2011 Elsevier B.V. All rights reserved.

Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity.

PubMed

Luz, Matthias; Allen, Philip C; Bringas, John; Boiko, Chris; Stockinger, Diane E; Nikula, Kristen J; Lewis, Owen; Woolley, Max; Fibiger, H Christian; Bankiewicz, Krystof; Mohr, Erich

2018-05-22

Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions. Here we present the results of a 9-month toxicity study in which rhesus monkeys received intermittent intraputamenal infusions via convection-enhanced delivery. Animals were treated with GDNF (87.1 µg; N = 14) or vehicle (N = 6) once every 4 weeks for a total of 40 weeks (11 treatments). Four of the GDNF-treated animals were utilized in a satellite study assessing the impact of concomitant catheter repositioning prior to treatment. In the main study, eight animals (5 GDNF, 3 control) were euthanized at the end of the treatment period, along with the four satellite study animals, while the remaining eight animals (5 GDNF, 3 control) were euthanized at the end of a 12-week recovery period. There were no GDNF-related adverse effects and in particular, no GDNF-related microscopic findings in the brain, spinal cord, dorsal root ganglia, or trigeminal ganglia. Therefore, 87.1 µg/4 weeks is considered the no observed adverse effect level for GDNF in rhesus monkeys receiving intermittent, convection-enhanced delivery of GDNF for 9 months.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Quantitative changes in endogenous DNA adducts correlate with conazole in vivo mutagenicity and tumorigenicity.

PubMed

Ross, Jeffrey A; Leavitt, Sharon A; Schmid, Judith E; Nelson, Garret B

2012-09-01

The mouse liver tumorigenic conazole fungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue™ transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil was not mutagenic. DNA sequencing of the mutants recovered from each treatment group as well as from animals receiving control diet revealed that propiconazole- and triadimefon-induced mutations do not represent general clonal expansion of background mutations, and support the hypothesis that they arise from the accumulation of endogenous reactive metabolic intermediates within the liver in vivo. We therefore measured the spectra of endogenous DNA adducts in the livers of mice from these studies to determine if there were quantitative or qualitative differences between mice receiving tumorigenic or nontumorigenic conazoles compared to concurrent control animals. We resolved and quantitated 16 individual adduct spots by (32)P postlabelling and thin layer chromatography using three solvent systems. Qualitatively, we observed the same DNA adducts in control mice as in mice receiving conazoles. However, the 13 adducts with the highest chromatographic mobility were, as a group, present at significantly higher amounts in the livers of mice treated with propiconazole and triadimefon than in their concurrent controls, whereas this same group of DNA adducts in the myclobutanil-treated mice was not different from controls. This same group of endogenous adducts were significantly correlated with mutant frequency across all treatment groups (P = 0.002), as were total endogenous DNA adduct levels (P = 0.005). We hypothesise that this treatment-related increase in endogenous DNA adducts, together with concomitant increases in cell proliferation previously reported to be induced by conazoles, explain the observed increased in vivo mutation frequencies previously reported to be induced by treatment with propiconazole and triadimefon.

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

PubMed

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

1987-01-01

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

Ultrastructural liver changes in the experimental thyrotoxicosis.

PubMed

Pasyechko, Nadiya Vasylivna; Kuleshko, Iryna Ihorivna; Kulchinska, Veronika Mykolaiivna; Naumova, Liudmyla Valeriivna; Smachylo, Iryna Volodymyrivna; Bob, Anzhela Olehivna; Radetska, Liudmyla Volodymyrivna; Havryliuk, Mykhailo Yevhenovych; Sopel, Olha Mykolaiivna; Mazur, Liudmyla Petrivna

Aim of the study is to evaluate ultrastructural changes of rat liver in experimental thyrotoxicosis. For the study, 36 male rats have been utilized, weighing approximately 150-190 g, which were divided into three groups: the first, control group (12 animals) was composed of healthy rats that received intragastric sodium chloride 0.9% solution, the second group (12 animals) - animals with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 2 weeks, and the third group (12 animals) - rats with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 4 weeks. For electron-microscopic studies small pieces of liver tissue were taken at the end of the 2nd and 4th weeks of the experiment. The material was studied and documented in electron micrographs by using a TEM-125K electron microscope. In experiment in white male rats the electron-microscopic state of the liver in thyrotoxicosis has been studied. It has been established that thyrotoxicosis is accompanied by the significant changes of the hepatocytes ultrastructure, blood and bile capillaries. Experimental thyrotoxicosis causes significant damage of the liver plasma membranes and intracellular structural components of hepatocytes and endothelial cells. In experimental thyrotoxicosis, on the background of microcirculatory disorders, significant damage of plasmatic and intracellular organoid membranes of hepatocytes in the liver develops, which has an adverse effect on the functionality of the organ. The found ultrastructural changes are aggravated depending on the duration of thyrotoxicosis.

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.

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

PubMed

Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

2009-02-01

This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats

PubMed Central

Owolabi, J.O.; Olatunji, S.Y.; Olanrewaju, A.J.

2017-01-01

Background Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. Purpose The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. Methods A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. Results GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals’ brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Conclusion Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters. PMID:28588361

[Efficacy of the administration of serum amd vaccine for the antirabies treatment of experimentally-infected sheep].

PubMed

Soria Baltazar, R; Blancou, J

1995-09-01

The objectives of this study were to examine the humoral immune response of sheep to experimental infection with an isolate of rabies virus from a fox, to analyse the efficacy of vaccination as a method of post-infection treatment, and to find a suitable animal model to evaluate new procedures for human vaccination following infection. A total of 47 sheep were used. Initially, 26 sheep received an intramuscular injection of a suspension of virus (titre: 10(6.8) 50% lethal dose for mice by the intracerebral route). Half of the sheep were subsequently treated using a vaccine on the day of infection and at 3, 7, 14 and 30 days post-infection. The remaining half comprised the unvaccinated controls. This vaccination protected seven of thirteen sheep, while nine of the thirteen controls died. Subsequently, 21 sheep were inoculated under the same conditions as in the previous trial. The animals were divided into three groups of seven animals each. The first group was vaccinated in the same way as described above. The second group received an injection of anti-rabies immunoglobulin of human origin (26.3 IU/kg of body weight), followed by the course of vaccine treatment 24 hours later. The remaining group acted as unvaccinated controls. Of the seven sheep given vaccine alone, four were protected, while all seven animals given immunoglobulin and vaccine were protected. Six of the seven untreated controls died. In this study, no apparently-healthy carriers of rabies virus were created by any of the treatments used, nor was there any shortening of the incubation periods. Additional observations were made concerning incubation periods and the course of the disease, as well as symptoms, lesions and the presence of rabies virus in various nerve centres and salivary glands of the experimental sheep.

Mumijo attenuates chemically induced inflammatory pain in mice.

PubMed

Malekzadeh, Golnaz; Dashti-Rahmatabadi, Mohammad Hossein; Zanbagh, Samira; Akhavi Mirab-bashii, Atefehsadat

2015-01-01

Mumijo (shilajit) has been well known in traditional medicine as a remedy for a number of diseases, such as bone fractures, wounds, inflammation, and headache. It is also widely used as an analgesic agent in folk medicine, but no scientific documentation exists concerning that effect. The current study was conducted to evaluate the ability of mumijo to reduce sensitivity to painful stimuli when compared with morphine sulfate and sodium diclofenac. A total of 176 animals were randomly and equally divided into 2 groups with 88 mice each-one for formalin test and the other for writhing test. For each test, the animals were allocated into 10 equal groups, based on the dosage of the analgesic, plus a negative control group, with 8 mice in each group. The analgesic effect of mumijo extract in doses of 0.75, 7.5, 75, and 750 mg/kg was assessed and compared witha group receiving distilled water-the negative control group, and that for groups receiving 1, 2, or 4 mg/kg of morphine sulfate or 10, 20, or 30 mg/kg of sodium diclofenac-the positive control groups. The results showed a significant decrease in pain intensity for all mice receiving doses of mumijo extract during a 1-h formalin test when compared with the distilled water group. For all the mumijo groups except the one receiving 750 mg/kg, the analgesic effect was significantly lower than that for the morphine sulfate group receiving 4 mg/kg. No significant differences existed between all mumijo and all diclofenac groups. In a writhing test, a significant inhibition of the pain response induced by acetic acid also occurred in all 4 mumijo-administered groups as opposed to the group receiving distilled water. No significant differences existed between the writhing response in groups receiving 75 and 750 mg/kg of mumijo and any doses of diclofenac or morphine. The comparison among the different doses of mumijo in the formalin test did not show any significant differences, but in the writhing test, the maximum dose showed a more effective analgesic action. The findings indicated a significant analgesic effect for mumijo extract on chronic pain in mice, occurring in a dose-independent manner.

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.

Anthelmintic efficacy of pumpkin seed (Cucurbita pepo Linnaeus, 1753) on ostrich gastrointestinal nematodes in a semiarid region of Paraíba State, Brazil.

PubMed

Feitosa, Thais Ferreira; Vilela, Vinícius Longo Ribeiro; Athayde, Ana Célia Rodrigues; Braga, Fábio Ribeiro; Dantas, Elaine Silva; Vieira, Vanessa Diniz; de Melo, Lídio Ricardo Bezerra

2013-01-01

The aim of this study was to verify the in vivo effectiveness of pumpkin seed (Curcubita pepo Linnaeus, 1753) in naturally infected ostriches in the Cariri zone, semiarid region of Paraíba State, Brazil. Forty-eight ostriches were used, African Black breed, of 14 to 36 months old, naturally infected by gastrointestinal nematodes. These animals were divided into four groups of 12 ostriches. Group 1 consists of animals treated with 0.5 g/kg live weight (l. w.) of pumpkin seed meal; group 2 received 1 g/kg l. w. of pumpkin seed meal; group 3 was treated with Albendazole 5 %, at the dosage of 1 mL/10 kg l. w.; and Group 4 was the control group and do not received treatment. Groups 1 and 2 received the treatment for three consecutive days, orally, at intervals of 7 days, totaling nine administrations. The Albendazole 5 % was administered one time, at the beginning of the experiment, according to the manufacturer's recommendations. The groups treated with pumpkin seed showed a significant decrease in egg counts per gram of feces (EPG), wherein group 2 (1 g/kg l. w.) was the most effective. The control and drug groups showed no reduction in EPG. The results of the present study demonstrate that the administration of pumpkin seed was effective in controlling gastrointestinal helminths in naturally infected ostriches.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

NASA Astrophysics Data System (ADS)

Cadena, M. S. Reyes; Chapul, L. Sánchez; Pérez, Javiér; García, M. N. Jiménez; López, M. A. Jiménez; Espíndola, M. E. Sánchez; Perez, R. Paniagua; Hernández, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodríguez

2008-08-01

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-β) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

PubMed Central

Kuduban, Ozan; Mazlumoglu, Muhammed Recai; Kuduban, Selma Denktas; Erhan, Ertugrul; Cetin, Nihal; Kukula, Osman; Yarali, Oguzhan; Cimen, Ferda Keskin; Cankaya, Murat

2016-01-01

ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX. PMID:27812611

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.

PubMed

Gardiner, T A; Anderson, H R; Degenhardt, T; Thorpe, S R; Baynes, J W; Archer, D B; Stitt, A W

2003-09-01

To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

TEN- AND NINETY-DAY TOXICITY STUDIES OF 1,2-DICHLOROBENZENE ADMINISTERED BY ORAL GAVAGE TO SPRAGUE-DAWLEY RATS

EPA Science Inventory

Subacute (10-day) and subchronic (90-day) toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats. ,2-Dichlorobenzene was administered in corn oil by oral gavage; control animals received corn oil. t time of sacrifice, gross necropsies ...

76 FR 51934 - Determination of Pest-Free Areas in Mendoza Province, Argentina; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... acknowledged Argentina's history of successful Medfly control efforts, but stated that APHIS should not relax...] Determination of Pest-Free Areas in Mendoza Province, Argentina; Request for Comments AGENCY: Animal and Plant... received a request from the Government of Argentina to recognize additional areas as pest- free areas for...

Steroids reduce the periapical inflammatory and neural changes after pulpectomy.

PubMed

Holland, G R

1996-09-01

Root canal treatment, including obturation with gutta-percha and a zinc oxide and eugenol sealer, was conducted, under general anesthesia, on the canine teeth of 12 young ferrets. Six of the ferrets were given 0.5 mg/kg dexamethasone daily. Three months after the root canal treatment, under general anesthesia, the animals were perfused with fixative and the canine periapical tissues prepared for histological examination. The extent of periapical inflammation was measured and the degree of neural sprouting in the periodontal and subapical regions estimated. Periapical lesions in steroid-treated animals were 30% of the size of those in untreated animals. Innervation density in the subapical region of the steroid-treated animals was lower than that in the animals who did not receive steroids and not significantly different from controls. Reduction in periapical inflammation induced by systemic steroids is accompanied by a reduction in neural sprouting.

Study of the efficiency of transplantation of human neural stem cells to rats with spinal trauma: the use of functional load tests and BBB test.

PubMed

Lebedev, S V; Karasev, A V; Chekhonin, V P; Savchenko, E A; Viktorov, I V; Chelyshev, Yu A; Shaimardanova, G F

2010-09-01

Human ensheating neural stem cells of the olfactory epithelium were transplanted to adult male rats immediately after contusion trauma of the spinal cord at T9 level rostrally and caudally to the injury. Voluntary movements (by a 21-point BBB scale), rota-rod performance, and walking along a narrowing beam were monitored weekly over 60 days. In rats receiving cell transplantation, the mean BBB score significantly increased by 11% by the end of the experiment. The mean parameters of load tests also regularly surpassed the corresponding parameters in controls. The efficiency of transplantation (percent of animals with motor function recovery parameters surpassing the corresponding mean values in the control groups) was 62% by the state of voluntary motions, 37% by the rota-rod test, and 32% by the narrowing beam test. Morphometry revealed considerable shrinking of the zone of traumatic damage in the spinal cord and activation of posttraumatic remyelination in animals receiving transplantation of human neural stem cells.

Sodium benzoate, a food preservative, induces anxiety and motor impairment in rats.

PubMed

Noorafshan, Ali; Erfanizadeh, Mahboobeh; Karbalay-Doust, Saied

2014-01-01

To investigate the behavioral characteristics, including anxiety and motor impairment, in sodium benzoate (NaB) treated rats. The study was carried out between July and September 2012 in the Laboratory Animal Center of Shiraz University of Medical Sciences, Shiraz, Iran. The rats were divided into 2 groups receiving distilled water and NaB (200mg/kg/day). All the animals received daily gavages for 4 weeks. At the end of the fourth week, anxiety, and motor function were assessed in elevated plus maze and rotarod test. According to the results, NaB-treated rats spent less time in the open arm and had fewer entrances to the open arms in comparison with the control group (p<0.04). Also, the performance of the NaB-treated rats in fixed and accelerating speed rotarods was impaired, and the riding time (endurance) was lower than the control group (p<0.01). The performance of the NaB-treated rats was impaired in the elevated plus maze, an indicator of anxiety. Their riding time in fixed and accelerating speed rotarods was decreased, indicating motor impairment.

78 FR 11138 - Agency Information Collection Activities; OMB Approval Received

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2009-0070] Agency Information Collection Activities; OMB Approval Received AGENCY: Animal and Plant Health... in the Animal and Plant Health Inspection Service's final rule regarding the possession, use, and...

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

PubMed Central

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

2010-01-01

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

Evidence for Protection against Chronic Hepatitis C Virus Infection in Chimpanzees by Immunization with Replicating Recombinant Vaccinia Virus▿

PubMed Central

Youn, Jin-Won; Hu, Yu-Wen; Tricoche, Nancy; Pfahler, Wolfram; Shata, Mohamed Tarek; Dreux, Marlene; Cosset, François-Loic; Folgori, Antonella; Lee, Dong-Hun; Brotman, Betsy; Prince, Alfred M.

2008-01-01

Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved HCV infection. The difference in the rate of chronicity between the immunized and the control animals was close to statistical significance (P = 0.067). Immunized animals developed vigorous gamma interferon enzyme-linked immunospot responses and moderate proliferative responses. To investigate cross-genotype protection, the immunized recovered chimpanzees were challenged with a pool of six major HCV genotypes. During the acute phase after the multigenotype challenge, all animals had high-titer viremia in which genotype 4 dominated (87%), followed by genotype 5 (13%). However, after fluctuating low-level viremia, the viremia finally turned negative or persisted at very low levels. This study suggests the potential efficacy of replicating recombinant vaccinia virus-based immunization against chronic HCV infection. PMID:18753204

Effects of malate supplementation on acid-base balance and productive performance in growing/finishing bull calves fed a high-grain diet.

PubMed

Castillo, Cristina; Benedito, Jose Luis; Pereira, Victor; Méndez, Jesus; Vazquez, Patricia; López-Alonso, Marta; Hernández, Joaquin

2008-02-01

This study investigated the effects of malate supplementation on blood acid-base balance and serum lactate levels in a 137-day feedlot experiment with bull calves. Animals were allotted to one of two experimental groups: (1) A control group (no supplementation), and (2) a group receiving a salt of DL-malic acid. Blood pH, pCO2, HCO3-, base excess, serum L-lactate and productivity parameters were evaluated. Our data reveal that under the conditions of the present experiment malate supplementation did not have any significant effect on productivity parameters by comparison with non-supplemented animals. As regards acid-base balance, no significant effects attributable only to malate were observed. In conclusion, the time-course and the overall means of serum L-lactate for both groups in both growing and finishing periods (0.44 +/- 0.04 mmol/l and 0.39 +/- 0.02 mmol/l, respectively, for control animal; and 0.54 +/- 0.03 mmol/l and 0.49 +/- 0.01 mmol/l, respectively, for supplemented animals) suggests that malate does not have any beneficial effects in animals fed a diet of similar characteristics to that given in this study.

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.

Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

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

Sutjipto, S.; Pedersen, N.C.; Miller, C.J.

1990-05-01

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spitemore » of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.« less

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

PubMed

Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V

2007-04-01

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vaccine intranasally.

PubMed

Tesoro Cruz, Emiliano; Feria Romero, Iris Angélica; López Mendoza, Juan Gabriel; Orozco Suárez, Sandra; Hernández González, Rafael; Favela, Francisco Blanco; Pérez Torres, Armando; José Alvaro Aguilar Setién

2008-12-09

We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.

Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice

PubMed Central

Hamer, Mary; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E.; Obenaus, André

2016-01-01

Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1–7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI. PMID:26796696

Radiation exposure prior to traumatic brain injury induces responses that differ as a function of animal age

PubMed Central

2014-01-01

Purpose: Uncontrolled radiation exposure due to radiological terrorism, industrial accidents or military circumstances is a continuing threat for the civilian population. Age plays a major role in the susceptibility to radiation; younger children are at higher risk of developing cognitive deterioration when compared to adults. Our objective was to determine if an exposure to radiation affected the vulnerability of the juvenile hippocampus to a subsequent moderate traumatic injury. Materials and methods: Three-week-old (juvenile) and eight-week-old young adult C57BL/J6 male mice received whole body cesium-137 (137Cs) irradiation with 4 gray (Gy). One month later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Two months post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains frozen for immunohistochemical assessment of activated microglia and neurogenesis in the hippocampal dentate gyrus. Results: All animals were able to learn the water maze task; however, treatment effects were seen when spatial memory retention was assessed. Animals that received irradiation as juveniles followed by a moderate traumatic brain injury one month later did not show spatial memory retention, i.e., were cognitively impaired. In contrast, all groups of animals that were treated as adults showed spatial memory retention in the probe trials. Conclusion: Although the mechanisms involved are not clear, our results suggest that irradiation enhanced a young animal's vulnerability to develop cognitive injury following a subsequent traumatic injury. PMID:24164494

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

PubMed Central

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

1997-01-01

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

E. coli O124 K72 alters the intestinal barrier and the tight junctions proteins of guinea pig intestine.

PubMed

Ren, Xiaomeng; Zhu, Yanyan; Gamallat, Yaser; Ma, Shenhao; Chiwala, Gift; Meyiah, Abdo; Xin, Yi

2017-10-01

Our research group previously isolated and identified a strain of pathogenic Escherichia coli from clinical samples called E. coli O124 K72. The present study was aimed at determining the potential effects of E. coli O124 K72 on intestinal barrier functions and structural proteins integrity in guinea pig. Guinea pigs were grouped into three groups; control (CG); E. coli O124 K72 (E. coli); and probiotics Lactobacillus rhamnosus (LGG). Initially, we create intestinal dysbiosis by giving all animals Levofloxacin for 10days, but the control group (CG) received the same volume of saline. Then, the animals received either E. coli O124 K72 (E. coli) or Lactobacillus rhamnosus (LGG) according to their assigned group. E. coli O124 K72 treatment significantly affected colon morphology and distorted intestinal barrier function by up-regulating Claudin2 and down-regulating Occludin. In addition, E. coli upregulated the mRNA expression of MUC1, MUC2, MUC13 and MUC15. Furthermore, suspected tumor was found in the E. coli treated animals. Our results suggested that E. coli O124 K72 strain has adverse effects on intestinal barrier functions and is capable of altering integrity of structural proteins in guinea pig model while at same time it may have a role in colon carcinogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Global gene expression in the bovine corpus luteum is altered after stimulatory and superovulatory treatments.

PubMed

Fátima, Luciana A; Baruselli, Pietro S; Gimenes, Lindsay U; Binelli, Mario; Rennó, Francisco P; Murphy, Bruce D; Papa, Paula C

2013-01-01

Equine chorionic gonadotrophin (eCG) has been widely used in superovulation and artificial insemination programmes and usually promotes an increase in corpus luteum (CL) volume and stimulates progesterone production. Therefore, to identify eCG-regulated genes in the bovine CL, the transcriptome was evaluated by microarray analysis and the expression of selected genes was validated by qPCR and western blot. Eighteen Nelore crossbred cows were divided into control (n=5), stimulated (n=6) and superovulated groups (n=7). Ovulation was synchronised using a progesterone device-based protocol. Stimulated animals received 400 IU of eCG at device removal and superovulated animals received 2000 IU of eCG 4 days prior. Corpora lutea were collected 7 days after gonadotrophin-releasing hormone administration. Overall, 242 transcripts were upregulated and 111 transcripts were downregulated in stimulated cows (P ≤ 0.05) and 111 were upregulated and 113 downregulated in superovulated cows compared to the control animals (1.5-fold, P ≤ 0.05). Among the differentially expressed genes, many were involved in lipid biosynthesis and progesterone production, such as PPARG, STAR, prolactin receptors and follistatin. In conclusion, eCG modulates gene expression differently depending on the treatment, i.e. stimulatory or superovulatory. Our data contribute to the understanding of the pathways involved in increased progesterone levels observed after eCG treatment.

Dried, ground banana plant leaves (Musa spp.) for the control of Haemonchus contortus and Trichostrongylus colubriformis infections in sheep.

PubMed

Gregory, L; Yoshihara, E; Ribeiro, B L M; Silva, L K F; Marques, E C; Meira, E B S; Rossi, R S; Sampaio, P H; Louvandini, H; Hasegawa, M Y

2015-12-01

To evaluate the anthelmintic effect of Musa spp. leaves, 12 animals were artificially infected with Haemonchus contortus, and another 12 animals were infected with Trichostrongylus colubriformis. Then, both treatment groups were offered 400 g of dried ground banana plant leaves, and the control animals were offered only 1000 g of coast cross hay. During the trials, the animals received weekly physical examinations. The methods used to evaluate the efficiency of this treatment were packed cell volume, total plasma protein and faecal egg counts, and egg hatchability tests were performed on days -2, +3, +6, +9, +13 and +15. Coproculture tests were performed on day -2 to confirm monospecific infections. In the FEC and EHT, a statistically significant difference (0.04, 0.005; p < 0.05) was noted for T. colubriformis. There were no statistically significant differences (p > 0.05) for Haemochus contortus group in all tests. Our results confirmed previous findings suggesting that dried ground banana plant leaves possess anthelmintic activity.

Effect of preservation methods of oil palm sap (Elaeis guineensis) on the reproductive indices of male wistar rats.

PubMed

Ikegwu, Theophilus Maduabuchukwu; Okafor, Gabriel Ifeanyi; Ochiogu, Izuchukwu Shedrack

2014-12-01

Thirty male Wistar rats, split into five groups of six rats each, were administered different forms of oil palm tree (Elaeis guineensis) sap samples by gavage based on 1.5% of their weekly body weights. Group 1 which served as control received only water, group 2 received pasteurized palm sap (PPS), group 3 received market palm wine (MPW), group 4 received frozen palm sap (FPS), whereas group 5 received fresh palm sap (FrPS). Chemical composition of the sap samples was determined. Normal feed and water were fed ad libitum. After 2 months of treatment, each male rat group was allowed 7 days to mate with six female Wistar rats. Thereafter, blood and epididymal samples were collected for testosterone assay and sperm count, respectively, before they were humanely sacrificed and testicular tissues taken for testicular histology. Litter weight and size of the pups produced by the females of each group were determined at birth. The sap samples contained carbohydrate (0.01-11.71%), protein (1.56-1.95%), ash (0.22-0.35%), moisture (92.55-98.24%), and alcohol (0.26-3.50%). PPS-treated rat group had significantly (P<.05) decreased sperm count (42.60±23.64×10(6)), abnormal increase in testosterone level, and necrosis in the histology of the testes with reduced spermatogenetic activity, compared with other treatment groups. The female rats crossed with male rats fed on FrPS or FPS produced the highest number of pups followed by the control group. This study demonstrated that the intake of FrPS improved fertility in male animals, but its administration for a long period led to necrotic changes in the testes, whereas pasteurization of palm sap, impacted negatively on the reproductive indices of male animals.

The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats.

PubMed

Gokbulut, C; Karademir, U; Boyacioglu, M; McKellar, Q A

2008-10-01

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.

Effectiveness of selenium on acrylamide toxicity to retina

PubMed Central

Ali, Mervat Ahmed; Aly, Eman Mohamed; Elawady, Amal Ibrahim

2014-01-01

AIM To investigate the hematological parameters, biochemical and electrophysiological role of acrylamide (ACR) in the retina and to assess whether selenium (Se) has protective potential in experimental oral intoxication with ACR. METHODS Sixty Wistar age matched-albino rats (3mo) weighing 195-230 g comprised of both sex were divided into 4 groups. Group I served as the control one in which animals take saline; group II was animals administrated ACR in dose of 15 mg/kg body weight per day for 28d; group III was animals received ACR then additionally Se (0.1 mg/kg body weight) for 28d; and group IV was animals received Se only (0.1 mg/kg body weight) for 28d. Blood analysis and serum trace element levels (Fe, Cu, and Zn) were measured. The electroretinogram (ERG) was recorded, the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in the retinal tissues were determined. Moreover the regulation of ion channels such as calcium, sodium and potassium were studied. All measurements were done for all groups after 28d. RESULTS Administration of ACR in group II caused a significant decrease (P<0.05) in hemoglobin (Hb), red blood cells (RBCs), hematocrit (HCT), white blood cells (WBCs) and lymphocyte of rats. A significant decrease (P<0.05) in Zn level, and alkaline phosphatase enzyme was observed compared to control. ERG which is a reflection of the electric activity in the retina; a- and-b wave amplitudes in ACR group had a reduction of 40% and 20% respectively. These changes accompanied by significant increases (P<0.05) in MDA level in the ACR group, in contrast with GSH-Px which is significant decreased (P<0.05). Moreover sodium and calcium were significant increased but potassium was significant decreased (P<0.05) compared to control group. There were no significant differences between group III (treated with Se) and control in all hematological parameter. Also serum trace elements levels (Cu, Fe and Zn), alkaline phosphatase enzyme and electric activity of the retina didn't change compared to control due to Se treatment. CONCLUSION This study provides evidence for the protective effect of Se on acrylamide induced toxicity by reducing oxidative stress. PMID:25161930

Early Adverse Experience Increases Emotional Reactivity in Juvenile Rhesus Macaques: Relation to Amygdala Volume

PubMed Central

Howell, B.R.; Grand, A. P.; McCormack, K. M.; Shi, Y.; LaPrarie, J.; Maestripieri, D.; Styner, M. A.; Sanchez, M. M.

2015-01-01

This study investigated the impact of infant maltreatment on juvenile rhesus monkeys’ behavioral reactivity to novel stimuli and its associations with amygdala volume. Behavioral reactivity to novel stimuli of varying threat intensity was measured using Approach/Avoidance (AA) and Human Intruder (HI) tasks. In vivo magnetic resonance imaging (MRI) was used to measure amygdala volume. Interestingly, group behavioral differences were context-dependent. When exposed to a human intruder, maltreated subjects displayed more anxious behaviors than controls; however, when presented with fear-evoking objects, maltreated animals exhibited increased aggression and a shorter latency to inspect the objects. Finally, under testing conditions with the lowest levels of threat (neutral novel objects) maltreated animals also showed shorter latencies to inspect objects, and reduced avoidance and increased exploration compared to controls. This suggests alterations in threat assessment and less behavioral inhibition in animals with early adverse experience compared to controls. Some of these behavioral responses were associated with amygdala volume, which was positively correlated with abuse rates received during infancy, particularly reflecting a relationship with exploration, consistent with previous studies. PMID:25196846

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

PubMed Central

Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

1991-01-01

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7.9 +/- 1.9 microns versus 34.0 +/- 13.0 microns, analysis of variance: p = 0.054). Low-dose safflower oil also had a slight, but nonsignificant, beneficial effect on graft vessel disease when compared to control rabbits. The same trends were observed in the degree of histologic rejection (0 = none to 3 = severe) in fish oil- and safflower oil-treated animals. Rejection score correlated weakly but significantly (p = 0.0001) with mean luminal occlusion (r = 0.52) and intimal thickness (r = 0.46). Therefore allograft coronary disease in this model appeared to exhibit an unfavorable, direct-dose response to fish oil and safflower oil, independent of effects on plasma lipids.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 2. PMID:1867523

Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain.

PubMed

Abdulmajeed, Wahab Imam; Ibrahim, Ridwan Babatunde; Ishola, Azeez Olakunle; Balogun, Wasiu Gbolahan; Cobham, Ansa Emmanuel; Amin, Abdulbasit

2016-03-01

Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both 'Y' maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the 'Y' maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

Investigation of blood lead concentrations in dogs living in Flint, Michigan.

PubMed

Langlois, Daniel K; Kaneene, John B; Yuzbasiyan-Gurkan, Vilma; Daniels, Barbara L; Mejia-Abreu, Hilda; Frank, Nancy A; Buchweitz, John P

2017-10-15

OBJECTIVE To measure blood lead concentrations (BLCs) in dogs living in Flint, Mich, following a declared water crisis and to assess potential associations of BLCs with demographic data, water sources, and clinical signs in these dogs. DESIGN Cross-sectional study. ANIMALS 284 dogs residing in Flint, Mich (test population), and 47 dogs residing in East Lansing, Mich (control population), and immediately adjacent areas. PROCEDURES Blood samples were collected at free screening clinics in Flint (test population) and at the Michigan State University College of Veterinary Medicine Veterinary Medical Center (control population). Owners of test population dogs completed questionnaires providing demographic and clinical information. Hematologic evaluations were performed; BLCs were measured by inductively coupled plasma-mass spectrometry. RESULTS 4 of 284 test population dogs had BLCs > 50 ppb; an additional 20 had BLCs > 20 ppb. Overall, BLCs of test population dogs were higher than those of control dogs. Within the test population, young dogs (≤ 2 years of age) had higher BLCs than old dogs (≥ 6 years of age). Only 7.2% of test population dogs were drinking unfiltered tap water at the time of screening; however, dogs that had been receiving filtered or bottled water for ≤ 3 months before screening had higher BLCs than did those that received such water for > 3 months. CONCLUSIONS AND CLINICAL RELEVANCE Taken together, findings suggested that the impact of the Flint water crisis extended to companion animals. Results highlighted the importance of maintaining awareness of lead exposure and considering both human and animal well-being in cases of environmental toxicant exposures.

Transient disruption of vascular barriers using focused ultrasound and microbubbles for targeted drug delivery in the brain

NASA Astrophysics Data System (ADS)

Aryal, Muna

The physiology of the vasculature in the central nervous system (CNS) which includes the blood-brain-barrier (BBB) and other factors, prevents the transport of most anticancer agents to the brain and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels (blood-tumor barrier; BTB), along with several other factors, creates additional hurdles for drug treatment of brain tumors. Different methods have been used to bypass the BBB/BTB, but they have their own limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Magnetic Resonance Imaging guided Focused Ultrasound (MRIgFUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and BTB. The purpose of this thesis was to use this alternative approach to deliver chemotherapeutic agents through the BBB/BTB for brain tumor treatment in a rodent model to overcome the hinderances encountered in prior approaches tested for drug delivery in the CNS. The results presented in thesis demonstrate that MRIgFUS can be used to achieve consistent and reproducible BBB/BTB disruption in rats. It enabled us to achieve clinically-relevant concentrations of doxorubicin (~ 4.8+/-0.5 microg/g) delivered to the brain with the sonication parameters (0.69 MHz; 0.55 MPa; 10 ms bursts; 1 Hz PRF; 60 s duration), microbubble concentration (Definity, 10 microl/kg), and liposomoal doxorubicin (Lipo-DOX) dose (5.67 mg/kg) used. The resulting doxorubicin concentration was reduced by 32% when the agent was injected 10 minute after the last sonication. Three weekly sessions of FUS and Lipo-DOX appeared to be safe in the rat brain, despite some minor tissue damage. Importantly, the severe neurotoxicity seen in earlier works using other approaches does not appear to occur with delivery via FUS-BBB disruption. The resuls from three weekly treatments of FUS and Lipo-DOX in a rat glioma model are highly promising since they demonstrated that the method significantly inhibits tumor growth and improves survival. Animals that received three weekly sessions of FUS + Lipo-DOX (N = 8) had a median survival time that was increased significantly (P<0.001) compared to animals who received Lipo-DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7). Median survival for animals that received FUS + Lipo-DOX was increased by 100% relative to untreated controls, whereas animals who received Lipo-DOX alone had only a 16% improvement. Animals who received only FUS showed no improvement. No tumor cells were found in histology in 4/8 animals in the FUS + Lipo-DOX group, and only a few tumor cells were detected in two animals. Tumor doxorubicin concentrations increased monotonically (823+/-600, 1817+/-732 and 2432+/-448 ng/g) in the control tumors at 9, 14 and 17 days respectively after administration of Lipo-DOX. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P<0.05, P<0.01, and P<0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222+/-784, 3687+/-796 and 5658+/-821 ng/g) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (p<0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery for Lipo-DOX are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da). Overall, this thesis research provides pre-clinical data toward the development of MRIgFUS as a noninvasive method for the delivery of agents such as Lipo-DOX across the BBB/BTB to treat patients with diseases of the central nervous system.

[The use of pectin-containing enterosorbents in exposure to radionuclides and heavy metals].

PubMed

Trakhtenberg, I M; Litenko, V A; Dereviago, I B; Demchenko, P I; Mikhaĭlovskiĭ, S V

1992-05-01

The pectin-vitamin composition (PVC) and its complex with active carbon (AC) was investigated for use as an oral sorbent to protect radionuclide (Sr-85, Cs-137) accumulation. PVC is composed of the natural mixture of cellulose, pectin (Ca-salt), flavonoides, vitamins of the B-group, PP and C. Investigation of PVC radioprotective action was carried out on the two groups of rats (n = 30) which received 1306 Bk/animal of Sr-85 or 343 Bk/animal of Cs-137 daily. One of the group of rats received every day also 300 mg of PVC. After 30 days level of Sr-85 was less by 56.6%, level of Cs = 137 was less by 27.6% in PVC-treated than in the control group (P < 0.05). Composite sorbent consisting of PVC and AC was slightly less effective in removing of Sr and Cs.

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

PubMed

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

2013-06-04

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

Adaptation of Diaphyseal Structure with Aging and Increased Mechanical Usage in the Adult Rat: A Histomorphometrical and Biomechanical Study

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.; Li, Xiao Jian; Schaffler, Mitchell B.

1991-01-01

The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling. The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment.

Adaptation of Diaphyseal Structure With Aging and Increased Mechanical Usage in the Adult Rat: A Histomorphometrical and Biomechanical Study

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.; Li, Xiao Jian; Schaffler, Mitchell B.

1991-01-01

The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling. The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment.

THE RELATIONSHIP BETWEEN REAL-TIME AND TIME-INTEGRATED COARSE (2.5-10MM), INTERMEDIATE (1-2.5MM), AND FINE (<2.5MM) PARTICULATE MATTER IN THE LOS ANGELES BASIN

EPA Science Inventory

Population exposure to ambient particulate matter (PM) has received considerable attention due to the association between ambient particulate concentrations and mortality. Current toxicological and epidemiological studies and controlled human and animal exposures suggest that a...

Protein Synthesis Inhibition Blocks Consolidation of an Acrobatic Motor Skill

ERIC Educational Resources Information Center

Kaelin-Lang, Alain; Dichgans, Johannes; Schulz, Jorg B.; Luft, Andreas R.; Buitrago, Manuel M.

2004-01-01

To investigate whether motor skill learning depends on de novo protein synthesis, adult rats were trained in an acrobatic locomotor task (accelerating rotarod) for 7 d. Animals were systemically injected with cycloheximide (CHX, 0.5 mg/kg, i.p.) 1 h before sessions 1 and 2 or sessions 2 and 3. Control rats received vehicle injections before…

Impairment of Bony Crypt Development Associated With Hexavalent Chromium Exposure During Tooth Eruption.

PubMed

Sánchez, Luciana M; Lewicki, Marianela; De Lucca, Romina C; Ubios, Ángela M

2015-12-01

Improperly treated hexavalent chromium-containing industrial wastes contaminate drinking water, potentially affecting children taking breast milk or baby bottles prepared with infant formula. Thus, the aim of the present work was to determine the effect of this toxic on bone activity in the developing alveolus during tooth eruption of suckling Wistar rats intoxicated with potassium dichromate. Experimental animals received a daily dose of 12.5mg/kg body weight of potassium dichromate by gavage for 10 days; controls received an equivalent volume of saline solution. Histologic and histomorphometric studies of the mandible were performed. The data were statistically analyzed using Student's t test; statistical significance was set at a value of p <0.05. Experimental animals exhibited delayed tooth eruption, decreased periodontal width and bone volume, a lower percentage of bone formation surfaces, and higher percentage of quiescent surfaces (p<0.05) compared to controls. The delay in tooth eruption observed after exposure to hexavalent chromium is the result of a lower rate of bone remodeling in the developing alveolus. The obtained results show the importance of controlling toxic substances in drinking water, since their effects may alter the growth and development of subjects who were exposed during early infancy. Sociedad Argentina de Investigación Odontológica.

A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution.

PubMed

Seitenfus, Rafael; Ferreira, Paulo Roberto Walter; Santos, Gabriel Oliveira Dos; Alves, Rafael José Vargas; Kalil, Antonio Nocchi; Barros, Eduardo Dipp de; Glehen, Olivier; Casagrande, Thaís Andrade Costa; Bonin, Eduardo Aimoré; Silva Junior, Edison Martins da

2017-12-01

To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

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.

Use of implantable telemetry systems for study of cardiovascular phenomena.

NASA Technical Reports Server (NTRS)

Sandler, H.; Fryer, T. B.; Westbrook, R. M.; Stone, H. L.

1972-01-01

Preliminary observations of cardiovascular function have been made in four chimpanzees using multichannel implantable units. Measurements of right- and left-sided pressures were periodically made in these animals over a four-month period, including continuous observations for selected 24-hour periods. Pressures recorded with animals in an awake, unanesthetized, unrestrained state were much lower than pressures reported for restrained animals in similar situations. Diurnal variations of pressure tended to occur, but were not as clear-cut as those reported to occur for humans. The ability to implant a transmitter chronically and receive useful multichannel information in the chimpanzee encourages the future use of such implant devices as part of the control system for an artificial heart or directly for use in man.

Humoral Immune Response After Intravitreal But Not After Subretinal AAV8 in Primates and Patients.

PubMed

Reichel, Felix F; Peters, Tobias; Wilhelm, Barbara; Biel, Martin; Ueffing, Marius; Wissinger, Bernd; Bartz-Schmidt, Karl U; Klein, Reinhild; Michalakis, Stylianos; Fischer, M Dominik

2018-04-01

To study longitudinal changes of anti-drug antibody (ADA) titers to recombinant adeno-associated virus serotype 8 (rAAV8) capsid epitopes in nonhuman primates (NHP) and patients. Three groups of six NHP each received subretinal injections (high dose: 1 × 1012 vector genomes [vg], low dose: 1 × 1011 vg, or vehicle only). Four additional animals received intravitreal injections of the high dose (1 × 1012 vg). Three patients received 1 × 1010 vg as subretinal injections. ELISA quantified ADA levels at baseline and 1, 2, 3, 7, 28, and 90 days after surgery in NHP and at baseline and 1, 3, and 6 months after surgery in patients. Two out of 22 animals lacked ADA titers at baseline and developed low ADA titers toward the end of the study. Titers in the low-dose group stayed constant, while two of six animals from the high-dose group developed titers that rose beyond the range of the assay. All animals from the intravitreal control group showed a rise in ADA titer by day 7 that peaked at day 28. Preliminary data from the clinical trial (NCT02610582) show no humoral immune response in patients following subretinal delivery of 1 × 1010 vg. No significant induction of ADA occurred in NHP when mimicking the clinical scenario of subretinal delivery with a clinical-grade rAAV8 and concomitant immunosuppression. Likewise, clinical data showed no humoral immune response in patients. In contrast, intravitreal delivery was associated with a substantial humoral immune response. Subretinal delivery might be superior to an intravitreal application regarding immunologic aspects.

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.

Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

NASA Technical Reports Server (NTRS)

Winget, C. M.; Syrkin, N.; Heeke, D.; Mele, G.; Holley, D. C.; Dalton, Bonnie P. (Technical Monitor)

1996-01-01

Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and for microgravity animal habitats.

Effects of Dietary Supplementation with Agaricus sylvaticus Schaeffer on Glycemia and Cholesterol after Streptozotocin-Induced Diabetes in Rats

PubMed Central

Mascaro, Marcelo Betti; França, Cristiane Miranda; Esquerdo, Kamilla F.; Lara, Marx A. N.; Wadt, Nilsa S. Y.; Bach, Erna E.

2014-01-01

This study evaluated the effect of the Agaricus sylvaticus (sun mushroom) on biochemical tests of the plasma and on the morphology of the pancreas in an experimental model of type I diabetes mellitus (DM1) induced by streptozotocin. One gram of dry A. sylvaticus was homogenized and mixed with the chow. Male Wistar rats were allocated as follows: normoglycemic control that received commercial chow; normoglycemic control group that received chow with A. sylvaticus; diabetic group that received commercial chow; and diabetic group that received chow with A. sylvaticus. Weight, food, and water consumption were measured every two days. Blood glucose levels were measured twice a week. After 30 days, the animals were euthanized and blood was collected for the analysis of cholesterol, HDL, triglycerides, blood sugar, glutamic-pyruvic transaminase (GPT), alkaline phosphatase, iron, transferrin, and urea. The pancreas was processed for microscopic analysis. A. sylvaticus modulated the levels of cholesterol, HDL, triglycerides, blood sugar, GPT, alkaline phosphatase, iron, transferrin, and urea to levels similar to those found in the controls and led to compensatory hyperplasia of the islets of Langerhans. A. sylvaticus is potentially beneficial in the control of type 1 diabetes, and it may also prevent pancreas damage. PMID:24971142

Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium.

PubMed

Czompa, Attila; Gyongyosi, Alexandra; Szoke, Kitti; Bak, Istvan; Csepanyi, Evelin; Haines, David D; Tosaki, Arpad; Lekli, Istvan

2017-03-20

Objective : A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods : Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results : Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio-an outcome associated with decreased risk of atherosclerotic disease. Conclusions : BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases.

Preventing pressure sores of the nasal ala after nasotracheal tube intubation: from animal model to clinical application.

PubMed

Huang, Tze-Ta; Tseng, Chih-En; Lee, Tsan-Mu; Yeh, Jen-Ying; Lai, Yu-Yung

2009-03-01

Nasal-ala pressure sores induced by nasotracheal intubation are common complications of oral and maxillofacial surgery, but are easily ignored. To determine whether such sores could be prevented, we studied the effects of a combination of cushioning material in an animal model, and then analyzed the efficacy of this combination clinically. Four pigs received nasotracheal intubation. Each pig received intubation for 4, 8, 12, or 16 hours. Outcomes from pigs undergoing 500-gram-weight compression on each nostril were compared: one nostril received an application of cushioning materials, and the contralateral nostril did not. After the required study period, clinical assessment and further evaluation were performed by measuring pressure-sore dimensions and performing incisional biopsies. Clinical applications of this protective technique were then undertaken. Eight patients who underwent intubation without Soft Liner (GC Co, Tokyo, Japan) and DuoDERM CGF (ConvaTec, Inc, Princeton, NJ) protection, and 10 patients with Soft Liner and DuoDERM protection, were evaluated. The protective efficacy of the cushioning materials was significant in the animal model as well as in clinical practice. Pressure sores were avoided on the protected side, with severe tissue necrosis documented on the control side. We found that the combined use of Soft Liner and DuoDERM reduced the size and severity of nasal-ala pressure sores attributable to nasotracheal intubation during oral and maxillofacial surgery.

FAMACHA(©) method as an auxiliary strategy in the control of gastrointestinal helminthiasis of dairy goats under semiarid conditions of Northeastern Brazil.

PubMed

Vilela, Vinícius Longo Ribeiro; Feitosa, Thais Ferreira; Linhares, Emanuel Figueiredo; Athayde, Ana Célia Rodrigues; Molento, Marcelo Beltrão; Azevedo, Sérgio Santos

2012-11-23

This study aimed to evaluate the utilization of FAMACHA(©) method as an auxiliary strategy to use the individual identification for the selective control of gastrointestinal helminthiasis in naturally infected dairy goats. The experiment was conducted on 63 farms in the towns of Passagem, Quixabá and Cacimba de Areia, semiarid region of the Paraíba state, Brazil. Fifty animals were used on each farm, being visited tree farms per month, totaling 1800 animals, between May 2009 and April 2010. The animals received no anthelmintic treatment for at least four months prior to the farm visits. All animals were subjected to parasitological faecal collection, blood sampling for packed cell volume and the visual/selective exam of the eye colour through the FAMACHA(©) method. Larvae culture was performed in every assessment on each farm. Haemonchus sp. was the most prevalent helminth (80.1%) on larval cultures. The use of this method allowed a reduction of 79.2% on anthelmintic application in dairy goats. The FAMACHA(©) method proved to be a viable auxiliary strategy to control gastrointestinal helminthiasis of dairy goats from a resource-poor area in the semiarid region of the Paraíba state, Northeastern Brazil. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Round window administration of gentamicin: a new method for the study of ototoxicity of cochlear hair cells.

PubMed

Husmann, K R; Morgan, A S; Girod, D A; Durham, D

1998-11-01

Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.

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.

Hippocampal GABAA Receptor and Pain Sensitivity during Estrous Cycle in the Rat

PubMed Central

Taherianfard, Mahnaz; Mosavi, Mahnaz

2011-01-01

Background: Estradiol and progesterone as well as hippocampal GABAA receptors are believed to play a role in the modulation of pain. The aim of present study was to investigate the effect of intrahippocampal injections of GABAA receptor agonist (muscimol) and GABAA receptor antagonist (picrotoxin) on pain sensitivity during estrous cycle. Methods: Pain sensitivity was evaluated in rats by formalin test during all stages of estrous cycle. Animals were divided into five groups including; 1- control (intact animal); 2- sham 1 receiving 0.75 µl artificial cerebrospinal fluids (ACSF); 3- sham 2 receiving 0.75 µl alcoholic ACSF; 4- experimental 1 receiving 250 or 500 µg/rat of muscimol in 0.75 µl vehicle, and 5- experimental 2 receiving 20 or 30 µg/rat picrotoxin in 0.75 µl vehicle. Data were analyzed by Kruskal-Wallis followed by Tucky's test for pairwise comparisons using a P value of ≤0.50 for statistical significance. Results: Muscimol significantly (P<0.05) decreased pain sensitivity in all stages of estrous cycle, and the analgesic effect was higher during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Picrotoxin significantly (P<0.05) increased pain sensitivity in all stages of estrous cycle, and such a hyperalgesic effect was lower during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Conclusion: The findings of the present study indicate that the role of hippocampal GABAA receptor in the control of the pain sensitivity can be modulated by variation in gonadal steroids during different stages of the estrous cycle. PMID:23115414

Short communication: Supplementing grape marc to cows fed a pasture-based diet as a method to alter nitrogen partitioning and excretion.

PubMed

Greenwood, S L; Edwards, G R; Harrison, R

2012-02-01

The inclusion of the grape marc into livestock rations provides an opportunity not only to use a waste byproduct resourcefully, but also to induce beneficial metabolic changes in animals. Grape marc contains condensed tannins that could alter N metabolism, which would be beneficial from an environmental perspective. The objective was to determine if dietary grape marc could decrease urinary N excretion from nonlactating dairy cattle. Eighteen multiparous cows were randomly divided into 2 equal groups, receiving either (1) pasture+2 kg of dry matter (DM)/d energy pellet per cow (control group) or (2) pasture+2 kg of DM/d energy pellet per cow+3 kg of DM/d grape marc per cow. Urine, fecal, and blood samples were collected at baseline (d 0) and at d 9. Cows receiving grape marc excreted 22% more N in feces compared with the control group. Cows offered grape marc had lower plasma urea nitrogen concentrations (2.42 and 2.97±0.1 mmol/L from treatment and control cows, respectively), but had no significant difference in urine urea concentration compared with control animals (84.24 and 114.1±17.62 mmol/L from treatment and control cows, respectively). Overall, the potential exists to alter N metabolism in dairy cows using dietary grape marc. The exact mechanisms causing this shift in N metabolism require further investigation. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Visitor reaction to pacing behavior: influence on the perception of animal care and interest in supporting zoological institutions.

PubMed

Miller, Lance J

2012-01-01

Many publications within the field of zoo animal welfare have stated the importance of decreasing stereotypic behavior (e.g., pacing) to help ensure a positive visitor experience. The idea behind these statements is that visitors want to see animals engaged in natural behavior. Additionally, it is thought that watching an animal exhibit species-appropriate behavior could help increase a visitor's connection to wildlife and ultimately their interest in conservation. However, until recently, no information was available to validate such statements. The purpose of this research was to examine people's reaction to viewing an animal engaged in pacing behavior. Participants were randomly selected to fill out a survey after watching a short video of either a tiger pacing or resting (control). Results indicate that having viewed a tiger pacing significantly decreases people's perception of the level of care animals receive at that facility. In addition, people's interest in supporting zoos decreased as a result of viewing this behavior. Results are discussed from an animal welfare, business, and conservation perspective. © 2011 Wiley Periodicals, Inc.

9 CFR 351.22 - Certified plants to maintain records and make reports; access to records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR... records. (a) Each day a certified plant prepares, receives, or ships certified technical animal fat or... kinds and quantities of such materials and technical animal fats received, the number of pounds of...

9 CFR 351.22 - Certified plants to maintain records and make reports; access to records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR... records. (a) Each day a certified plant prepares, receives, or ships certified technical animal fat or... kinds and quantities of such materials and technical animal fats received, the number of pounds of...

9 CFR 351.22 - Certified plants to maintain records and make reports; access to records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR... records. (a) Each day a certified plant prepares, receives, or ships certified technical animal fat or... kinds and quantities of such materials and technical animal fats received, the number of pounds of...

The organisation of the Department of Veterinary Services in Malaysia.

PubMed

Mohd Nor, M N; Abu Mustapa, A J; Abu Hassan, M A; Chang, K W

2003-08-01

The Department of Veterinary Services (DVS) in Malaysia was established in 1888 as an agency to control exotic and domestic animal diseases. Over the years, the structure and functions of the organisation have evolved to meet the growing demand for veterinary services. The responsibilities of the Veterinary Services are enshrined in the Constitution of Malaysia. The current organisation of the DVS is structured to achieve the following objectives:---to prevent, control and eradicate animal and zoonotic diseases--to facilitate the growth and development of a strong animal industry--to ensure that animal products for human consumption are wholesome, clean, safe and suitable to be consumed--to facilitate the growth and development of the animal feed industry--to ensure the welfare and well-being of all animals. To meet these objectives the DVS has nine different divisions, as follows: Planning and Evaluation, Epidemiology and Veterinary Medicine, Veterinary Public Health, Research and Development, Industry Development, Production and Development of Genetic Resources, Human Resource Development (HRD), Enforcement, and Administration. The development of the animal industry is managed through national development policies, including the Third National Agriculture Policy. The basis for current programmes for disease control and animal industry development is the Eighth Development Plan (2001-2005). Over the period of this Plan, Malaysia will address the need for sanitary and phytosanitary measures by developing specific programmes covering all fields of the animal industry. This is just one way in which Malaysia is meeting the challenges of the increased liberalisation of trade created by the World Trade Organization and the Association of Southeast Asian Nations Free Trade Area. The development of the industry is focused on the major commodities, namely, beef, mutton, poultry meat, eggs, pork and milk. Other commodities receive support if it is considered economically viable. All support services are being strengthened, particularly the HRD division. The organisation and functions of the DVS are constantly being reviewed in accordance with changes in the animal industry and the nature of the services in demand.

The effects of intradermal and topical mitomycin C on wound healing.

PubMed

Porter, Glen T; Gadre, Swarupa A; Calhoun, Karen H

2006-07-01

To determine the effect of intradermal and topical mitomycin C (MMC) on skin wound healing. A prospective, controlled study in a rat wound model performed in an academic medical center. Intradermal and topical MMC application decreased wound integrity when compared with saline-treated animals at 1 week, 2 weeks, 1 month, and 6 months. Skin necrosis occurred in animals that received intradermal MMC. Hemotoxylin and eosin and immunohistochemical staining showed no consistent difference between treatment arms. Fibrosis and collagen deposition were reduced in MMC-treated wounds on trichrome staining. MMC-treated wounds showed decreased wound strength compared with controls. Intradermal MMC can cause skin necrosis. Histologic findings did not always correspond with clinical data. The data suggest cautious use of MMC in clinical situations when wound breaking strength is critical.

Effects of ethanol on superovulation in the immature rat following pregnant mare's serum gonadotropin (PMSG) or PMSG and human chorionic gonadotropin treatment.

PubMed

Bo, W J; Krueger, W A; Rudeen, P K

1983-05-01

We sought to determine whether superovulation could occur in immature rats on a 5% ethanol diet and treated with pregnant mare's serum gonadotropin (PMSG) alone or with human chorionic gonadotropin (hCG). Holtzman female rats were divided into five groups at 20 days of age. Six rats (Group I) were killed at that age. Ten rats (Group II) were placed on an ad libitum laboratory chow diet and killed on Day 33. Twenty-four rats (Group III) were placed on an ad libitum laboratory chow diet. Twenty-four rats (Group IV) were placed on 5% ethanol liquid diet, while 24 rats in Group V were pair-fed with the animals in Group IV. At 30 days of age, 12 rats from each Group, III, IV, and V, received 25 IU of PMSG s.c. and were killed 74-76 h later. The remaining 12 rats from each Group, III, IV and V, received 25 IU of PMSG and 54-56 h later received 10 IU of hCG and were killed 20 h later. Ovulation occurred in all the rats of Groups III and V that received PMSG alone or with hCG. In the ethanol-treated rats that received PMSG alone, 75% ovulated, while 92% ovulated that received PMSG and hCG. The number of ova shed in the ethanol-PMSG-treated rats was significantly less than in the ethanol-PMSG-hCG-treated animals and in the controls. The uterine weights and morphology of the animals in Group IV were similar to those in Groups III and V. The study indicates that ethanol does not have a direct gonadotoxic effect on the ovary but indicates that ethanol has an effect on the hypothalamus and/or the pituitary, thereby disrupting the synthesis and/or release of luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH).

Antibody responses induced by Leish-Tec®, an A2-based vaccine for visceral leishmaniasis, in a heterogeneous canine population.

PubMed

Testasicca, Miriam C de Souza; dos Santos, Mariana Silva; Machado, Leopoldo Marques; Serufo, Angela Vieira; Doro, Daniel; Avelar, Daniel; Tibúrcio, Ana Maria Leonardi; Abrantes, Christiane de Freitas; Machado-Coelho, George Luiz Lins; Grimaldi, Gabriel; Gazzinelli, Ricardo Tostes; Fernandes, Ana Paula

2014-08-29

Zoonotic visceral leishmaniasis (VL) is a widespread disease, and dogs are the main reservoirs for human parasite transmission. Hence, development of an effective vaccine that prevents disease and reduces the transmission of VL is required. As euthanasia of seropositive dogs is recommended in Brazil for VL epidemiological control, to include anti-VL canine vaccines as a mass control measure it is necessary to characterize the humoral responses induced by vaccination and if they interfere with the reactivity of vaccinated dogs in serological diagnostic tests. Leish-Tec(®) is an amastigote-specific A2 recombinant protein vaccine against canine visceral leishmaniasis (CVL) that is commercially available in Brazil. Here, we tested the immunogenicity of Leish-Tec(®) in a heterogeneous dog population by measuring A2-specific antibody responses. Healthy dogs (n=140) of various breeds were allocated to two groups: one group received Leish-Tec(®) (n=70), and the other group received a placebo (n=70). Anti-A2 or anti-Leishmania promastigote antigen (LPA) antibody levels were measured by ELISA in serum samples collected before and after vaccination. An immunochromatographic test (DPP) based on the recombinant K28 antigen was also used for serodiagnosis of CVL. Vaccinated animals, except one, remained seronegative for anti-LPA total IgG and anti-K28 antibodies. Conversely, seropositivity for anti-A2 total IgG antibodies was found in 98% of animals after vaccination. This value decreased to 81.13% at 6 months before rising again (98%), after the vaccination boost. Anti-A2 IgG2 and IgG1 titers were also increased in vaccinated animals relative to control animals. These data indicate that Leish-Tec(®) is immunogenic for dogs of different genetic backgrounds and that humoral responses induced by vaccination can be detected by A2-ELISA, but do not interfere with the LPA-ELISA and DPP diagnostic tests for CVL. Copyright © 2014 Elsevier B.V. All rights reserved.

Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion.

PubMed

Schaal, S M; Kitay, B M; Cho, K S; Lo, T P; Barakat, D J; Marcillo, A E; Sanchez, A R; Andrade, C M; Pearse, D D

2007-01-01

Schwann cell (SC) implantation alone has been shown to promote the growth of propriospinal and sensory axons, but not long-tract descending axons, after thoracic spinal cord injury (SCI). In the current study, we examined if an axotomy close to the cell body of origin (so as to enhance the intrinsic growth response) could permit supraspinal axons to grow onto SC grafts. Adult female Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3 KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral vector encoding enhanced green fluorescent protein (EGFP) were implanted within media into the injury epicenter; injury-only animals served as controls. Animals were tested weekly using the BBB score for 7 weeks postimplantation and received at end point tests for upper body strength: self-supported forelimb hanging, forearm grip force, and the incline plane. Following behavioral assessment, animals were anterogradely traced bilaterally from the reticular formation using BDA-Texas Red. Stereological quantification revealed a twofold increase in the numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in SC implanted animals, corroborating previous reports of their neuroprotective efficacy. Examination of labeled reticulospinal axon growth revealed that while rarely an axon was present within the lesion site of injury-only controls, numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This has not been observed following implantation of SCs alone into the injured thoracic spinal cord. Significant behavioral improvements over injury-only controls in upper limb strength, including an enhanced grip strength (a 296% increase) and an increased self-supported forelimb hanging, accompanied SC-mediated neuroprotection and reticulospinal axon growth. The current study further supports the neuroprotective efficacy of SC implants after SCI and demonstrates that SCs alone are capable of supporting modest supraspinal axon growth when the site of axon injury is closer to the cell body of the axotomized neuron.

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.

Similar mechanisms of traumatic rectal injuries in patients who had anal sex with animals to those who were butt-fisted by human sexual partner.

PubMed

Sendler, Damian Jacob

2017-10-01

Sexual pleasure comes in various forms of physical play, for many it involves stimulation of the vagina, while the anus for others; some enjoy both. A recent report by Cappelletti et al. 1 shows a meta-analysis of cases describing anal trauma due to sexual fisting in human partners. This clinical article reports four cases of males diagnosed with zoophilia, and who received anal sex from animals, resulting in injuries. Surgical and psychiatric evaluations are summarized. Unusual etiology of sexual activity with animals caused peri-anal trauma in men who engaged in anal sex with dogs and farm animals. Injuries to patients who receive anal sex from animals are mechanistically similar to fisting-induced rectal damage. Among zoophiles, the mode of harm occurs through blood-engorged, interlocked penis that causes tissue lacerations upon retraction from an anus. In people experimenting with fisting, repetitive stretching within anal canal and of external sphincter causes the internal injuries. The mode of physical stimulation explains the extent of injuries in fisters vs. zoophiles: in fisting, the pressure applied by hand is controllable proximally around and within anal sphincter, while penetration by the animal penis is unpredictable and occurs within the proximal anal canal. Forensically, the findings presented in this article describe a significant mechanism of injury in fisters versus passive zoophiles. These descriptions may aid in clinically differentiating pleasurable and pathological rectal stimulation. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Influence of olive oil on alveolar bone response during orthodontic retention period: rabbit model study.

PubMed

Al-Hamdany, Afrah K; Al-Khatib, Ali R; Al-Sadi, Hafidh I

2017-08-01

This study attempted to evaluate clinically and histologically the effects of olive oil (Ol) consumption on orthodontic relapse after the retention period. Thirty apparently healthy female albino rabbits, weight more than 1000 g each was used in this study. The animals were grouped randomly into six groups of five animals each: two control and four experimental groups. In control groups, the relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period. In the experimental groups, the animals' groups received Ol, 7.7, or 15.4 ml/kg b.w. per day during the orthodontic retention period. The relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period for each concentration. Modified fixed orthodontic appliances were attached to the rabbits' lower central incisors. Each rabbit received orthodontic intervention for one week, followed by six weeks retention period. At the end of the experiments, the clinical and histological investigations were conducted. Data analyses were performed at the level of p < .05 for the statistically significant difference. Clinically, Ol high concentration four weeks group showed a significantly lower relapse tendency than control four weeks group. Histologically, Ol low concentration zero time group showed significantly higher osteoblasts numbers than control zero time group. Olive oil low and high concentrations four weeks group showed significantly lower fibroblasts count. Moreover, Ol high concentration four weeks group revealed significantly higher bone mineralization, osteoblasts and osteocytes counts than control four weeks study group. Supplementation with Ol during an orthodontic retention period, especially at 15.4 ml/kg b.w. per day concentration, clinically reduced orthodontic relapse on rabbit model. Histologically, Ol increased osteoblasts and osteocytes counts and the relative amount of bone mineralization of connective tissue layer forming alveolar bone (AB) at the end of four weeks after the orthodontic retention period.

Drinking water supplementation with ascorbate is not protective against UVR-B-induced cataract in the guinea pig.

PubMed

Mody, Vino C; Kakar, Manoj; Elfving, Ase; Löfgren, Stefan

2008-03-01

To study if ascorbate supplementation decreases ultraviolet radiation (UVR)-induced cataract development in the guinea pig. Sixty 6-9-week-old pigmented guinea pigs received drinking water supplemented with or without 5.5 mm l-ascorbate for 4 weeks. After supplementation, 40 animals were exposed unilaterally in vivo under anaesthesia to 80 kJ/m(2) UVR-B. One day later, the animals were killed and lenses were extracted. Degree of cataract was quantified by measurement of intensity of forward lens light scattering. Lens ascorbate concentration was determined with high-performance liquid chromatography (HPLC) with UVR detection at 254 nm. Twenty animals were used as non-exposed control. Supplementation increased lens ascorbate concentration significantly. In UVR-exposed animals, mean 95% confidence intervals (CIs) for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.54 +/- 0.07 (no ascorbate) and 0.83 +/- 0.05 (5.5 mm ascorbate). In non-exposed control animals, mean 95% CIs for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.72 +/- 0.12 (0 mm ascorbate) and 0.90 +/- 0.15 (5.5 mm ascorbate). All non-exposed lenses were devoid of cataract. Superficial anterior cataract developed in all UVR-exposed lenses. The lens light scattering was 39.2 +/- 14.1 milli transformed equivalent diazepam concentration (m(tEDC)) without and 35.9 +/- 14.0 m(tEDC) with ascorbate supplementation. Superficial anterior cataract develops in lenses exposed to UVR-B. Ascorbate supplementation is non-toxic to both UVR-B-exposed lenses and non-exposed control lenses. Ascorbate supplementation does not reduce in vivo lens forward light scattering secondary to UVR-B exposure in the guinea pig.

Therapeutic efficacy induced by the oral administration of Agaricus blazei Murill against Leishmania amazonensis.

PubMed

Valadares, Diogo G; Duarte, Mariana C; Ramírez, Laura; Chávez-Fumagalli, Miguel A; Lage, Paula S; Martins, Vivian T; Costa, Lourena E; Ribeiro, Tatiana G; Régis, Wiliam C B; Soto, Manuel; Fernandes, Ana Paula; Tavares, Carlos A P; Coelho, Eduardo A F

2012-10-01

The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dose-titration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg(-1) day(-1)) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological and immunological parameters were analyzed. Mice treated with the AbM presented a 60% reduction in the inflammation of infected footpads as compared to untreated control-infected mice. Moreover, in the treated mice, as compared to the untreated controls, approximately 60 and 66% reductions could be observed in the parasite burdens of the footpad and draining lymph nodes, respectively. In addition, no parasites could be detected in the spleen of treated mice at week 14 postinfection. These treated animals produced significantly higher levels of interferon gamma (IFN-γ) and nitric oxide (NO), higher levels of parasite-specific IgG2a isotype antibodies, and lower levels of interleukin (IL)-4, and IL-10 in the spleen and lymph node cell cultures than did the controls. Differences could be observed by comparing animals treated with AbM to those treated with AmpB, as indicated by a significant reduction in tissue parasitism, higher levels of IFN-γ and NO, and lower levels of IL-4 and IL-10, as well as by a decreased hepatic toxicity. In conclusion, the present study's data show that the A. blazei Murill water extract presents a high potential for the treatment of leishmaniasis, although additional studies on mice, as well as on other mammal hosts, are warranted in an attempt to determine this extract's true efficacy as compared to other known therapeutic products.

Increasing dwell time of mitomycin C in the upper tract with a reverse thermosensitive polymer.

PubMed

Wang, Agnes J; Goldsmith, Zachariah G; Neisius, Andreas; Astroza, Gaston M; Oredein-McCoy, Olugbemisola; Iqbal, Muhammad W; Simmons, W Neal; Madden, John F; Preminger, Glenn M; Inman, Brant A; Lipkin, Michael E; Ferrandino, Michael N

2013-03-01

Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is dependent on adequate contact time of the chemotherapeutic agent with the urothelium. To date, there has not been a reliable method of maintaining this contact for renal or ureteral urothelial carcinoma. We evaluated the safety and feasibility of using a reverse thermosensitive polymer to improve dwell times of mitomycin C (MMC) in the upper tract. Using a porcine model, four animals were treated ureteroscopically with both upper urinary tracts receiving MMC mixed with iodinated contrast. One additional animal received MMC percutaneously. The treatment side had ureteral outflow blocked with a reverse thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and intrarenal pressures measured. Two animals were euthanized immediately, and three animals were euthanized 5 days afterward. In control kidneys, drainage occurred at a mean of 5.3±0.58 minutes. Intrarenal pressures stayed fairly stable: 9.7±14.0 cm H20. In treatment kidneys, dwell time was extended to 60 minutes, when the polymer was washed out. Intrarenal pressures in the treatment kidneys peaked at 75.0±14.7 cm H20 and reached steady state at 60 cm H20. Pressures normalized after washout of the polymer with cool saline. Average washout time was 11.8±9.6 minutes. No histopathologic differences were seen between the control and treatment kidneys, or with immediate compared with delayed euthanasia. A reverse thermosensitive polymer can retain MMC in the upper urinary tract and appears to be safe from our examination of intrarenal pressures and histopathology. This technique may improve the efficacy of topical chemotherapy in the management of upper tract urothelial carcinoma.

Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability

PubMed Central

Arras, Margarete; Rettich, Andreas; Cinelli, Paolo; Kasermann, Hans P; Burki, Kurt

2007-01-01

Background Pain of mild to moderate grade is difficult to detect in laboratory mice because mice are prey animals that attempt to elude predators or man by hiding signs of weakness, injury or pain. In this study, we investigated the use of telemetry to identify indicators of mild-to-moderate post-laparotomy pain. Results Adult mice were subjected to laparotomy, either combined with pain treatment (carprofen or flunixin, 5 mg/kg s/c bid, for 1 day) or without pain relief. Controls received anesthesia and analgesics or vehicle only. Telemetrically measured locomotor activity was undisturbed in all animals, thus confirming that any pain experienced was of the intended mild level. No symptoms of pain were registered in any of the groups by scoring the animals' outer appearance or spontaneous and provoked behavior. In contrast, the group receiving no analgesic treatment after laparotomy demonstrated significant changes in telemetry electrocardiogram recordings: increased heart rate and decreased heart rate variability parameters pointed to sympathetic activation and pain lasting for 24 hours. In addition, core body temperature was elevated. Body weight and food intake were reduced for 3 and 2 days, respectively. Moreover, unstructured cage territory and destroyed nests appeared for 1–2 days in an increased number of animals in this group only. In controls these parameters were not affected. Conclusion In conclusion, real-time telemetric recordings of heart rate and heart rate variability were indicative of mild-to-moderate post-laparotomy pain and could define its duration in our mouse model. This level of pain cannot easily be detected by direct observation. PMID:17683523

Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells.

PubMed

Emerich, Dwaine F; Schneider, Patricia; Bintz, Briannan; Hudak, Jebecka; Thanos, Christopher G

2007-01-01

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3-4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.

Direct Targeting of Macrophages with Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology

PubMed Central

Walker, Joshua A.; Miller, Andrew D.; Burdo, Tricia H.; McGrath, Michael S.; Williams, Kenneth C.

2017-01-01

Background Despite effective combination antiretroviral therapy (cART) HIV infected individuals develop co-morbidities including cardiovascular disease (CVD), where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. Methods We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a SIV infection model of AIDS. Eleven SIV-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 dpi. Animals were time sacrificed (49 dpi), sacrificed when matched placebos controls developed AIDS (63, 70, 77, 80), or at the study endpoint (84 dpi). Aorta, carotid artery and cardiac tissues were analyzed. Quantitative analysis of macrophage populations and T-lymphocytes were done and correlated with cIMT and fibrosis. Results MGBG treatment resulted in a 2.19 (CD163+), 1.86 (CD68+), 2.31 (CD206+), and 2.12-fold (MAC387+) decrease in macrophages in carotid arteries and significant 2.07 (CD163+), 1.61 (CD68+), 1.95 (MAC387+) and 1.62-fold (CD206+) decrease in macrophages in cardiac tissues. CIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and CIMT, and cardiac macrophages and fibrosis was found. Conclusions These data demonstrate directly targeting macrophages with MGBG can reduce cardiovascular inflammation, CIMT, and fibrosis. They suggest therapies targeting macrophages with HIV could be used in conjunction with cART. PMID:28141779

Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.

PubMed

Walker, Joshua A; Miller, Andrew D; Burdo, Tricia H; McGrath, Michael S; Williams, Kenneth C

2017-04-15

Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis. MGBG treatment resulted in 2.19-fold (CD163), 1.86-fold (CD68), 2.31-fold (CD206), and 2.12-fold (MAC387) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163), 1.61-fold (CD68), 1.95-fold (MAC387), and 1.62-fold (CD206) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found. These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

PubMed Central

Grous, Lauren Conova; Vernengo, Jennifer; Jin, Ying; Himes, B. Timothy; Shumsky, Jed S.; Fischer, Itzhak; Lowman, Anthony

2016-01-01

Object In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities. Methods Animals received an implant of either PNIPAAm-g-PEG or PNIPAAm-g-PEG + brain-derived neurotrophic factor (BDNF). The single-pellet reach-to-grasp task and the staircase-reaching task were used to assess skilled motor function associated with reaching and grasping abilities, and the cylinder task was used to assess spontaneous motor function, both before and after injury. Results Because BDNF can stimulate regenerating RST axons, the authors showed that animals receiving an implant of PNIPAAm-g-PEG with codissolved BDNF had an increased recovery rate of fine motor function when compared with a control group (PNIPAAm-g-PEG only) on both a staircase-reaching task at 4 and 8 weeks post-SCI and on a single-pellet reach-to-grasp task at 5 weeks post-SCI. In addition, spontaneous motor function, as measured in the cylinder test, recovered to preinjury values in animals receiving PNIPAAm-g-PEG + BDNF. Fluorescence immunochemistry indicated the presence of both regenerating axons and BDA-labeled fibers growing up to or within the host-graft interface in animals receiving PNIPAAm-g-PEG + BDNF. Conclusions Based on their results, the authors suggest that BDNF delivered by the scaffold promoted the growth of RST axons into the lesion, which may have contributed in part to the increased recovery rate. PMID:23581453

Skin testing of guinea pigs and footpad testing of mice with a new antigen for detecting delayed hypersensitivity to Cryptococcus neoformans.

PubMed

Murphy, J W; Gregory, J A; Larsh, H W

1974-02-01

This study was undertaken to evaluate the potential of a cryptococcal culture filtrate antigen, cryptococcin C184, for detecting delayed hypersensitivity in Cryptococcus neoformans-injected animals. The antigen was tested on guinea pigs which had received saline or C. neoformans and on animals sensitized to Histoplasma capsulatum, Blastomyces dermatitidis, Candida albicans, or Sporothrix schenckii. A delayed-type hypersensitivity response was elicited by cryptococcin C184 in C. neoformans-injected guinea pigs, whereas no indurations or erythemas were seen at 48 h after skin testing of saline controls or heterologously sensitized guinea pigs. Besides being specific for Cryptococcus, the antigen showed a high degree of sensitivity and was reproducible. Footpad tests were conducted with the antigen on mice which had previously received either 10(5) viable C. neoformans cells or saline. Delayed hypersensitivity was indicated in the C. neoformans-injected mice by the increase in thickness of antigen-injected footpads when compared with the saline-injected footpads. In control mice, antigen- and saline-injected footpads were comparable in thickness 24 h after injection. Mice sensitized to B. dermatitidis were footpad tested with C184, and no cross-reactivity was demonstrated.

The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

PubMed Central

Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

2016-01-01

Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

The anti-oxidant effects of ginger and cinnamon on spermatogenesis dys-function of diabetes rats.

PubMed

Khaki, Arash; Khaki, Amir Afshin; Hajhosseini, Laleh; Golzar, Farhad Sadeghpour; Ainehchi, Nava

2014-01-01

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats. Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis. Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05). We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.

Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.

PubMed

Toepp, Angela; Larson, Mandy; Grinnage-Pulley, Tara; Bennett, Carolyne; Anderson, Michael; Parrish, Molly; Fowler, Hailie; Wilson, Geneva; Gibson-Corely, Katherine; Gharpure, Radhika; Cotter, Caitlin; Petersen, Christine

2018-05-01

In Leishmania infantum -endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum , the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec ® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

Effect of science teaching on the young child's concept of piagetian physical causality: Animism and dynamism

NASA Astrophysics Data System (ADS)

Wolfinger, Donna M.

The purpose of this research was to determine whether the young child's understanding of physical causality is affected by school science instruction. Sixty-four subjects, four and one-half through seven years of age, received 300 min of instruction designed to affect the subject's conception of causality as reflected in animism and dynamism. Instruction took place for 30 min per day on ten successive school days. Pretesting was done to allow a stratified random sample to be based on vocabulary level and developmental stage as well as on age and gender. Post-testing consisted of testing of developmental level and level within the causal relations of animism and dynamism. Significant differences (1.05 level) were found between the experimental and control groups for animism. Within the experimental group, males differed significantly (1.001 level) from females. The elimination of animism appeared to have occurred. For dynamism, significant differences (0.05 level) were found only between concrete operational subjects in the experimental and control groups, indicating a concrete level of operations was necessary if dynamism was to be affected. However, a review of interview protocols indicated that subjects classified as nonanimistic had learned to apply a definition rather than to think in a nonanimistic manner.

Use of spineless cactus (Opuntia ficus indica f. inermis) for dairy goats and growing kids: impacts on milk production, kid's growth, and meat quality.

PubMed

Mahouachi, M; Atti, N; Hajji, H

2012-01-01

The objective of this study was to determine the effect of spineless cactus incorporation in food of dairy goats and growing kids on milk production and composition and on kid's growth and meat characteristics. Two experiments were conducted on Tunisian local goats. In the first, 30 females were divided into two groups; goats of Control group were reared on grazing pasture receiving indoor 0.5 kg of hay and 0.4 kg of concentrate. Goats for the second group (Cac-FL) were kept in feedlot and fed cactus ad libitum more 0.5 kg of hay and 0.4 kg of concentrate. In the second experiment, 14 kids were divided into 2 groups receiving 600 g of hay. The Control group received ad libitum a concentrate containing 130 g crude protein (CP) per kg of dry matter. The second group received cactus ad-libitum plus the half concentrate quantity of control one with 260 g CP/kg DM (Cactus). The daily milk production averaged 485 ml for Control group and 407 ml for Cac-FL one. The milk fat content was significantly higher for Control than Cac-FL group. In the second experiment, animals in Control and Cactus groups had similar growth rate. Carcass fat was significantly lower in Cactus than in the Control group. Cactus in the diet was associated with more C18:2 and conjugated linoleic acid as well as a higher proportion of PUFA than Control ones.

Use of Spineless Cactus (Opuntia ficus indica f. inermis) for Dairy Goats and Growing Kids: Impacts on Milk Production, Kid's Growth, and Meat Quality

PubMed Central

Mahouachi, M.; Atti, N.; Hajji, H.

2012-01-01

The objective of this study was to determine the effect of spineless cactus incorporation in food of dairy goats and growing kids on milk production and composition and on kid's growth and meat characteristics. Two experiments were conducted on Tunisian local goats. In the first, 30 females were divided into two groups; goats of Control group were reared on grazing pasture receiving indoor 0.5 kg of hay and 0.4 kg of concentrate. Goats for the second group (Cac-FL) were kept in feedlot and fed cactus ad libitum more 0.5 kg of hay and 0.4 kg of concentrate. In the second experiment, 14 kids were divided into 2 groups receiving 600 g of hay. The Control group received ad libitum a concentrate containing 130 g crude protein (CP) per kg of dry matter. The second group received cactus ad-libitum plus the half concentrate quantity of control one with 260 g CP/kg DM (Cactus). The daily milk production averaged 485 ml for Control group and 407 ml for Cac-FL one. The milk fat content was significantly higher for Control than Cac-FL group. In the second experiment, animals in Control and Cactus groups had similar growth rate. Carcass fat was significantly lower in Cactus than in the Control group. Cactus in the diet was associated with more C18:2 and conjugated linoleic acid as well as a higher proportion of PUFA than Control ones. PMID:22536135

Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

PubMed Central

De Rose, Robert; Fernandez, Caroline S.; Smith, Miranda Z.; Batten, C. Jane; Alcântara, Sheilajen; Peut, Vivienne; Rollman, Erik; Loh, Liyen; Mason, Rosemarie D.; Wilson, Kim; Law, Matthew G.; Handley, Amanda J.; Kent, Stephen J.

2008-01-01

Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans. PMID:18451982

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.

Effect of microthreads on removal torque and bone-to-implant contact: an experimental study in miniature pigs

PubMed Central

Kwon, Yee-Seo; Namgoong, Hee; Kim, Jung-Hoon; Cho, In Hee; Kim, Myung Duk; Eom, Tae Gwan

2013-01-01

Purpose The objective of this study was to evaluate the effect of microthreads on removal torque and bone-to-implant contact (BIC). Methods Twelve miniature pigs for each experiment, a total of 24 animals, were used. In the removal torque analysis, each animal received 2 types of implants in each tibia, which were treated with sandblasting and acid etching but with or without microthreads at the marginal portion. The animals were sacrificed after 4, 8, or 12 weeks of healing. Each subgroup consisted of 4 animals, and the tibias were extracted and removal torque was measured. In the BIC analysis, each animal received 3 types of implants. Two types of implants were used for the removal torque test and another type of implant served as the control. The BIC experiment was conducted in the mandible of the animals. The P1-M1 teeth were extracted, and after a 4-month healing period, 3 each of the 2 types of implants were placed, with one type on each side of the mandible, for a total of 6 implants per animal. The animals were sacrificed after a 2-, 4-, or 8-week healing period. Each subgroup consisted of 4 animals. The mandibles were extracted, specimens were processed, and BIC was analyzed. Results No significant difference in removal torque value or BIC was found between implants with and without microthreads. The removal torque value increased between 4 and 8 weeks of healing for both types of implants, but there was no significant difference between 8 and 12 weeks. The percentage of BIC increased between 2 and 4 weeks for all types of implants, but there was no significant difference between 4 and 8 weeks. Conclusions The existence of microthreads was not a significant factor in mechanical and histological stability. PMID:23508085

Efficacy of albendazole:β-cyclodextrin citrate in the parenteral stage of Trichinella spiralis infection.

PubMed

Codina, Ana V; García, Agustina; Leonardi, Darío; Vasconi, María D; Di Masso, Ricardo J; Lamas, María C; Hinrichsen, Lucila I

2015-01-01

Albendazole-β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis infection in mice. An equimolar complex of ABZ:C-β-CD was prepared by spray-drying and tested in CBi-IGE male mice orally infected with L1 infective larvae. Infected animals were treated with 50 or 30mg/kg albendazole, (ABZ) equivalent amounts of the ABZ:C-β-CD complex and non treated (controls). Mice received a daily dose on days 28, 29 and 30 post-infection. A week later, larval burden and percentage of encysted dead larvae were assessed in the host by counting viable and non-viable larvae in the tongue. Complexation of ABZ with C-β-CD increased the drug dissolution efficiency nearly eightfold. At 37 days p-i, the reduction percentage in muscle larval load was 35% in mice treated with 50mg/kg/day ABZ and 68% in those given the complex. Treatment with the lower dose showed a similar decrease in parasite burden. Treated animals showed a high percentage of nonviable larvae, the proportion being significantly higher in mice receiving the complex than in control animals (72-88% vs. 11%, P=0.0032). These data indicate that ABZ:C-β-CD increases bioavailability and effectiveness of ABZ against encapsulated Trichinella larvae, thus allowing the use of small doses. Copyright © 2015 Elsevier B.V. All rights reserved.

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

PubMed Central

Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

2013-01-01

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning.

PubMed

Basher, A; Rahman, S H; Ghose, A; Arif, S M; Faiz, M A; Dawson, A H

2013-01-01

Acute organophosphorus (OP) poisoning is relatively common and a major cause of death from poisoning in developing countries. Magnesium has been shown to be of benefit in animal models. We conducted a phase II study of bolus doses of (MgSO4) in 50 patients with acute organophosphate poisoning. Patients eligible for inclusion had ingested OP and had cholinergic symptoms consistent with moderate or severe poisoning. All patients received standard care of atropinization titrated to control muscarinic symptoms and pralidoxime. The trial was run in 4 sequential groups of patients. Participants in each group received a different total dose of MgSO4 (20%) administered as intermittent bolus doses infused over 10-15 min or placebo. There was one control patient for every 4 patients who received MgSO4. Group A (16 patients) received a total of 4 gm MgSO4 as a single bolus, group B (8 patients) received 8 gm (in two 4 gm doses q4H), group C (8 patients) received 12 gm (in three 4 gm doses q4H) group D (8 patients) received 16 gm (in four 4 gm doses q4H) and control (10 patients) received placebo). Patients were closely monitored for any adverse reaction like significant clinical neuromuscular disturbance and respiratory depression. No adverse reactions to magnesium were observed. The 24 hour urinary magnesium concentration were statistically different between 16 gm (234.74 ± 74.18 mg/dl) and control (118.06 ± 30.76 mg/dl) (p = 0.019), while it was much lower than the 80% of the intravenous magnesium load. Six patients died in control group compared to 3 in 4 gm, 2 in 8 gm and 1 in 12 gm group. There was no mortality in 16 gm group. Magnesium was well tolerated in this study. Larger studies are required to examine for efficacy.

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)

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

PubMed Central

Sonobe, Takashi; Chenuel, Bruno; Cooper, Timothy K.; Haouzi, Philippe

2015-01-01

Background Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1- describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2- determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity. Methods NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg IV) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7. Results Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB. Conclusion In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats. PMID:26115032

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

PubMed

Sonobe, Takashi; Chenuel, Bruno; Cooper, Timothy K; Haouzi, Philippe

2015-01-01

Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity. NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg i.v.) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7. Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB. In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

Boron supplementation improves bone health of non-obese diabetic mice.

PubMed

Dessordi, Renata; Spirlandeli, Adriano Levi; Zamarioli, Ariane; Volpon, José Batista; Navarro, Anderson Marliere

2017-01-01

Diabetes Mellitus is a condition that predisposes a higher risk for the development of osteoporosis. The objective of this study was to investigate the influence of boron supplementation on bone microstructure and strength in control and non-obese diabetic mice for 30days. The animals were supplemented with 40μg/0,5ml of boron solution and controls received 0,5ml of distilled water daily. We evaluated the biochemical parameters: total calcium, phosphorus, magnesium and boron; bone analysis: bone computed microtomography, and biomechanical assay with a three point test on the femur. This study consisted of 28 animals divided into four groups: Group water control - Ctrl (n=10), Group boron control - Ctrl±B (n=8), Group diabetic water - Diab (n=5) and Group diabetic boron - Diab±B (n=5). The results showed that cortical bone volume and the trabecular bone volume fraction were higher for Diab±B and Ctrl±B compared to the Diab and Ctrl groups (p≤0,05). The trabecular specific bone surface was greater for the Diab±B group, and the trabecular thickness and structure model index had the worst values for the Diab group. The boron serum concentrations were higher for the Diab±B group compared to non-supplemented groups. The magnesium concentration was lower for Diab and Diab±B compared with controls. The biomechanical test on the femur revealed maintenance of parameters of the bone strength in animals Diab±B compared to the Diab group and controls. The results suggest that boron supplementation improves parameters related to bone strength and microstructure of cortical and trabecular bone in diabetic animals and the controls that were supplemented. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effects of the leaf decoction of Momordica charantia (bitter melon) on Mitochondrial Membrane Permeability Transition Pore (MMPTP) and fertility in normal male albino rats.

PubMed

Odewusi, A F; Oyeyemi, M O; Olayemi, F O; Emikpe, B; Ehigie, L O; Adisa, R A; Olorunsogo, O O

2010-12-01

Momordica charantia (M. charantia), a medicinal plant of the family, Cucurbitaceae, is used in treating an array of ailments including diabetes, heamorrhoids, fevers and various cancers. Programmed cell death may be modulated by an intrinsic pathway involving the release of cytochrome C when the mitochondrial membrane permeability transition (MMPTP) pore is opened. Opening of MMPT pore was assayed using the method of Lapidus and Sokolove. The results obtained revealed that there was a dose-dependent and significant increase in the opening of the MMPT pore in rats orally administered the decoction with maximum induction (11-fold increase) at 55mg/100g body weight (bw), although the extent of opening of the pore was reduced at 65mg/100g bw (9-fold increase). An assessment of the blood parameters of animals orally exposed to the decoction showed significant decrease (p<0.05) in lymphocytes and a significant increase (p<0.05) in neutrophils at 55mg/ 100g bw. Moreover, significant increases (p<0.05) in RBC levels at 45 and 65mg/100g bw, were observed. Similarly, PCV and Heamoglobin values were also elevated at 65mg/100g bw while there was a significant reduction (p<0.05) in MCV and MCH values at 45, 55 and 65mg/100g bw. MCHC values were reduced only in animals that received 65mg/ 100g when compared to control animals. Analysis of the spermiogram of the experimental rats showed significant reductions (p<0.05) in sperm motility and sperm cell concentrations for all animals that were orally exposed to the decoction. There was a significant reduction (p<0.05) in percentage viability in animals that received 45mg/100g bw and above. Morphological abnormalities of sperm cells above the proposed percentage range (10%) were also observed in animals that received 45mg/100g bw and above. However, decoction did not show any significant effect on ALT and AST levels but there were significant increases (p<0.05) in a somewhat dose-dependent pattern in ALP and ãGT levels for all groups in comparison to the control group. These findings thus suggest dose-related negative or toxic effects of sub acute (30-day) oral administration of leaf decoction of M. charantia in albino rats and may therefore pose some danger to humans especially in regard to male fertility in individuals who rely on oral administration of the decoction in treating various ailments.

The role of black rice (Oryza sativa L.) in the control of hypercholesterolemia in rats.

PubMed

Salgado, Jocelem Mastrodi; Oliveira, Anderson Giovanni Candido de; Mansi, Débora Niero; Donado-Pestana, Carlos M; Bastos, Candido Ricardo; Marcondes, Fernanda Klein

2010-12-01

Cardiovascular disease is a serious public health problem; it is the first "cause of death" in Brazil and in developed countries. Thus, it is essential to search for alternative sources such as some functional foods to prevent and control the risks of this disease. The purpose of this study was to evaluate the lipidemic parameters in hypercholesterolemic rats fed diets containing black rice variety IAC 600 or unrefined rice. Adult male Wistar rats (Rattus norvegicus var. albinos) were used, weighing about 200-220 g. The animals were divided into four groups: the first received a control casein diet, the second received hypercholesterolemic diet, and the other two groups, after induction of hypercholesterolemia, received the test diets, the first containing 20% black rice and the second 20% unrefined, for 30 days. It was observed that diet containing black rice reduced the level of plasma cholesterol, triglycerides, and low-density lipoprotein. For high-density lipoprotein values, the diet that provided an increase in the levels was the black rice. The diet containing black rice was more effective in controlling the lipidemia in rats compared with the whole rice diet.

Diet enriched with the Amazon fruit açaí (Euterpe oleracea) prevents electrophysiological deficits and oxidative stress induced by methyl-mercury in the rat retina.

PubMed

Brasil, Alódia; Rocha, Fernando Allan de Farias; Gomes, Bruno Duarte; Oliveira, Karen Renata M; de Carvalho, Tayana Silva; Batista, Evander de Jesus O; Borges, Rosivaldo Dos Santos; Kremers, Jan; Herculano, Anderson Manoel

2017-06-01

The protective effect of a diet supplemented by the Amazonian fruit Euterpe oleracea (EO) against methylmercury (MeHg) toxicity in rat retina was studied using electroretinography (ERG) and biochemical evaluation of oxidative stress. Wistar rats were submitted to conventional diet or EO-enriched diet for 28 days. After that, each group received saline solution or 5 mg/kg/day of MeHg for 7 days. Full-field single flash, flash and flicker ERGs were evaluated in the following groups: control, EO, MeHg, and EO+MeHg. The amplitudes of the a-wave, b-wave, photopic negative response from rod and/or cone were measured by ERGs as well as the amplitudes and phases of the fundamental component of the sine-wave flicker ERG. Lipid peroxidation was determined by thiobarbituric acid reactive species. All ERG components had decreased amplitudes in the MeHg group when compared with controls. EO-enriched food had no effect on the non-intoxicated animals. The intoxicated animals and those that received the supplemented diet presented significant amplitude reductions of the cone b-wave and of the fundamental flicker component when compared with non-intoxicated control. The protective effect of the diet on scotopic conditions was only observed for bright flashes eliciting a mixed rod and cone response. There was a significant increase of lipid peroxidation in the retina from animals exposed to MeHg and EO-supplemented diet was able to prevent MeHg-induced oxidative stress in retinal tissue. These findings open up perspectives for the use of diets supplemented with EO as a protective strategy against visual damage induced by MeHg.

Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats

PubMed Central

Nayak, BS; Pinto Pereira, Lexley M

2006-01-01

Background Catharanthus roseus L (C. roseus) has been used to treat a wide assortment of diseases including diabetes. The objective of our study was to evaluate the antimicrobial and wound healing activity of the flower extract of Catharanthus in rats. Methods Wound healing activity was determined in rats, after administration (100 mg kg-1 day-1) of the ethanol extract of C. roseus flower, using excision, incision and dead space wounds models. The animals were divided into two groups of 6 each in all the models. In the excision model, group 1 animals were topically treated with carboxymethyl cellulose as placebo control and group 2 received topical application of the ethanol extract of C. roseus at a dose of 100 mg/kg body weight/day. In an incision and dead space model group 1 animals were given normal saline and group 2 received the extract orally at a dose of 100 mg kg-1 day-1. Healing was assessed by the rate of wound contraction, period of epithelization, tensile strength (skin breaking strength), granulation tissue weight, and hydoxyproline content. Antimicrobial activity of the flower extract against four microorganisms was also assessed Results The extract of C. roseus significantly increased the wound breaking strength in the incision wound model compared with controls (P < 0.001). The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly increased in comparison to control wounds (P < 0.001), Wet and dry granulation tissue weights, and hydroxyproline content in a dead space wound model increased significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus demonstrated sensitivity to C. roseus Conclusion Increased wound contraction and tensile strength, augmented hydroxyproline content along with antimicrobial activity support the use of C. roseus in the topical management of wound healing. PMID:17184528

Instrument-assisted cross-fiber massage accelerates knee ligament healing.

PubMed

Loghmani, M Terry; Warden, Stuart J

2009-07-01

Controlled laboratory study. To investigate the effects of instrument-assisted cross-fiber massage (IACFM) on tissue-level healing of knee medial collateral ligament (MCL) injuries. Ligament injuries are common and significant clinical problems for which there are few established interventions. IACFM represents an intervention that may mediate tissue-level healing following ligament injury. Bilateral knee MCL injuries were created in 51 rodents, while 7 rodents were maintained as ligament-intact, control animals. IACFM was commenced 1 week following injury and introduced 3 sessions per week for 1 minute per session. IACFM was introduced unilaterally (IACFM-treated), with the contralateral, injured MCL serving as an internal control (nontreated). Thirty-one injured animals received 9 ACFM treatments, while the remaining 20 injured animals received 30 treatments. Ligament biomechanical properties and morphology were assessed at either 4 or 12 weeks postinjury. IACFM-treated ligaments were 43.1% stronger (P<.05), 39.7% stiffer (P<.01), and could absorb 57.1% more energy before failure (P<.05) than contralateral, injured, nontreated ligaments at 4 weeks postinjury. On histological and scanning electron microscopy assessment, IACFM-treated ligaments appeared to have improved collagen fiber bundle formation and orientation within the scar region than nontreated ligaments. There were minimal differences between IACFM-treated and contralateral, nontreated ligaments at 12 weeks postinjury, although IACFM-treated ligaments were 15.4% stiffer (P<.05). IACFM-accelerated ligament healing, possibly via favorable effects on collagen formation and organization, but had minimal effect on the final outcome of healing. These findings are clinically interesting, as there are few established interventions for ligament injuries, and IACFM is a simple and practical therapy technique. J Orthop Sports Phys Ther 2009;39(7):506-514, Epub 24 February 2009. doi:10.2519/jospt.2009.2997.

Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model

PubMed Central

Tessaro, Irene; Modina, Silvia; Lodde, Valentina; Sivelli, Giulia; Franciosi, Federica; Terzaghi, Laura; Luchini, Patrizia; Rumio, Cristiano; Luciano, Alberto Maria

2017-01-01

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested. Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant. Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05 vs. control group) and reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone treatment). Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment. PMID:29062793

Short-term fasting, seizure control and brain amino acid metabolism.

PubMed

Yudkoff, Marc; Daikhin, Yevgeny; Nissim, Ilana; Horyn, Oksana; Luhovyy, Bogdan; Lazarow, Adam; Nissim, Itzhak

2006-01-01

The ketogenic diet is an effective treatment for seizures, but the mechanism of action is unknown. It is uncertain whether the anti-epileptic effect presupposes ketosis, or whether the restriction of calories and/or carbohydrate might be sufficient. We found that a relatively brief (24 h) period of low glucose and low calorie intake significantly attenuated the severity of seizures in young Sprague-Dawley rats (50-70 gms) in whom convulsions were induced by administration of pentylenetetrazole (PTZ). The blood glucose concentration was lower in animals that received less dietary glucose, but the brain glucose level did not differ from control blood [3-OH-butyrate] tended to be higher in blood, but not in brain, of animals on a low-glucose intake. The concentration in brain of glutamine increased and that of alanine declined significantly with low-glucose intake. The blood alanine level fell more than that of brain alanine, resulting in a marked increase ( approximately 50%) in the brain:blood ratio for alanine. In contrast, the brain:blood ratio for leucine declined by about 35% in the low-glucose group. When animals received [1-(13)C]glucose, a metabolic precursor of alanine, the appearance of (13)C in alanine and glutamine increased significantly relative to control. The brain:blood ratio for [(13)C]alanine exceeded 1, indicating that the alanine must have been formed in brain and not transported from blood. The elevated brain(alanine):blood(alanine) could mean that a component of the anti-epileptic effect of low carbohydrate intake is release of alanine from brain-to-blood, in the process abetting the disposal of glutamate, excess levels of which in the synaptic cleft would contribute to the development of seizures.

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

PubMed

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

2013-12-01

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

Effects of intraaortic balloon augmentation in a porcine model of endotoxemic shock.

PubMed

Engoren, Milo; Habib, Robert H

2004-03-01

Patients with septic shock commonly have myocardial dysfunction associated with lactic acid production and troponin I release. The purpose of this study was to evaluate the effects on intraaortic balloon pump (IABP) support on myocardial dysfunction. Prospective, randomized controlled study. Animal research laboratory. Ten pigs had arterial, pulmonary arterial, and coronary catheters inserted. After receiving endotoxin infusion over 30 min, half the animals received IABP support. Coronary sinus lactic acid levels (P< 0.05 for both 90 min versus baseline and 60 min versus baseline) and arterial lactic acid levels (P < 0.05 for both 90 min versus baseline and 60 min versus baseline) increased with time but did not differ between IABP and sham groups. While overall there was no difference with time in myocardial lactic acid consumption or production (calculated as arterial lactic acid level minus coronary sinus lactic acid level), the IABP group showed net myocardial lactic acid consumption at 90 min, while the sham group showed myocardial lactic acid production. Three of five animals in each group showed troponin I release. The levels were similar and did not differ between groups. IABP had no benefits in this porcine model of endotoxemic shock.

Periodontal regeneration using engineered bone marrow mesenchymal stromal cells.

PubMed

Yang, Yi; Rossi, Fabio M V; Putnins, Edward E

2010-11-01

Regeneration of lost periodontium is a challenge in that both hard (alveolar bone, cementum) and soft (periodontal ligament) connective tissues need to be restored to their original architecture. Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connective tissue regeneration. We hypothesized that BM-MSCs are able to sense biological cues from the local microenvironment and organize appropriately to contribute to the regeneration of both soft and hard periodontal connective tissues. To test this hypothesis, we transplanted GFP(+) rat BM-MSCs expanded ex vivo on microcarrier gelatin beads into a surgically created rat periodontal defect. After three weeks, evidence of regeneration of bone, cementum and periodontal ligament was observed in both transplanted and control animals. However, the animals that received BM-MSCs regenerated significantly greater new bone. In addition, the animals that had received the cells and beads transplant had significantly more appropriately orientated periodontal ligament fibers, indicative of functional restoration. Finally, donor-derived BM-MSCs were found integrated in newly formed bone, cementum and periodontal ligament, suggesting that they can directly contribute to the regeneration of cells of these tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Biosonar performance of foraging Blainvilles beaked whales (Mesoplodon densirostris)

NASA Astrophysics Data System (ADS)

Madsen, Peter T.; Johnson, Mark; Tyack, Peter L.; Aguilar de Soto, Natacha; Zimmer, Walter M. X.

2004-05-01

Echolocating animals like bats and toothed whales navigate and locate food by means of echoes from sounds transmitted by the animals themselves. Toothed whale echolocation has been studied intensively in captivity, but little information exists on how echolocation is used by wild animals for orientation and prey location. To expand on this issue, a noninvasive, acoustic Dtag (96-kHz sampling, 16-bit resolution) was deployed on two Blainvilles beaked whales. The tagged whales only clicked at depths below 200 m during deep foraging dives. The echolocation clicks are directional, 250-ms transients with peak energy in the 30-40-kHz band. Echoes from the seafloor and from prey items were recorded. The regular click rate is not adjusted to the decreasing echo delay from incoming prey until the target is within an approximate body length of the whale after which the click rate is increased rapidly akin to the buzz phase of echolocating bats. This suggests that the whales use different sonar strategies for operating in near versus far field modes. Changes in received echo intensities from prey targets during approaches are compared to the active gain control in the receiving system of bats and in the transmitting system of dolphins.

Lessons with Living Harvest Mice: An empirical study of their effects on intrinsic motivation and knowledge acquisition

NASA Astrophysics Data System (ADS)

Wilde, Matthias; Hußmann, Jona Samuel; Lorenzen, Simone; Meyer, Annika; Randler, Christoph

2012-12-01

The aim of this study was to evaluate the effects of living animals on pupils' intrinsic motivation and knowledge. Various studies from the late 1970s and 1980s stress the high effectiveness of authentic learning experiences in pupils' knowledge acquisition. However, there are only few current empirical studies on this topic. The research question of our study is to assess whether the use of living animals in the biology classroom supports intrinsic motivation and knowledge acquisition. In a pre-/post-test design, 185 fifth graders received two different treatments: the experimental group (N = 74) was taught with living harvest mice (Micromys minutus) and the control group (N = 111) received lessons with the same content which was presented in short film clips on laptop computers. Knowledge acquisition was assessed with open-ended and closed questions, while intrinsic motivation was tested with an adapted version of the Intrinsic Motivation Inventory (IMI). There were no differences in knowledge acquisition between the treatments. However, the results of the IMI showed significant differences in favour of the experimental group in interest/enjoyment, perceived competence, and perceived autonomy. Thus, living animals exert a positive influence on motivation.

Evaluation of a closed loop inductive power transmission system on an awake behaving animal subject.

PubMed

Kiani, Mehdi; Kwon, Ki Yong; Zhang, Fei; Oweiss, Karim; Ghovanloo, Maysam

2011-01-01

This paper presents in vivo experimental results for a closed loop wireless power transmission system to implantable devices on an awake behaving animal subject. In this system, wireless power transmission takes place across an inductive link, controlled by a commercial off-the-shelf (COTS) radio frequency identification (RFID) transceiver (TRF7960) operating at 13.56 MHz. Induced voltage on the implantable secondary coil is rectified, digitized by a 10-bit analog to digital converter, and transmitted back to the primary via back telemetry. Transmitter (Tx) and receiver (Rx) circuitry were mounted on the back of an adult rat with a nominal distance of ~7 mm between their coils. Our experiments showed that the closed loop system was able to maintain the Rx supply voltage at the designated 3.8 V despite changes in the coils' relative distance and alignment due to animal movements. The Tx power consumption changed between 410 ~ 560 mW in order to deliver 27 mW to the receiver. The open loop system, on the other hand, showed undesired changes in the Rx supply voltage while the Tx power consumption was constant at 660 mW.

A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats.

PubMed

Morato, P N; Lollo, P C B; Moura, C S; Batista, T M; Carneiro, E M; Amaya-Farfan, J

2013-08-15

Whey protein hydrolysate (WPH) is capable of increasing muscle glycogen reserves and of concentrating the glucose transporter in the plasma membrane (PM). The objective of this study was to determine which WPH components could modulate translocation of the glucose transporter GLUT-4 to the PM of animal skeletal muscle. Forty-nine animals were divided into 7 groups (n=7) and received by oral gavage 30% glucose plus 0.55 g/kg body mass of the following WPH components: (a) control; (b) WPH; (c) L-isoleucine; (d) L-leucine; (e) L-leucine plus L-isoleucine; (f) L-isoleucyl-L-leucine dipeptide; (g) L-leucyl-L-isoleucine dipeptide. After receiving these solutions, the animals were sacrificed and the GLUT-4 analysed by western blot. Additionally, glycogen, glycaemia, insulin and free amino acids were also determined by standard methods. Of the WPH components tested, the amino acid L-isoleucine and the peptide L-leucyl-L-isoleucine showed greater efficiency in translocating GLUT-4 to the PM and of increasing glucose capture by skeletal muscle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy studies of Reactive Skin Decontamination Lotion, M291 Skin Decontamination Kit, 0.5% bleach, 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents, part 1: guinea pigs challenged with VX.

PubMed

Braue, Ernest H; Smith, Kelly H; Doxzon, Bryce F; Lumpkin, Horace L; Clarkson, Edward D

2011-03-01

This report, first in a series of five, directly compares the efficacy of 4 decontamination products and Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA) in the haired guinea pig model following exposure to VX. In all experiments, guinea pigs were close-clipped and given anesthesia. In the decontamination experiments, the animals were challenged with VX and decontaminated after a 2-minute delay for the standard procedure or at longer times for the delayed-decontamination experiments. Skin Exposure Reduction Paste Against Chemical Warfare Agents was applied as a thin coating (0.1 mm thick), allowed to dry for 15 minutes, and challenged with VX. After a 2-hour challenge, any remaining VX was blotted off the animal, but no additional decontamination was done. Positive control animals were challenged with VX in the same manner as the treated animals, except that they received no treatment. In addition, the positive control animals were always challenged with 5% VX in isopropyl alcohol (IPA) solution, whereas the treatment animals received either neat (undiluted) VX or 5% VX in IPA solution. All animals were observed during the first 4 hours and again at 24 hours after exposure for signs of toxicity and death. The protective ratio (PR, defined as the median lethal dose [LD(50)] of the treatment group divided by the LD(50) of the untreated positive control animals) was calculated from the probit dose-response curves established for each treatment group and nontreated control animals. Significance in this report was defined as p < .05. In the standard 2-minute neat VX decontamination experiments, the calculated PRs for Reactive Skin Decontamination Lotion (RSDL), 0.5% bleach, 1% soapy water, and the M291 Skin Decontamination Kit (SDK) were 66, 17, 16, and 1.1, respectively. Reactive Skin Decontamination Lotion was by far the most effective decontamination product tested and was significantly better than any of the other products. Bleach and soapy water provided equivalent and good (PR > 5) protection. They were both significantly better than the M291 SDK. The M291 SDK did not provide significant protection compared with positive controls. In the neat VX delayed-decontamination experiments, the calculated LT(50) (the delayed-decontamination time at which 50% of the animals died in the test population following a 5-LD(50) challenge) values for RSDL, 0.5% bleach, and 1% soapy water were 31, 48, and 26 minutes, respectively. The results showed that SERPACWA provided significant, but modest (PR < 5), protection against neat VX, with a PR of 2.1. Several conclusions can be drawn from this study: 1) RSDL provided superior protection against VX compared with the other products tested; 2) 0.5% bleach and 1% soapy water were less effective than RSDL, but still provided good protection against VX; 3) the M291 SDK was the least effective decontamination product and did not provide significant protection against VX; 4) the agent was observed to streak when using the M291 SDK, and efficacy may improve if the agent is first blotted, followed by wiping with a new or clean part of the M291 SDK pad; 5) RSDL, 0.5% bleach, and 1% soapy water provided significant protection against a 5-LD(50) challenge of VX, even when decontamination was delayed for up to about 30 minutes; and 6) SERPACWA provided significant, but modest, protection against VX.

Familiarity to a Feed Additive Modulates Its Effects on Brain Responses in Reward and Memory Regions in the Pig Model

PubMed Central

Val-Laillet, David; Meurice, Paul; Clouard, Caroline

2016-01-01

Brain responses to feed flavors with or without a feed additive (FA) were investigated in piglets familiarized or not with this FA. Sixteen piglets were allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI) received a standard control feed and the familiarized group (FAM) received the same feed added with a FA mainly made of orange extracts. Animals were subjected to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16 and d 23. Production traits of the piglets were assessed up to d 28 post-weaning. From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission tomography of 18FDG) under anesthesia to investigate the brain activity triggered by the exposure to the flavors of the feed with (FA) or without (C) the FA. Images were analyzed with SPM8 and a region of interest (ROI)-based small volume correction (p < 0.05, k ≥ 25 voxels per cluster). The brain ROI were selected upon their role in sensory evaluation, cognition and reward, and included the prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus striatum. The FAM animals showed a moderate preference for the novel post-transition FA feed compared to the C feed on d 16, i.e., day of the feed transition (67% of total feed intake). The presence or absence of the FA in the diet from weaning had no impact on body weight, average daily gain, and feed efficiency of the animals over the whole experimental period (p ≥ 0.10). Familiar feed flavors activated the prefrontal cortex. The amygdala, insular cortex, and prepyriform area were only activated in familiarized animals exposed to the FA feed flavor. The perception of FA feed flavor in the familiarized animals activated the dorsal striatum differently than the perception of the C feed flavor in naive animals. Our data demonstrated that the perception of FA in familiarized individuals induced different brain responses in regions involved in reward anticipation and/or perception processes than the familiar control feed flavor in naive animals. Chronic exposure to the FA might be necessary for positive hedonic effects, but familiarity only cannot explain them. PMID:27610625

Social Behavior in Interacting Squirrel Monkeys with Differential Nutritional and Environmental Histories.

ERIC Educational Resources Information Center

Chappell, Patricia F.

This paper reports an observational study of the effects of handling on the social behavior of squirrel monkeys who received a protein deficient diet. After birth, experimental animals received a low-protein diet for a 6-week period. A subgroup of these animals were handled between 3 and 12 weeks of age. All of the animals interacted (in four…

Estradiol therapy in adulthood reverses glial and neuronal alterations caused by perinatal asphyxia.

PubMed

Saraceno, Gustavo Ezequiel; Bertolino, María Laura Aón; Galeano, Pablo; Romero, Juan Ignacio; Garcia-Segura, Luis Miguel; Capani, Francisco

2010-06-01

The capacity of the ovarian hormone 17beta-estradiol to prevent neurodegeneration has been characterized in several animal models of brain and spinal cord pathology. However, the potential reparative activity of the hormone under chronic neurodegenerative conditions has received less attention. In this study we have assessed the effect of estradiol therapy in adulthood on chronic glial and neuronal alterations caused by perinatal asphyxia (PA) in rats. Four-month-old male Sprague-Dawley rats submitted to PA just after delivery, and their control littermates, were injected for 3 consecutive days with 17beta estradiol or vehicle. Animals subjected to PA and treated with vehicle showed an increased astrogliosis, focal swelling and fragmented appearance of MAP-2 immunoreactive dendrites, decreased MAP-2 immunoreactivity and decreased phosphorylation of high and medium molecular weight neurofilaments in the hippocampus, compared to control animals. Estradiol therapy reversed these alterations. These findings indicate that estradiol is able to reduce, in adult animals, chronic reactive astrogliosis and neuronal alterations caused by an early developmental neurodegenerative event, suggesting that the hormone might induce reparative actions in the Central Nervous System (CNS). Copyright (c) 2009 Elsevier Inc. All rights reserved.

Implantation of a Novel Biologic and Hybridized Tissue Engineered Bioimplant in Large Tendon Defect: An In Vivo Investigation

PubMed Central

Oryan, Ahmad; Moshiri, Ali; Parizi, Abdolhamid Meimandi

2014-01-01

Surgical reconstruction of large Achilles tendon defects is technically demanding. There is no standard method, and tissue engineering may be a valuable option. We investigated the effects of 3D collagen and collagen-polydioxanone sheath (PDS) implants on a large tendon defect model in rabbits. Ninety rabbits were divided into three groups: control, collagen, and collagen-PDS. In all groups, 2 cm of the left Achilles tendon were excised and discarded. A modified Kessler suture was applied to all injured tendons to retain the gap length. The control group received no graft, the treated groups were repaired using the collagen only or the collagen-PDS prostheses. The bioelectrical characteristics of the injured areas were measured at weekly intervals. The animals were euthanized at 60 days after the procedure. Gross, histopathological and ultrastructural morphology and biophysical characteristics of the injured and intact tendons were investigated. Another 90 pilot animals were also used to investigate the inflammatory response and mechanism of graft incorporation during tendon healing. The control tendons showed severe hyperemia and peritendinous adhesion, and the gastrocnemius muscle of the control animals showed severe atrophy and fibrosis, with a loose areolar connective tissue filling the injured area. The tendons receiving either collagen or collagen-PDS implants showed lower amounts of peritendinous adhesion, hyperemia and muscle atrophy, and a dense tendon filled the defect area. Compared to the control tendons, application of collagen and collagen-PDS implants significantly improved water uptake, water delivery, direct transitional electrical current and tissue resistance to direct transitional electrical current. Compared to the control tendons, both prostheses showed significantly increased diameter, density and alignment of the collagen fibrils and maturity of the tenoblasts at ultrastructure level. Both prostheses influenced favorably tendon healing compared to the control tendons, with no significant differences between collagen and collagen-PDS groups. Implantation of the 3D collagen and collagen-PDS implants accelerated the production of a new tendon in the defect area, and may become a valuable option in clinical practice. PMID:24004331

Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model.

PubMed

Xanthos, Theodoros; Psichalakis, Nikolaos; Russell, David; Papalois, Apostolos; Koutsovasilis, Anastasios; Athanasopoulos, Dimitrios; Gkiokas, Georgios; Chalkias, Athanasios; Iacovidou, Nicoletta

2016-08-01

To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS. Copyright © 2016 Elsevier Inc. All rights reserved.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

PubMed

Mortazavi, S M J; Rahimi, S; Mosleh-Shirazi, M A; Arjomandi, M; Soleimani, A; Koohi Hossein-Abadi, O; Haghani, M; Alavi, M

2015-06-01

Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

NASA Technical Reports Server (NTRS)

Cheung, E. V.; Tidball, J. G.

2003-01-01

OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits.

PubMed

Lee, Jaebum; Sieweke, Janet H; Rodriguez, Nancy A; Schüpbach, Peter; Lindström, Håkan; Susin, Cristiano; Wikesjö, Ulf M E

2009-07-01

The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration. Proprietary nano-technology surface-modified (calcium phosphate: CaP) micro-structured zirconia implants (A and C), control micro-structured zirconia implants (ZiUnite), and titanium porous oxide implants (TiUnite) were implanted into the femoral condyle in 40 adult male New Zealand White rabbits. Each animal received one implant in each hind leg; thus, 20 animals received A and C implants and 20 animals received ZiUnite and TiUnite implants in contralateral hind legs. Ten animals/group were euthanized at weeks 3 and 6 when biopsies of the implant sites were processed for histometric analysis using digital photomicrographs produced using backscatter scanning electron microscopy. The TiUnite surface demonstrated significantly greater bone-implant contact (BIC) (77.6+/-2.6%) compared with the A (64.6+/-3.6%) and C (62.2+/-3.1%) surfaces at 3 weeks (p<0.05). Numerical differences between ZiUnite (70.5+/-3.1%) and A and C surfaces did not reach statistical significance (p>0.05). Similarly, there were non-significant differences between the TiUnite and the ZiUnite surfaces (p>0.05). At 6 weeks, there were no significant differences in BIC between the TiUnite (67.1+/-4.2%), ZiUnite (69.7+/-5.7%), A (68.6+/-1.9%), and C (64.5+/-4.1%) surfaces (p>0.05). TiUnite and ZiUnite implant surfaces exhibit high levels of osseointegration that, in this model, confirm their advanced osteoconductive properties. Addition of CaP nano-technology to the ZiUnite surface does not enhance the already advanced osteoconductivity displayed by the TiUnite and ZiUnite implant surfaces.

Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction.

PubMed

Pires, María J; Rodríguez-Peña, Ana B; Arévalo, Miguel; Cenador, Begoña; Evangelista, Stefano; Esteller, Alejandro; Sánchez-Rodríguez, Angel; Colaço, Aura; López-Novoa, José M

2007-12-01

D/L-Nebivolol is a lypophilic beta1-adrenergic antagonist which is devoid of intrinsic sympathomimetic activity and can increase nitric oxide (NO) bioavailability with its subsequent vasodilating properties. The purpose of the present work was to assess the effect of long-term nebivolol administration on both renal damage and endothelial dysfunction induced by renal mass reduction (RMR) in rats. Atenolol, which does not increase NO bioavailability, was included in the study as a comparative beta-adrenoceptor antagonist. Rats were subjected to both right nephrectomy and surgical removal of two-thirds of the left kidney in order to retain approximately one-sixth of the total renal mass. One week after ablation, rats were distributed randomly according to the following experimental groups: control group containing RMR rats without treatment; RMR rats treated daily with nebivolol for 6 months (drinking water, 8 mg/kg per day); and RMR rats treated daily with atenolol for 6 months (drinking water, 80 mg/kg per day). A group of sham-operated animals was also included. Administration of either nebivolol or atenolol similarly reduced arterial pressure in comparison with RMR untreated animals; however, animals receiving nebivolol presented lower levels of collagen type I expression as well as lower glomerular and interstitial fibrosis than those receiving atenolol. Urinary excretion of oxidative stress markers were also lower in animals receiving nebivolol than in rats treated with atenolol. Furthermore, nebivolol prevented RMR-induced endothelial dysfunction more efficiently than atenolol. Nebivolol protects against renal fibrosis, oxidative stress and endothelial dysfunction better than equivalent doses, in terms of arterial pressure reduction, of atenolol in a hypertensive model of renal damage induced by RMR.

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

USGS Publications Warehouse

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

2006-01-01

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

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats.

PubMed

Rudeen, P K; Hagaman, J

1988-08-15

Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.

Measuring the Effects of an Animal-Assisted Intervention for Pediatric Oncology Patients and Their Parents: A Multisite Randomized Controlled Trial [Formula: see text].

PubMed

McCullough, Amy; Ruehrdanz, Ashleigh; Jenkins, Molly A; Gilmer, Mary Jo; Olson, Janice; Pawar, Anjali; Holley, Leslie; Sierra-Rivera, Shirley; Linder, Deborah E; Pichette, Danielle; Grossman, Neil J; Hellman, Cynthia; Guérin, Noémi A; O'Haire, Marguerite E

2018-05-01

This multicenter, parallel-group, randomized trial examined the effects of an animal-assisted intervention on the stress, anxiety, and health-related quality of life for children diagnosed with cancer and their parents. Newly diagnosed patients, aged 3 to 17 years (n = 106), were randomized to receive either standard care plus regular visits from a therapy dog (intervention group), or standard care only (control group). Data were collected at set points over 4 months of the child's treatment. Measures included the State-Trait Anxiety Inventory™, Pediatric Quality of Life Inventory, Pediatric Inventory for Parents, and child blood pressure and heart rate. All instruments were completed by the child and/or his/her parent(s). Children in both groups experienced a significant reduction in state anxiety ( P < .001). Parents in the intervention group showed significantly decreased parenting stress ( P = .008), with no changes in stress among parents in the control group. However, no significant differences between groups over time on any measures were observed. Animal-assisted interventions may provide certain benefits for parents and families during the initial stages of pediatric cancer treatment.

Stimulation of the basolateral amygdala improves the acquisition of a motor skill.

PubMed

Bergado, Jorge A; Rojas, Yeneissy; Capdevila, Vladimir; González, Odalys; Almaguer-Melian, William

2006-01-01

We have previously shown that the stimulation of limbic structures related to affective life such as the amygdale can improve and reinforce neural plastic processes related to hippocampus-dependent forms of explicit memory, as spatial memory and LTP. We now assessed whether this effect is restricted to the mentioned structure and memory type, or represents a more general form of modulatory influence. Young, male Sprague Dawley rats were implanted stereotactically with one electrode in the basolateral amygdala (BLA) and trained to acquire a motor skill using their right anterior limb. A group of animals received 3 trains of 15 impulses at the BLA 15 minutes after each daily training session. A second group of implanted animals was handled in the same way, but not stimulated, while a third group was not implanted. After reaching the training criterion the left motor cortex was mapped by the observation of the movements induced by stimuli applied in discrete points of the cortex. Cortical representation of the anterior limb was increased in all trained animals, showing that the motor cortex is involved in the acquisition of the new skill. Animals receiving stimulation of the BLA showed similar cortical changes, but learned faster than non-stimulated controls. Reinforcement of neural plasticity by the activation of the amygdala is not restricted to hippocampus-dependent explicit memory, but it might represent a universal mechanism to modulate plasticity.

Effect of Ranitidine on Acetaminophen-Induced Hepatotoxicity in Dogs

PubMed Central

Panella, C.; Makowka, L.; Barone, M.; Polimeno, L.; Rizzi, S.; Demetris, J.; Bell, S.; Guglielmi, F. W.; Prelich, J. G.; Van Thiel, D. H.; Starzl, T. E.; Francavilla, A.

2010-01-01

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose–response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals. PMID:2307085

Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

PubMed

Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

2013-01-01

We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

Bactericidal micron-thin sol-gel films prevent pin tract and periprosthetic infection.

PubMed

Qu, Haibo; Knabe, Christine; Burke, Megan; Radin, Shula; Garino, Jonathan; Schaer, Thomas; Ducheyne, Paul

2014-08-01

Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent conflicts. The risk of infection is considerable with fracture fixation devices. In this pilot study, we examined the use of unique bactericidal micron-thin sol-gel films on fracture fixation devices and their ability to prevent and eradicate infections. External fixation was studied with micron-thin sol-gel coated percutaneous pins releasing triclosan and inserted medially into rabbit tibiae. A total of 11 rabbits received percutaneous pins that were either uncoated or sol-gel/triclosan coated. Internal fracture fixation was also studied using sol-gel coated intramedullary (IM) nails releasing vancomycin in the intramedullary tibiae. Six sheep received IM nails that were coated with a sol-gel film that either contained vancomycin or did not contain vancomycin. All animals were challenged with Staphylococcus aureus around the implant. Animals were euthanized at 1 month postoperative. Rabbits receiving triclosan/sol-gel coated percutaneous pins did not show signs of infection. Uncoated percutaneous pins had a significantly higher infection rate. In the sheep study, there were no radiographic signs of osteomyelitis with vancomycin/sol-gel coated IM nails, in contrast to the observations in the control cohort. Hence, the nanostructured sol-gel controlled release technology offers the promise of a reliable and continuous delivery system of bactericidals from orthopedic devices to prevent and treat infection. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

[Effect of acetylsalicylic acid on the reproductive performance and on offspring from wistar rats].

PubMed

Damasceno, Débora Cristina; Volpato, Gustavo Tadeu; Person, Osmar Clayton; Yoshida, Alessandra; Rudge, Marilza Vieira Cunha; Calderon, Iracema de Mattos Paranhos

2002-01-01

The aim of this paper was to perform a randomized, controlled and blinded study to investigate if a therapeutic dose of acetylsalicylic acid (ASA), taken by pregnant women, may also cause embryotoxic or congenital abnormalities on experimental animal. Females were confirmed to have mated by observations of sperm in a vaginal smear. The day on which spermatozoa were found in the vaginal smear was considered as day 1 of gestation (GD1). After randomization, mated females were assigned to experimental groups and individually caged, were given 50 mg/kg/day of acetylsalicylic acid, by needle gavage once daily, during two different periods of pregnancy. One group of dams (n=11) received aspirin from day 1 to 4 of pregnancy (before embryonic implantation) for evaluation of the blastocysts, and another group received aspirin from day 6 to 15 of pregnancy (organogenic period) for fetal evaluation. Control groups (n=12) received distilled water in same volume and during same periods as their respective experimental groups. The treatment of the dams with ASA, according to minimal therapeutic dose used for humans, did not cause embryotoxic or major malformations on experimental animal but was responsible for rate increased of fetuses presenting ureteric dilatation. After analysis of the data, it appears that, although direct conclusive evidence of adverse effects in humans is lacking, a potential hazard dose exists and thus the indiscriminate use of acetylsalicylic acid (aspirin) is contraindicated.

Functional and physiological effects of treadmill training induced by buspirone, carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.

PubMed

Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

2012-05-01

Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss. The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures. Induced locomotor movement, adipose tissue, skeletal muscle, and femoral bone properties were compared in unoperated control mice, operated controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice (Tx + BCD, Tx + BCD + clenbuterol) that also received training. BCD- and BCD + clenbuterol-treated mice showed comparable levels of locomotor movements that significantly improved over time. Soleus muscle mass and soleus and extensor digitorum longus cross-sectional area significantly increased in both groups of BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals. Fiber type conversion, adipose tissues, bone mineral density, and content were reduced in all Tx groups compared with unoperated control mice. These findings suggest that locomotor movement and muscle properties can be restored to near-normal levels after several weeks of BCD treatment, regular training, and clenbuterol in completely paraplegic animals.

Biological control of Ascaris suum eggs by Pochonia chlamydosporia fungus.

PubMed

Ferreira, Sebastião Rodrigo; de Araújo, Jackson Victor; Braga, Fábio Ribeiro; Araujo, Juliana Milani; Frassy, Luiza Neme; Ferreira, Aloízio Soares

2011-12-01

Ascaris suum is a gastrointestinal nematode parasite of swines. The aim of this study was to observe Pochonia chlamydosporia fungus on biological control of A. suum eggs after fungus passage through swines gastrointestinal tract. Eighteen pigs, previously dewormed, were randomly divided into three groups: group 1, treated with the fungus isolate VC4; group 2, treated with the fungus isolate VC1 and group 3 did not receive fungus (control). In the treated groups, each animal received a 9 g single dose of mycelium mass containing P. chlamydosporia (VC1 or VC4). Thereafter, animal fecal samples were collected at the following intervals: 8, 12, 24, 36, 48, 72 and 96 h after treatment beginning and these were poured in Petri dishes containing 2% water-agar culture medium. Then, 1,000 A. suum eggs were poured into each dish and kept in an incubator at 26 °C and in the dark for 30 days. After this period, approximately 100 eggs were removed from each Petri dish and morphologically analyzed under light microscopy following the ovicidal activity parameters. The higher percentage observed for isolated VC4 eggs destruction was 57.5% (36 h) after fungus administration and for isolate VC1 this percentage was 45.8% (24 h and 72 h) (p > 0.01). P. chlamydosporia remained viable after passing through the gastrointestinal tract of swines, maintaining its ability of destroying A. suum eggs.

[Ivermectin as an adjunct in the treatment of refractory epilepsy].

PubMed

Diazgranados-Sanchez, J A; Mejia-Fernandez, J L; Chan-Guevara, L S; Valencia-Artunduaga, M H; Costa, J L

2017-10-01

Ivermectin, a 22'23 dihydro derivative of avermectins beta-1a, is a highly effective veterinary and human anti parasitic, used to treat endoparasites of difficult control such as filariasis and onchocerciasis, with a median plasma life of at least of 16 hours. The recommended therapeutic doses range from 0.05 to 0.40 mg/kg, without undesirable effects or risk to human life. It went from being a great success in animal health to its application in humans, where it has had great impact. Studies in basic sciences have shown that ivermectin has anticonvulsive effects in different epileptic animal models, where five different mechanisms of action have been described. Descriptive, prospective observational study, performed between 2013 and 2015, with 32 refractory epileptic patients, who received ivermectin as an a dose of adjunctive treatment of 10 mg/day three or seven times a week, controlled every three months, followed by 12-24 months, without withdrawal of anticonvulsant medications that they received previously. Progressively, patients entered into crisis control, at the end of the programmed follow-up period, the total percentage of crisis reduction was 97%, of which 57% did not return to crisis from the beginning of treatment, all patients being free of crisis according to International League Against Epilepsy criteria. Ivermectin has been useful as an adjuvant, achieving a significant decrease in seizures in this group of drug resistant patients.

Mental imagery boosts music compositional creativity.

PubMed

Wong, Sarah Shi Hui; Lim, Stephen Wee Hun

2017-01-01

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

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

PubMed

Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

2015-01-01

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

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

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

Experimental Clostridium perfringens type D enterotoxemia in goats.

PubMed

Uzal, F A; Kelly, W R

1998-03-01

The effects of intraduodenal administration of Clostridium perfringens cultures and culture products in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species. Five conventionally reared, 11-16-week-old Angora goat kids were dosed intraduodenally with whole cultures of C. perfringens type D; five similar animals were dosed with C. perfringens type D filtered culture supernatant; and a third group of five kids was dosed with C. perfringens type D washed cells. Two kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. All five kids inoculated with whole culture and three of five dosed with culture supernatant and with washed cells developed central nervous system signs. Diarrhea was observed in two of five kids inoculated with whole culture, in all five of those dosed with culture supernatant, and in three of five of those that received washed cells. The most striking postmortem findings consisted of lung edema, necrotizing pseudomembranous colitis, and cerebral vasogenic edema. The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease.

Alterations of selected iron management parameters and activity in food-restricted female Wistar rats (animal anorexia models).

PubMed

Wojciak, Rafal W

2014-03-01

The aim of this study was to assess the influence of food-restricted diets (anorexia models) on iron management and activity of rats. 48 rats were divided into 6 groups: 1 control (K) and 5 testing groups (K/2, GI, GII, GIII, GIV). K was fed ad libitum. K/2 received half the portion of the diet of K. The other groups received 100% of the diet eaten by K, but with different models of food restriction: GI-1 day on, 1 day starvation; GII-2 days on, 2 days starvation; GIII-3 days on, 3 days starvation; and GIV-4 days on, 4 days starvation. As a result, all testing groups ate half of the diet consumed by the control group. The concentrations of iron in selected tissues, ferritin, and selected iron management parameters in blood were examined, as well as the animals' activities associated with food craving. The animal anorexia models used in this study had a significant influence on the blood concentrations of hemoglobin (p < 0.01), hematocrit (p < 0.05), RBC (p < 0.05), iron levels in liver (p < 0.05), kidney (p < 0.001), and heart (p < 0.05), the serum ferritin concentration (p < 0.001) and the rats activity (p < 0.001); whereas there was no influence on the other parameters. Generally, the statistically negative effects of starvation models on iron management parameters and activity of animals were observed. However, these effects were dependent on the model of anorexia more than on the quantity of food intake. The negative effect of food deprivation on iron deficiency and rat activities were observed in all groups; however, the strongest effect was noticed in those animals subject to chronic starvation. Acute deprivations caused the reduction of activity in the rats, however, chronic starvation caused an increase in the activity of the first phase of the experiment, followed by a decline in the subsequent phase. It is possible that stress and frustration as well as depression may be caused by insufficient food intake, and as a result, by iron deficiency in a diet similar to human anorexia. However, more animal/human comparison studies are necessary.

Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

PubMed

Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

2013-09-01

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice.

PubMed

Caforio, Alida L P; Angelini, Annalisa; Blank, Miri; Shani, Alice; Kivity, Shaye; Goddard, Gisele; Doria, Andrea; Schiavo, Alessandro; Testolina, Martina; Bottaro, Stefania; Marcolongo, Renzo; Thiene, Gaetano; Iliceto, Sabino; Shoenfeld, Yehuda

2015-01-20

Human autoimmune myocarditis is characterized by an increased frequency of serum organ and disease-specific anti-heart autoantibodies (AHA) in affected patients. To assess whether AHA are directly pathogenic, we used the passive transfer technique of AHA from patients to normal Balb/c mice to induce an experimental myocarditis. In keeping with a classical passive transfer experiment, sera from 5 AHA positive myocarditis patients (3 male, mean age 30 ± 11 years, 3 with giant cell and 2 with lymphocytic myocarditis) were affinity purified and injected into 25 Balb/c mice. As controls, affinity purified sera from 5 healthy donors were passively transferred to 25 Balb/c mice. Further 15 control mice were injected with phosphate-buffered saline and 9 mice did not receive any injection. In all patients cardiac-specific AHA of IgG class had been previously detected by an indirect immunofluorescence (IFL) technique on cryostat sections of O blood group human heart. The animals were sacrificed after 4 weeks and the hearts were blindly examined for histological evidence of myocarditis by an expert cardiac pathologist. Myocarditis was present in 13/25 (52%) of the mice which received affinity-purified IgG from patients. The findings of severe, moderate or mild myocarditis were more common in the mice which received affinity-purified IgG from patients (20%; 20% and 12%) than in control animals (2%, p=0.01; 0%, p=0.003; and 0%, p=0.04 respectively). These findings provide a new evidence for AHA-mediated pathogenicity in human myocarditis, according to Rose-Witebsky criteria. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

PubMed

Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

2018-03-14

l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p < 0.0001) and shortened seizure duration ( p = 0.028). In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p < 0.0001) and reduced the activity of catalase enzyme ( p = 0.0006) and increased antioxidant GSH activity ( p < 0.0001). Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p < 0.0001) and β-catenin ( p < 0.0001). Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

Creatine supplementation and oxidative stress in rat liver

PubMed Central

2013-01-01

Background The objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats. Methods Forty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training equivalent to the maximal lactate steady state phase; and supplemented-trained (TCr) rats were given a balanced diet supplemented with 2% creatine and subjected to intense exercise training equivalent to the maximal lactate steady state phase. At the end of the experimental period, concentrations of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS) were measured as well as the enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were also determined. Results Hepatic creatine levels were highest in the CCr and TCr groups with increased concentration of H2O2 observed in the T and TCr animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was increased in the T and TCr groups while CAT was elevated in the CCr and TCr groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal subsets. Conclusions Our results demonstrate that creatine supplementation acts in an additive manner to physical training to raise antioxidant enzymes in rat liver. However, because markers of liver oxidative stress were unchanged, this finding may also indicate that training-induced oxidative stress cannot be ameliorated by creatine supplementation. PMID:24325803

The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats.

PubMed

Peng, Mian; Wang, Yan-Lin; Wang, Fei-Fei; Chen, Chang; Wang, Cheng-Yao

2012-11-01

Neuroinflammatory response triggered by surgery has been increasingly reported to be associated with postoperative cognitive dysfunction. Proinflammatory cytokines, such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), play a pivotal role in mediating surgery-induced neuroinflammation. The role of cyclooxygenase-2 (COX-2), a critical regulator in inflammatory response, in surgery-induced neuroinflammation is still unknown. The aim of the study was to investigate the changes of COX-2 expression and prostaglandin E2 (PGE2) production in the hippocampus in aged rats following partial hepatectomy. The effects of selective COX-2 inhibitor (parecoxib) on hippocampal proinflammatory cytokine expression were also evaluated. Aged rats were randomly divided into three groups: control (n = 10), surgery (n = 30), and parecoxib (n = 30). Control animals received sterile saline to control for the effects of injection stress. Rats in the surgery group received partial hepatectomy under isoflurane anesthesia and sterile saline injection. Rats in the parecoxib group received surgery and anesthesia similar to surgery group rats, and parecoxib treatment. On postanesthetic days 1, 3, and 7, animals were euthanized to assess levels of hippocampal COX-2 expression, PGE2 production, and cytokines IL-1β and TNF-α expression. The effects of parecoxib on proinflammatory cytokine expression were also assessed. Partial hepatectomy significantly increased COX-2 expression, PGE2 production, and proinflammatory cytokine expression in the hippocampus in aged rats on postoperative days 1 and 3. Parecoxib inhibited hippocampal IL-1β and TNF-α expression through downregulation of the COX-2/PGE2 pathway. COX-2 may play a critical role in surgery-induced neuroinflammation. The COX-2 inhibitor may be a promising candidate for treatment of neuroinflammation caused by surgical trauma. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

PubMed

Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

2014-06-01

Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Antibody-enhanced dengue disease generates a marked CNS inflammatory response in the black-tufted marmoset Callithrix penicillata.

PubMed

Vasconcelos, Barbara Cristina Baldez; Vieira, Juliana Almeida; Silva, Geane Oliveira; Fernandes, Taiany Nogueira; Rocha, Luciano Chaves; Viana, André Pereira; Serique, Cássio Diego Sá; Filho, Carlos Santos; Bringel, Raissa Aires Ribeiro; Teixeira, Francisco Fernando Dacier Lobato; Ferreira, Milene Silveira; Casseb, Samir Mansour Moraes; Carvalho, Valéria Lima; de Melo, Karla Fabiane Lopes; de Castro, Paulo Henrique Gomes; Araújo, Sanderson Corrêa; Diniz, José Antonio Picanço; Demachki, Samia; Anaissi, Ana Karyssa Mendes; Sosthenes, Marcia Consentino Kronka; Vasconcelos, Pedro Fernando da Costa; Anthony, Daniel Clive; Diniz, Cristovam Wanderley Picanço; Diniz, Daniel Guerreiro

2016-02-01

Severe dengue disease is often associated with long-term neurological impairments, but it is unclear what mechanisms are associated with neurological sequelae. Previously, we demonstrated antibody-enhanced dengue disease (ADE) dengue in an immunocompetent mouse model with a dengue virus 2 (DENV2) antibody injection followed by DENV3 virus infection. Here we migrated this ADE model to Callithrix penicillata. To mimic human multiple infections of endemic zones where abundant vectors and multiple serotypes co-exist, three animals received weekly subcutaneous injections of DENV3 (genotype III)-infected supernatant of C6/36 cell cultures, followed 24 h later by anti-DENV2 antibody for 12 weeks. There were six control animals, two of which received weekly anti-DENV2 antibodies, and four further animals received no injections. After multiple infections, brain, liver, and spleen samples were collected and tissue was immunolabeled for DENV3 antigens, ionized calcium binding adapter molecule 1, Ki-67, TNFα. There were marked morphological changes in the microglial population of ADE monkeys characterized by more highly ramified microglial processes, higher numbers of trees and larger surface areas. These changes were associated with intense TNFα-positive immunolabeling. It is unclear why ADE should generate such microglial activation given that IgG does not cross the blood-brain barrier, but this study reveals that in ADE dengue therapy targeting the CNS host response is likely to be important. © 2015 Japanese Society of Neuropathology.

Polymyxin B moderates acidosis and hypotension in established, experimental gram-negative septicemia.

PubMed

Flynn, P M; Shenep, J L; Stokes, D C; Fairclough, D; Hildner, W K

1987-11-01

Polymyxin B (PMB), an antibiotic, and sodium deoxycholate (NaD), a bile salt, are surface-active agents. Each protected mice against an otherwise lethal challenge with purified endotoxin (P less than .001). To determine if either of these agents was effective in treating established, overwhelming gram-negative septicemia, we infected rabbits by intraperitoneal injection of Escherichia coli K1. Animals were treated with moxalactam 1 hr after infection, then randomly assigned to groups receiving either saline, PMB, or NaD. Serial samples of blood were assayed for bacterial concentration, levels of plasma endotoxin, arterial blood gases, and complete blood cell counts. Physiologic functions were monitored continuously. Although levels of bacteremia and endotoxemia were similar in all three groups, rabbits receiving PMB had significantly higher mean arterial blood pressure, blood pH, and bicarbonate concentrations than did control rabbits (P less than .05). Rabbits receiving NaD fared no better than controls. In this model, PMB moderates some of the deleterious effects of established, overwhelming gram-negative bacterial sepsis.

Histopathological and immunohistochemical changes in the testes of rabbits after injection with the growth promoter boldenone.

PubMed

Tousson, Ehab; El-Moghazy, Mostafa; Massoud, Ahmed; Akel, Amani

2012-03-01

Recently, boldenone (androgenic steroid) is used in improvement of the growth and food conversion in food-producing animals. In addition, it is used by bodybuilders during both off-season and precontest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the possible effect of growth promoter boldenone undecylenate on the structure and functions of rabbit testes. A total of 32 adult New Zealand rabbits were divided into 4 groups. The first group in the control group includes animals that were intramuscularly injected with olive oil and dissected after 3 weeks. Three experimental groups include animals that receive 1, 2, and 3 intramuscular injections of 5 mg/kg body weight boldenone, and dissected after 3, 6, and 9 weeks, respectively. Treating rabbits with boldenone increased the testosterone levels compared to the control group. Seminiferous tubules of the rabbit testis treated with boldenone showed reduced development and degeneration of the germinal epithelium, leading to debris and syncytial cell formation in the lumina of seminiferous tubules. Our immunohistochemical results indicated severe reduction in proliferating cell nuclear antigen-positive spermatogonia in boldenone-treated animals as compared to the control group. These findings explain the common phenomena among athletics and bodybuilders who suffer from infertility as they were injected with some drugs such as steroids (boldenone) to build muscles.

Dietary cation and anion difference: Effects on milk production and body fluid distribution in lactating dairy goats under tropical conditions.

PubMed

Nguyen, Thiet; Chaiyabutr, Narongsak; Chanpongsang, Somchai; Thammacharoen, Sumpun

2018-01-01

This study aimed to determine the effect of dietary cation and anion difference (DCAD) on milk production and body fluid distribution in lactating dairy goats. Ten dairy goats were selected and divided into two groups, five animals each. Animals received either control DCAD (control, 22.81 mEq/100 g dry matter (DM)) or high DCAD (DCAD, 39.08 mEq/100 g DM). The results indicated that rectal temperature (Tr), respiration rate, milk yield and compositions did not differ between groups. But the percentage change of Tr from the DCAD group was lower than the control group between 09.00 and 13.00 hours. DM intake tended to increase in the DCAD group. Dairy goats in the DCAD group drank more water, but urinary excretion and plasma antidiuretic hormone concentration remained unchanged. Apparent water balance was higher from the DCAD group over 24 h. There was no effect of DCAD on plasma and blood volumes, but tended to increase in extracellular fluid and thereby increased total body water. The present results indicate that animals supplemented with high DCAD increase their total body water and apparent water balance. These results have contributed to the process of adaptation for evaporative cooling and would be useful in slowing down the elevation in Tr. © 2017 Japanese Society of Animal Science.

Cortical plasticity and preserved function in early blindness

PubMed Central

Renier, Laurent; De Volder, Anne G.; Rauschecker, Josef P.

2013-01-01

The “neural Darwinism” theory predicts that when one sensory modality is lacking, as in congenital blindness, the target structures are taken over by the afferent inputs from other senses that will promote and control their functional maturation (Edelman, 1993). This view receives support from both cross-modal plasticity experiments in animal models and functional imaging studies in man, which are presented here. PMID:23453908

Retinoprotective effect of Epithalon in campbell rats of various ages.

PubMed

Khavinson, V Kh; Razumovsky, M I; Trofimova, S V; Razumovskaya, A M

2003-05-01

We studied the retinoprotective effect of Epithalon administered to the offspring of Campbell rats during postnatal ontogeny and to mothers before mating and during pregnancy. After this treatment the morphological structure and functional activity of the retina were preserved for a longer period compared to control rats (by 2 times) and to the animals receiving the peptide only during postnatal ontogeny (by 30%).

Duration of an induced resistance of sheep to acute poisoning by Crotalaria retusa seeds

USDA-ARS?s Scientific Manuscript database

The aim of this study was to determine the duration of the resistance after the end of the ingestion of non-toxic doses of Crotalaria retusa seeds. Ten sheep were divided into 3 groups of 3 animals each and a control group with 1 sheep. To induce resistance, sheep in groups 1, 2, and 3 received 20 d...

9 CFR 121.15 - Training.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Training. 121.15 Section 121.15 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES...., laboratories, growth chambers, animal rooms, greenhouses, storage areas, shipping/receiving areas, production...

Effects of animal-assisted therapy on concentration and attention span in patients with acquired brain injury: A randomized controlled trial.

PubMed

Gocheva, Vanya; Hund-Georgiadis, Margret; Hediger, Karin

2018-01-01

Previous studies have reported that brain-injured patients frequently suffer from cognitive impairments such as attention and concentration deficits. Numerous rehabilitation clinics offer animal-assisted therapy (AAT) to address these difficulties. The authors' aim was to investigate the immediate effects of AAT on the concentration and attention span of brain-injured patients. Nineteen patients with acquired brain injury were included in a randomized, controlled, within-subject trial. The patients alternately received 12 standard therapy sessions (speech therapy, physiotherapy, occupational therapy) and 12 paralleled AAT sessions with comparable content. A total of 429 therapy sessions was analyzed consisting of 214 AAT and 215 control sessions. Attention span and instances of distraction were assessed via video coding in Noldus Observer. The Mehrdimensionaler Befindlichkeitsbogen ([Multidimensional Affect Rating Scale] MDBF questionnaire; Steyer, Schwenkmezger, Notz, & Eid, 1997) was used to measure the patient's self-rated alertness. Concentration was assessed through Visual Analogue Scale (VAS) via self-assessment and therapist's ratings. The patients' attention span did not differ whether an animal was present or not. However, patients displayed more instances of distraction during AAT. Moreover, patients rated themselves more concentrated and alert during AAT sessions. Further, therapists' evaluation of patients' concentration indicated that patients were more concentrated in AAT compared with the control condition. Although the patients displayed more instances of distraction while in the presence of an animal, it did not have a negative impact on their attention span. In addition, patients reported to be more alert and concentrated when an animal was present. Future studies should examine other attentional processes such as divided attention and include neurobiological correlates of attention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Acetylcholine release in the mesocorticolimbic dopamine system during cocaine seeking: conditioned and unconditioned contributions to reward and motivation.

PubMed

You, Zhi-Bing; Wang, Bin; Zitzman, Dawnya; Wise, Roy A

2008-09-03

Microdialysis was used to assess the contribution to cocaine seeking of cholinergic input to the mesocorticolimbic dopamine system in ventral tegmental area (VTA). VTA acetylcholine (ACh) was elevated in animals lever pressing for intravenous cocaine and in cocaine-experienced and cocaine-naive animals passively receiving similar "yoked" injections. In cocaine-trained animals, the elevations comprised an initial (first hour) peak to approximately 160% of baseline and a subsequent plateau of 140% of baseline for the rest of the cocaine intake period. In cocaine-naive animals, yoked cocaine injections raised ACh levels to the 140% plateau but did not cause the initial 160% peak. In cocaine-trained animals that received unexpected saline (extinction conditions) rather than the expected cocaine, the initial peak was seen but the subsequent plateau was absent. VTA ACh levels played a causal role and were not just a correlate of cocaine seeking. Blocking muscarinic input to the VTA increased cocaine intake; the increase in intake offset the decrease in cholinergic input, resulting in the same VTA dopamine levels as were seen in the absence of the ACh antagonists. Increased VTA ACh levels (resulting from 10 microM VTA neostigmine infusion) increased VTA dopamine levels and reinstated cocaine seeking in cocaine-trained animals that had undergone extinction; these effects were strongly attenuated by local infusion of a muscarinic antagonist and weakly attenuated by a nicotinic antagonist. These findings identify two cholinergic responses to cocaine self-administration, an unconditioned response to cocaine itself and a conditioned response triggered by cocaine-predictive cues, and confirm that these cholinergic responses contribute to the control of cocaine seeking.

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

PubMed

Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

2001-11-01

To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.

Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep

PubMed Central

SNYDER, Candice C.; WOLFE, Katherine B.; GISSLEN, Tate; KNOX, Christine L.; KEMP, Matthew W.; KRAMER, Boris W.; NEWNHAM, John P.; JOBE, Alan H.; KALLAPUR, Suhas G.

2013-01-01

Objective Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E. coli lipopolysaccharide (LPS). Methods Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U. parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion Acute U. parvum exposure (7d) can suppress LPS induced chorioamnionitis. PMID:23410690

Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep.

PubMed

Snyder, Candice C; Wolfe, Katherine B; Gisslen, Tate; Knox, Christine L; Kemp, Matthew W; Kramer, Boris W; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

2013-05-01

Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that Ureaplasma colonization of amniotic fluid would modulate chorioamnionitis induced by Escherichia coli lipopolysaccharide (LPS). Sheep received intraamniotic (IA) injections of media (control) or live Ureaplasma either 7 or 70 days before delivery. Another group received IA LPS 2 days before delivery. To test for interactions, U parvum-exposed animals were challenged with IA LPS, and delivered 2 days later. All animals were delivered preterm at 125 ± 1 day of gestation. Both IA Ureaplasma and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of proinflammatory cytokines and myeloperoxidase in leukocytes, while Ureaplasma alone caused modest responses. Interestingly, 7-day but not 70-day Ureaplasma exposure significantly down-regulated LPS-induced proinflammatory cytokines and myeloperoxidase expression in the chorioamnion. Acute (7-day) U parvum exposure can suppress LPS-induced chorioamnionitis. Copyright © 2013 Mosby, Inc. All rights reserved.

Phytochemical screening and acute toxicity evaluation of Telfairia occidentalis aqueous extracts on rats.

PubMed

Anthony, Ogbonnaya Enyinnaya; Ojeifo, Uadia Patrick

2016-05-01

The phytochemical composition and acute toxicity of Telfairia occidentalis aqueous extracts were investigated in this study. Phytochemical screening was carried out on the pulverized leaf, root, pod and stem samples. Proximate analysis was also conducted for the root to ascertain the effect of drying procedures on its composition. Fifty-six (56) Wister albino rats, male and female were divided into two broad groups of 28 animals per group. The first group was randomly separated into seven (7) groups of four (4) animals per group. The control group received distilled water alone while the other groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of the Soluble and Insoluble Tefairia occidentalis root fraction. The second group of 28 animals was also distributed into 7 groups of 4 animals per group. Six test groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of Telfairia occidentalis fruit and stem extracts. The animals were observed for the first 12hr for any toxic symptoms and for 48 hr for mortality rate. Surviving animals were sacrificed after 48 hours. Phytochemical screening results reveal the presence of tannins, flavonoid, steroid, terpenoids, saponin, alkaloid, glycosides, proteins and carbohydrates. Flavonoid and saponin was not detected in stem sample; alkaloid is present in all samples except pod; and cyanogenic glycoside was found in both root and pod samples. Except for the fibre content, the method of preparation of the root had no significant effect on the proximate composition of the sample. The root extracts cause insignificant reduction in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) activities, except for the significant reduction in ALT activity at highest dose. The pod extract significantly increased the ALT and AST activities, which is dose dependent, while the stem extract only caused increased activity of ALT, but not AST. None of the extracts administered had any significant effect on the levels of serum creatinine and urea. Thus, while the root extract may exhibit some hepatoprotective effect (or nephrotoxic due to cyanogenic glycoside) and its proximate composition, not affected by heat treatment, the pod and stem extracts of Telfairia occidentalis may have some effects on rat hepatocytes.

Effects of encapsulated nitrate on growth performance, carcass characteristics, nitrate residues in tissues, and enteric methane emissions in beef steers: Finishing phase.

PubMed

Lee, C; Araujo, R C; Koenig, K M; Beauchemin, K A

2017-08-01

A finishing feedlot study was conducted with beef steers to determine effects of encapsulated nitrate (EN) on growth performance, carcass characteristics, methane production, and nitrate (NO) residues in tissues. The 132 crossbred steers were backgrounded in a feedlot for 91 d and transitioned for 28 days to the high-concentrate diets evaluated in the present study, maintaining the treatment and pen assignments designated at the start of the backgrounding period. The steers were initially assigned to 22 pens (6 animals per pen) in a randomized complete block design with BW (18 pens) and animals designated for methane measurement (4 pens) as blocking factors. Five animals in each pen designated for methane measurement (total of 20 animals) were monitored for methane emissions in respiratory chambers twice during the experiment. Pens received 3 dietary treatments (7 pens each): Control, a finishing diet supplemented with urea; 1.25% EN, control diet supplemented with 1.25% encapsulated NO in dietary DM that partially replaced urea; and 2.5% EN, control diet supplemented with 2.5% EN (DM basis) fully replacing urea. The final pen designated only for methane measurement received a fourth dietary treatment, 2.3% UEN, the control diet supplemented with unencapsulated NO (UEN) fully replacing urea. The cattle weighed 449 ± SD 32 kg at the start of the 150-d finishing period. The 2.5% EN diet decreased ( < 0.01) DMI compared with Control and 1.25% EN diets. Feeding EN tended to increase ( = 0.092) ADG compared with Control, and G:F was improved ( < 0.01) for EN compared with Control. No differences in methane production (g/d) and yield (g/kg DMI) were observed among treatments. Inclusion of EN in the diets increased ( ≤ 0.03) sorting in favor of large and medium particles and against small and fine particles. Plasma NO and NO concentrations were elevated ( < 0.01) with EN in a dose-response manner, but total blood methemoglobin levels for all treatments were low, below the detection limit. Feeding EN increased ( < 0.01) NO concentrations of samples from muscle, fat, liver, and kidney; NO concentrations of these tissues were similar between 1.25% EN and 2.3% UEN. In conclusion, inclusion of 2.5% EN in a finishing diet (DM basis; about 2% NO) did not cause NO toxicity or any health problems in the long term. In comparison with supplemental urea, feeding EN improved feed efficiency despite increases in sorting against dietary EN.

Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression✩,✩✩

PubMed Central

Joshi, R.N.; Safadi, F.F.; Barbe, M.F.; Carpio-Cano, Fe Del; Popoff, S.N.; Yingling, V.R.

2013-01-01

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals’ intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression. PMID:21807131

A Model of Post-Traumatic Epilepsy After Penetrating Brain Injuries: Effect of Lesion Size and Metal Fragments

PubMed Central

Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.

2014-01-01

Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332

In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor.

PubMed

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

2012-12-01

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

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.

PubMed

Araújo, Wedson F; Naves, Marcelo A; Ravanini, Juliana N; Schor, Nestor; Teixeira, Vicente P C

2015-09-01

Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model. Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34. Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls. Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model. Copyright © 2015 Elsevier Inc. All rights reserved.

Protection induced by a glycoprotein E-deleted bovine herpesvirus type 1 marker strain used either as an inactivated or live attenuated vaccine in cattle.

PubMed

Romera, Sonia Alejandra; Puntel, Mariana; Quattrocchi, Valeria; Del Médico Zajac, Paula; Zamorano, Patricia; Blanco Viera, Javier; Carrillo, Consuelo; Chowdhury, Shafiqul; Borca, Manuel V; Sadir, Ana M

2014-01-08

Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections; causing a high economic loss in all continents. Use of marker vaccines in IBR eradication programs is widely accepted since it allows for protection of the animals against the disease while adding the possibility of differentiating vaccinated from infected animals.The aim of the present study was the development and evaluation of safety and efficacy of a glycoprotein E-deleted (gE-) BoHV-1 marker vaccine strain (BoHV-1ΔgEβgal) generated by homologous recombination, replacing the viral gE gene with the β-galactosidase (βgal) gene. In vitro growth kinetics of the BoHV-1ΔgEβgal virus was similar to BoHV-1 LA. The immune response triggered by the new recombinant strain in cattle was characterized both as live attenuated vaccine (LAV) and as an inactivated vaccine. BoHV-1ΔgEβgal was highly immunogenic in both formulations, inducing specific humoral and cellular immune responses. Antibody titers found in animals vaccinated with the inactivated vaccine based on BoHV-1ΔgEβgal was similar to the titers found for the control vaccine (BoHV-1 LA). In the same way, titers of inactivated vaccine groups were significantly higher than any of the LAV immunized groups, independently of the inoculation route (p < 0.001). Levels of IFN-γ were significantly higher (p < 0.001) in those animals that received the LAV compared to those that received the inactivated vaccine. BoHV-1ΔgEβgal exhibited an evident attenuation when administered as a LAV; no virus was detected in nasal secretions of vaccinated or sentinel animals during the post-vaccination period. BoHV-1ΔgEβgal, when used in either formulation, elicited an efficient immune response that protected animals against challenge with virulent wild-type BoHV-1. Also, the deletion of the gE gene served as an immunological marker to differentiate vaccinated animals from infected animals. All animals vaccinated with the BoHV-1ΔgE βgal strain were protected against disease after challenge and shed significantly less virus than control calves, regardless of the route and formulation they were inoculated. Based on its attenuation, immunogenicity and protective effect after challenge, BoHV-1ΔgEβgal virus is an efficient and safe vaccine candidate when used either as inactivated or as live attenuated forms.

Animal source foods have a positive impact on the primary school test scores of Kenyan schoolchildren in a cluster-randomised, controlled feeding intervention trial.

PubMed

Hulett, Judie L; Weiss, Robert E; Bwibo, Nimrod O; Galal, Osman M; Drorbaugh, Natalie; Neumann, Charlotte G

2014-03-14

Micronutrient deficiencies and suboptimal energy intake are widespread in rural Kenya, with detrimental effects on child growth and development. Sporadic school feeding programmes rarely include animal source foods (ASF). In the present study, a cluster-randomised feeding trial was undertaken to determine the impact of snacks containing ASF on district-wide, end-term standardised school test scores and nutrient intake. A total of twelve primary schools were randomly assigned to one of three isoenergetic feeding groups (a local plant-based stew (githeri) with meat, githeri plus whole milk or githeri with added oil) or a control group receiving no intervention feeding. After the initial term that served as baseline, children were fed at school for five consecutive terms over two school years from 1999 to 2001. Longitudinal analysis was used controlling for average energy intake, school attendance, and baseline socio-economic status, age, sex and maternal literacy. Children in the Meat group showed significantly greater improvements in test scores than those in all the other groups, and the Milk group showed significantly greater improvements in test scores than the Plain Githeri (githeri+oil) and Control groups. Compared with the Control group, the Meat group showed significant improvements in test scores in Arithmetic, English, Kiembu, Kiswahili and Geography. The Milk group showed significant improvements compared with the Control group in test scores in English, Kiswahili, Geography and Science. Folate, Fe, available Fe, energy per body weight, vitamin B₁₂, Zn and riboflavin intake were significant contributors to the change in test scores. The greater improvements in test scores of children receiving ASF indicate improved academic performance, which can result in greater academic achievement.

Effect of Preservation Methods of Oil Palm Sap (Elaeis guineensis) on the Reproductive Indices of Male Wistar Rats

PubMed Central

Ikegwu, Theophilus Maduabuchukwu; Ochiogu, Izuchukwu Shedrack

2014-01-01

Abstract Thirty male Wistar rats, split into five groups of six rats each, were administered different forms of oil palm tree (Elaeis guineensis) sap samples by gavage based on 1.5% of their weekly body weights. Group 1 which served as control received only water, group 2 received pasteurized palm sap (PPS), group 3 received market palm wine (MPW), group 4 received frozen palm sap (FPS), whereas group 5 received fresh palm sap (FrPS). Chemical composition of the sap samples was determined. Normal feed and water were fed ad libitum. After 2 months of treatment, each male rat group was allowed 7 days to mate with six female Wistar rats. Thereafter, blood and epididymal samples were collected for testosterone assay and sperm count, respectively, before they were humanely sacrificed and testicular tissues taken for testicular histology. Litter weight and size of the pups produced by the females of each group were determined at birth. The sap samples contained carbohydrate (0.01–11.71%), protein (1.56–1.95%), ash (0.22–0.35%), moisture (92.55–98.24%), and alcohol (0.26–3.50%). PPS-treated rat group had significantly (P<.05) decreased sperm count (42.60±23.64×106), abnormal increase in testosterone level, and necrosis in the histology of the testes with reduced spermatogenetic activity, compared with other treatment groups. The female rats crossed with male rats fed on FrPS or FPS produced the highest number of pups followed by the control group. This study demonstrated that the intake of FrPS improved fertility in male animals, but its administration for a long period led to necrotic changes in the testes, whereas pasteurization of palm sap, impacted negatively on the reproductive indices of male animals. PMID:25101691

Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

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

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Pastor, Angel M

2013-01-01

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants.

TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding

PubMed Central

Naylor, Amy J.; Desanti, Guillaume; Saghir, Atif N.

2017-01-01

Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNFΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy ‘infliximab’ might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNFΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P < 0.05), while measures of pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the breeding groups, TNFΔARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69 ± 0.22 versus infliximab 3.00 ± 0.19; P < 0.005). Furthermore, prior to infliximab, TNFΔARE males had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This study is the first to report that regular administration of infliximab is effective at suppressing disease activity and improving animal welfare in TNFΔARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNFΔARE males. PMID:28480797

TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding.

PubMed

Naylor, Amy J; Desanti, Guillaume; Saghir, Atif N; Hardy, Rowan S

2018-02-01

Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNF ΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy 'infliximab' might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNF ΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNF ΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNF ΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P < 0.05), while measures of pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the breeding groups, TNF ΔARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69 ± 0.22 versus infliximab 3.00 ± 0.19; P < 0.005). Furthermore, prior to infliximab, TNF ΔARE males had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This study is the first to report that regular administration of infliximab is effective at suppressing disease activity and improving animal welfare in TNF ΔARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNF ΔARE males.

Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats.

PubMed

Jastreboff, P J; Zhou, S; Jastreboff, M M; Kwapisz, U; Gryczynska, U

1997-01-01

The effects of an extract from Ginkgo biloba, EGb 761, on tinnitus were tested using an animal model of tinnitus. Daily oral administration of EGb 761 in doses from 10 to 100 mg/ kg/day began 2 weeks before behavioral procedures and continued until the end of the experiment. Tinnitus was induced by daily administration of 321 mg/kg sodium salicylate s.c. (corresponding to 275 mg/kg/day of salicylate acid) in fourteen groups of pigmented rats, 6 animals/group. The results from salicylate- and EGb-761-treated animals were compared to control groups receiving either salicylate, saline, or EGb 761 only in doses of 100 mg/kg. Administration of EGb 761 resulted in a statistically significant decrease of the behavioral manifestation of tinnitus for doses of 25, 50 and 100 mg/kg/ day.

Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cysts in rats.

PubMed

Poretsky, L; Clemons, J; Bogovich, K

1992-08-01

Tonically elevated serum luteinizing hormone (LH) and hyperinsulinemia are prominent features of polycystic ovary syndrome (PCO) in women, but the relative roles of LH and insulin in the pathogenesis of PCO is still unknown. The present study was undertaken to determine the effect(s) hyperinsulinemia might have on the induction of follicular cysts by LH/human chorionic gonadotropin (hCG) in the rat. Beginning on day 85 of age, adult female rats were given one of the following in vivo treatments: (1) vehicle alone; (2) a high-fat diet to control for the effects of weight-gain; (3) up to 6 U insulin per day; (4) 50 micrograms gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) per day; (5) 1.5 IU hCG twice daily; (6) insulin + hCG; (7) insulin + GnRHant; (8) hCG + GnRHant; or (9) hCG + insulin + GnRHant. After 22 days of treatment, animals were killed on day 23, trunk blood was collected, and ovaries were excised for histological study. Regular cycles, assessed by vaginal smears, ceased after 10 days for most animals in treatment groups receiving hCG, but continued in all other treatment groups. All the animals in each hCG-treated group developed either unilateral or bilateral cystic ovaries, while no animals in the groups not receiving hCG developed follicular cysts. More animals from each group treated with both hCG and insulin possessed bilateral ovarian cysts than did rats treated with hCG alone: 80% and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder.

PubMed

Zeeb, Fiona D; Li, Zhaoxia; Fisher, Daniel C; Zack, Martin H; Fletcher, Paul J

2017-11-01

An animal model of gambling disorder, previously known as pathological gambling, could advance our understanding of the disorder and help with treatment development. We hypothesized that repeated exposure to uncertainty during gambling induces behavioural and dopamine (DA) sensitization - similar to chronic exposure to drugs of abuse. Uncertainty exposure (UE) may also increase risky decision-making in an animal model of gambling disorder. Male Sprague Dawley rats received 56 UE sessions, during which animals responded for saccharin according to an unpredictable, variable ratio schedule of reinforcement (VR group). Control animals responded on a predictable, fixed ratio schedule (FR group). Rats yoked to receive unpredictable reward were also included (Y group). Animals were then tested on the Rat Gambling Task (rGT), an analogue of the Iowa Gambling Task, to measure decision-making. Compared with the FR group, the VR and Y groups experienced a greater locomotor response following administration of amphetamine. On the rGT, the FR and Y groups preferred the advantageous options over the risky, disadvantageous options throughout testing (40 sessions). However, rats in the VR group did not have a significant preference for the advantageous options during sessions 20-40. Amphetamine had a small, but significant, effect on decision-making only in the VR group. After rGT testing, only the VR group showed greater hyperactivity following administration of amphetamine compared with the FR group. Reward uncertainty was the only gambling feature modelled. Actively responding for uncertain reward likely sensitized the DA system and impaired the ability to make optimal decisions, modelling some aspects of gambling disorder.

The role of virus dose in experimental bovine leukemia virus infection in sheep.

PubMed

Stirtzinger, T; Valli, V E; Miller, J M

1988-04-01

Twenty-four, six month old lambs were assembled into four groups of five animals each and one group of four animals. All groups were inoculated with lymphocytes from a single donor lamb infected with bovine leukemia virus. The inoculum varied from 250 to 250,000 lymphocytes, in tenfold increments. Animals were exposed by intradermal injection in the neck region immediately anterior to the left shoulder joint. All groups were monitored at 0, 3, 7 and 12 weeks after inoculation using the following procedures: a. Syncytia induction assay for detection of bovine leukemia virus in peripheral blood lymphocytes. b. Agar gel immunodiffusion against the gp51 antigen of bovine leukemia virus for the detection of antibovine leukemia virus gp51 antibody. c. Lymphocyte stimulation test for the assessment of cell-mediated immunity using mitogen, nonfractionated bovine leukemia virus antigen, and partially purified bovine lymphoma tumor-associated antigen for the in vitro activation of lymphocytes from bovine leukemia virus-inoculated and sham-inoculated, control animals. d. Routine hematological techniques for the assessment of total leukocyte and lymphocyte counts. The median infectious dose for lymphocytes from the single bovine leukemia virus-infected donor used in this study was determined to be 2000 cells. The syncytia induction assay detected more infected individuals (13/23) at an earlier time than did the agar gel immunodiffusion assay (10/23). Using either serological or virus isolation techniques, infected animals were first detected at three weeks postinoculation in the group receiving the high-dose inoculum and at seven weeks postinoculation in groups receiving low- or medium-dose inocula.(ABSTRACT TRUNCATED AT 250 WORDS)

Glutamine prevents oxidative stress in a model of portal hypertension.

PubMed

Zabot, Gilmara Pandolfo; Carvalhal, Gustavo Franco; Marroni, Norma Possa; Licks, Francielli; Hartmann, Renata Minuzzo; da Silva, Vinícius Duval; Fillmann, Henrique Sarubbi

2017-07-07

To evaluate the protective effects of glutamine in a model of portal hypertension (PH) induced by partial portal vein ligation (PPVL). Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum . Twenty-four male Wistar rats were divided into four experimental groups: (1) control group (SO) - rats underwent exploratory laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to laparotomy and were treated intraperitoneally with glutamine; (3) portal hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) after PPVL. Lipid peroxidation of the membrane was increased in the animals subjected to PH ( P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups ( P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH ( P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH ( P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification (44 pixel = 1 μm) were captured. The sum means of all areas, of each group were calculated. The mean areas of eNOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for eNOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group ( P < 0.01). For iNOS, the control (SO) and control + G (SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of iNOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine ( P < 0.01). Treatment with glutamine prevents gut mucosal injury after PH in rats.

Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice.

PubMed

Osanloo, Naser; Najafi-Abedi, Akram; Jafari, Fatemeh; Javid, Farshid; Pirpiran, Mohsen; Memar Jafari, Mohammad-Reza; Mousavi Khosravi, Seyed Ali; Rahimzadeh Behzadi, Mohammad; Ranjbaran, Mina; Sahraei, Hedayat

2016-07-01

Depression is one of the most frequent psychiatric disorders in the world with occurs with higher incidence in women. In the present study, the effect of water-alcoholic extract of Papaver rhoeas L. on forced swimming test (FST) in Swiss-Webster mice were examined. We used Swiss-Webster mice (20-25 g) to execute FST on them. The plant extract (1, 10, 30, and 100 mg/kg) was injected to the animals 30 minutes before each session. Fluoxetine (20 mg/kg) was used as standard antidepressant drug. In another group of animals, 30 minutes after extract administration, blood samples were taken from retro-orbital sinus for corticosterone assay. Yet in third group, the drugs were injected to the animals and 30 minutes later, their activities were tested in an open field apparatus. Our experiments showed that the extract efficiently reduced FST time both in male and female mice dose-dependently. This effect was comparable with fluoxetine. In addition, corticosterone assay indicated that plasma corticosterone in animals which received extract was higher than those amounts in fluoxetine and saline controls. Moreover, the animals did not show any motor activity deficit in all doses of the extract and fluoxetine compared to saline control. The extract of Papaver rhoeas can reduce immobility time which is comparable to the effect of fluoxetine. Also the effect of the extract is contrary to its effects on plasma corticosterone level and or animals' activity.

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

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

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

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

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats.

PubMed

De Lucca, Romina C; Dutrey, Patricio L; Villarino, Mariano E; Ubios, Angela M

2009-07-01

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5mg/kg and of the second molar in those receiving 6.25mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.

Protein degradation in skeletal muscle during experimental hyperthyroidism in rats and the effect of beta-blocking agents.

PubMed

Angerås, U; Hasselgren, P O

1987-04-01

beta-Blocking agents are increasingly used in the management of hyperthyroid patients. The effect of this treatment on increased muscle protein breakdown in the hyperthyroid state is not known. In the present study, experimental hyperthyroidism was induced in rats by daily ip injections of T3 (100 micrograms/100 g BW) during a 10-day period. Control animals received corresponding volumes of solvent. In groups of rats the selective beta-1-blocking agent metoprolol or the nonselective beta-blocker propranolol was infused by miniosmotic pumps implanted sc on the backs of the animals. Protein degradation was measured in incubated intact soleus and extensor digitorum longus muscles by determining tyrosine release into the incubation medium. The protein degradation rate in incubated extensor digitorum longus and soleus muscles was increased by 50-60% during T3 treatment. Metoprolol or propranolol did not influence muscle protein breakdown in either T3-treated or control animals. The results suggest that T3-induced increased muscle proteolysis is not mediated by beta-receptors, and muscle weakness and wasting in hyperthyroidism might not be affected by beta-blockers.

Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats.

PubMed

Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

2011-09-01

Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (P< 0.05) in diabetic compared with controls, and these parameters increased (P< 0.05) in the treated compared with diabetics. Hydroalcoholic extract of U. dioica, before induction of diabetes; has protective role on seminiferous tubules alterations.

Protective Effect of Urtica dioica L. (Urticaceae) on Morphometric and Morphologic Alterations of Seminiferous Tubules in STZ Diabetic Rats

PubMed Central

Golalipour, Mohammad Jafar; Kabiri Balajadeh, Babak; Ghafari, Soraya; Azarhosh, Ramin; Khori, Vahid

2011-01-01

Objective(s) Urtica dioica L. has been known as a medicinal plant in the world. This study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on seminiferous tubules of diabetic rats. Materials and Methods Animals were allocated to control, diabetic and protective groups. Treated animals received extract of U. dioica (100 mg/ kg/ day) IP for the first 5 days and STZ injection on the 6th day. After 5 weeks, testes removed and stained with H&E technique. Results Tubular cell disintegration, sertoli and spermatogonia cell vacuolization, and decrease in sperm concentration observed in diabetic in comparison with control and protective groups. External seminiferous tubular diameter and seminiferous epithelial height significantly reduced (P< 0.05) in diabetic compared with controls, and these parameters increased (P< 0.05) in the treated compared with diabetics. Conclusion Hydroalcoholic extract of U. dioica, before induction of diabetes; has protective role on seminiferous tubules alterations. PMID:23493848

Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing.

PubMed

Lavon, Ophir; Avrahami, Amit; Eisenkraft, Arik

2017-03-14

Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.

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.

Animated pedagogical agents: How the presence and nonverbal communication of a virtual instructor affect perceptions and learning outcomes in a computer-based environment about basic physics concepts

NASA Astrophysics Data System (ADS)

Frechette, M. Casey

One important but under-researched area of instructional technology concerns the effects of animated pedagogical agents (APAs), or lifelike characters designed to enhance learning in computer-based environments. This research sought to broaden what is currently known about APAs' instructional value by investigating the effects of agents' visual presence and nonverbal communication. A theoretical framework based on APA literature published in the past decade guided the design of the study. This framework sets forth that APAs impact learning through their presence and communication. The communication displayed by an APA involves two distinct kinds of nonverbal cues: cognitive (hand and arm gestures) and affective (facial expressions). It was predicted that the presence of an agent would enhance learning and that nonverbal communication would amplify these effects. The research utilized a between-subjects experimental design. Participants were randomly assigned to treatment conditions in a controlled lab setting, and group means were compared with a MANCOVA. Participants received (1) a non-animated agent, (2) an agent with hand and arm gestures, (3) an agent with facial expressions, or (4) a fully animated agent. The agent appeared in a virtual learning environment focused on Kepler's laws of planetary motion. A control group did not receive the visual presence of an agent. Two effects were studied: participants' perceptions and their learning outcomes. Perceptions were measured with an attitudinal survey with five subscales. Learning outcomes were measured with an open-ended recall test, a multiple choice comprehension test, and an open-ended transfer test. Learners presented with an agent with affective nonverbal communication comprehended less than learners exposed to a non-animated agent. No significant differences were observed when a group exposed to a fully animated agent was compared to a group with a non-animated agent. Adding both nonverbal communication channels mitigated the disadvantages of adding just one kind of nonverbal cue. No statistically significant differences were observed on measures of recall or transfer, or on the attitudinal survey. The research supports the notion that invoking a human-like presence in a virtual learning environment prompts strong expectations about the character's realism. When these expectations are not met, learning is hindered.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Evaluation of a postexposure rabies prophylaxis protocol for domestic animals in Texas: 2000-2009.

PubMed

Wilson, Pamela J; Oertli, Ernest H; Hunt, Patrick R; Sidwa, Thomas J

2010-12-15

To determine whether postexposure rabies prophylaxis (PEP) in domestic animals, as mandated in Texas, has continued to be effective and to evaluate preexposure or postexposure vaccination failures from 2000 through 2009. Retrospective case series. 1,014 unvaccinated domestic animals (769 dogs, 126 cats, 72 horses, 39 cattle, 3 sheep, 4 goats, and 1 llama) that received PEP and 12 vaccinated domestic animals (7 dogs and 5 cats) with possible failure of protection. Zoonotic incident reports from 2000 through 2009 were reviewed for information regarding unvaccinated domestic animals that received PEP in accordance with the state protocol after exposure to a laboratory-confirmed rabid animal; reports also were reviewed for any preexposure or postexposure vaccination failures. The state-required PEP protocol was as follows: immediately vaccinate the animal against rabies, isolate the animal for 90 days, and administer booster vaccinations during the third and eighth weeks of the isolation period. From 2000 through 2009, 1,014 animals received PEP; no failures were recorded. One preexposure vaccination failure was recorded. The Texas PEP protocol was used during the 10-year period. Results indicated that an effective PEP protocol for unvaccinated domestic animals exposed to rabies was immediate vaccination against rabies, a strict isolation period of 90 days, and administration of booster vaccinations during the third and eighth weeks of the isolation period.

Influence of novel gallium complexes on the homeostasis of some biochemical and hematological parameters in rats.

PubMed

Gârban, Gabriela; Silaghi-Dumitrescu, Radu; Ioniţă, Hortensia; Gârban, Zeno; Hădărugă, Nicoleta-Gabriela; Ghibu, George-Daniel; Baltă, Cornel; Simiz, Florin-Dan; Mitar, Carmen

2013-12-01

The aim of this study was to detect possible homeostasis changes in some biochemical and hematological parameters after the administration of gallium (Ga) complexes C (24) and C (85) on an experimental animal model (Wistar strain rats). In order to observe chronobiological aspects, a morning (m) and an evening (e) animal series were constituted. Further on, each series were divided into three groups: control (C), experimental I (EI), and experimental II (EII). Both Ga complexes were solubilized in a carrier solution containing polyethylene glycol (PEG) 400, water, and ethanol. Animals of the C groups received the carrier solution by intraperitoneal injection, those from the EI groups received the solubilized C(24) gallium complex, and those of the EII groups received the solubilized C(85) gallium complex. At the end of the experiment, blood and tissue samples were taken and the following parameters were determined: serum concentration of the nonprotein nitrogenous compounds (uric acid, creatinine, and blood urea nitrogen), hematological parameters (erythrocytes, hemoglobin, leukocytes, and platelets), and the kidney tissue concentration of three essential trace elements (Fe, Cu, and Zn). With the exception of uric acid, the results revealed increased concentrations of the nonprotein nitrogenous compounds both in the morning and in the evening experimental groups. Hematological data showed increased levels of erythrocytes, hemoglobin, and leukocytes and decreased platelet levels in the experimental group given the C(24) gallium complex in the morning (EI-m) group; increased levels of leukocytes and decreased levels of the other parameters in the experimental group given the C(24) gallium complex in the evening (EI-e) group; and increased levels of all hematological parameters in the experimental groups receiving the C(85) gallium complex in the morning (EII-m) group and in the evening (EII-e) group. Decreased kidney tissue concentrations of metals were found in all the experimental groups. Fe levels were significantly decreased in the EI-m receiving the C(24) gallium complex and EII-m which received the C(85) gallium complex and in the EII-e group which received the C(85) gallium complex. In the EI-e group which received the C(24) gallium complex, a significant decrease of Cu concentration was reported.

Banana fruit pulp and peel involved in antianxiety and antidepressant effects while invigorate memory performance in male mice: Possible role of potential antioxidants.

PubMed

Samad, Noreen; Muneer, Aqsa; Ullah, Najeeb; Zaman, Aqal; Ayaz, M Mazhar; Ahmad, Ijaz

2017-05-01

The present study was aimed to investigate the anti-stress and memory enhancing effects of banana (Musa sapientum L.) fruit pulp and peel extract in male mice. Locally bred albino Wistar mice were divided into control and 2 test groups (n=10). Control rats received drinking water while test groups were treated with banana fruit pulp (600 mg/kg; oral administration) and extract of banana peel (400mg/kg; oral administration). Behavioral activities of animals were monitored 14 days post administration of banana pulp and peel extract. Depression-like symptoms were measured by forced swimming test (FST). Anxiety like behavior was monitored using light-dark activity (LDA) test and plus maze activity (PMA) test and memory functions of rats were assessed by morris water maze (MWM) test. Following 2 weeks animals were decapitated and brain was removed for estimation of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD) and reduced glutathione (GSH). In the present study both banana peel and pulp increased the time spent in light box and open arm, suggesting anxiolytic effects. A significant decrease in immobility time was observed in FST in both banana pulp and peel treated animals suggesting antidepressant like effects. Moreover, learning and memory assessed by MWM showed decrease in time to reach platform in both short term and long term memory test suggested increased memory function in both banana pulp and peel treated animals as compared to control animals. The activities of all antioxidant enzymes were significantly (p<0.05) greater in banana pulp and peel treated animals than control. It is concluded that both banana pulp and peel have anti-anxiety, antidepressant effect as well as strengthen the memory possibly via its antioxidant mechanism. Therefore, it is recommended that supplementation of banana could be taken a vital role in stress (anxiety and depression) relief and increased in memory function possibly by phyto-antioxidants.

L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

PubMed

Valero, R; García-Valdecasas, J C; Net, M; Beltran, J; Ordi, J; González, F X; López-Boado, M A; Almenara, R; Taurá, P; Elena, M; Capdevila, L; Manyalich, M; Visa, J

2000-09-15

To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

9 CFR 52.2 - Payment of indemnity.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Payment of indemnity. 52.2 Section 52.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... with the amount for net salvage the owner receives when the animals are slaughtered, shall not exceed...

9 CFR 52.2 - Payment of indemnity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Payment of indemnity. 52.2 Section 52.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... with the amount for net salvage the owner receives when the animals are slaughtered, shall not exceed...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2011 CFR

2011-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2013 CFR

2013-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2012 CFR

2012-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2014 CFR

2014-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development

PubMed Central

Mott, Tiffany M.; Vijayakumar, Sudhamathi; Sbrana, Elena; Endsley, Janice J.; Torres, Alfredo G.

2015-01-01

Background In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis. Methodology/Principal Findings Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 104 CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001. Conclusions/Significance Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis. PMID:26114445

Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

PubMed

Mott, Tiffany M; Vijayakumar, Sudhamathi; Sbrana, Elena; Endsley, Janice J; Torres, Alfredo G

2015-01-01

In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis. Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4) CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001. Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

[Influence of Schinus terebinthifolius Raddi (aroeira) and Carapa guianensis Aublet (andiroba) in the healing process of gastrorraphies].

PubMed

Santos, Orlando José Dos; Malafaia, Osvaldo; Ribas-Filho, Jurandir Marcondes; Czeczko, Nicolau Gregori; Santos, Rayan Haquim Pinheiro; Santos, Rennan Abud Pinheiro

2013-06-01

The gastrorraphy isolated or associated with the use of biological adhesives formed throughout the history of surgery the usual way to promote healing in gastric lesions; however, the use of herbal medicine has been increasingly employed to help the wound healing. To evaluate the wound healing caused in the stomach of rats using extract of Schinus terebinthifolius Raddi and Carapa guianensis Aublet oil. Ninety rats, adult males were divided into three groups: aroeira, andiroba and control group, which were subdivided into three subgroups of five animals according to the time of the deaths (seven, 14 and 21 days). All underwent the same surgical procedure (injury and suture the stomach) differing only to the animals in groups aroeira and andiroba that received a daily dose of 100 mg / kg of hydroalcoholic extract and oil, by gavage, while the control group received normal saline. The parameters evaluated were the macroscopic and microscopic test of resistance to air insufflation and test the traction force. All animals showed good healing of gastric and abdominal wall without infection and dehiscence. Both groups presented neighboring organs adhesions on the gastric surface. The endurance test for air insufflation showed higher average pressure within seven days and the test revealed greater traction force of rupture between seven and 14 days in groups aroeira and andiroba. The intensity of chronic inflammation revealed statistically significant differences in angiogenesis and fibroblast proliferation. The use of extract of Schinus terebinthifolius Raddi and Carapa guianensis Aublet oil favored the gastric wound healing in rats.

Doxycycline reduces nitric oxide production in guinea pig inner ears.

PubMed

Helling, Kai; Wodarzcyk, Karl; Brieger, Jürgen; Schmidtmann, Irene; Li, Huige; Mann, Wolf J; Heinrich, Ulf-Rüdiger

2011-12-01

Gentamicin application is an important therapeutic option to control vertigo spells in Ménière's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. In a prospective animal study, a single dose of gentamicin (10mg/kg body weight) was injected intratympanically into male guinea pigs (n=48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards. The organ of Corti and the lateral wall of 42 animals were isolated after 7 days and incubated separately for 6h in cell culture medium. Doxycycline was adjusted to organ cultures of 5 animals. Two NOS inhibitors, N(G)-Nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine monoacetate (l-NMMA), were applied in three different concentrations to the organ cultures of 30 animals in total (5 animals per concentration). As controls, seven animals received no further substance except gentamicin. The NO-production was quantified by chemiluminescence. Additional six gentamicin-treated animals were used for immunohistochemical studies. The ABRs declined continuously from the first to the seventh day after gentamicin application. Doxycycline reduced NO-production in the lateral wall by 54% (p=.029) comparable to the effect of the applied nitric oxide inhibitors. In the organ of Corti, NO-production was reduced by about 41% showing no statistical significance in respect to great inter-animal variations. The application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Whole genome sequencing in the search for genes associated with the control of SIV infection in the Mauritian macaque model.

PubMed

de Manuel, Marc; Shiina, Takashi; Suzuki, Shingo; Dereuddre-Bosquet, Nathalie; Garchon, Henri-Jean; Tanaka, Masayuki; Congy-Jolivet, Nicolas; Aarnink, Alice; Le Grand, Roger; Marques-Bonet, Tomas; Blancher, Antoine

2018-05-08

In the Mauritian macaque experimentally inoculated with SIV, gene polymorphisms potentially associated with the plasma virus load at a set point, approximately 100 days post inoculation, were investigated. Among the 42 animals inoculated with 50 AID 50 of the same strain of SIV, none of which received any preventive or curative treatment, nine individuals were selected: three with a plasma virus load (PVL) among the lowest, three with intermediate PVL values and three among the highest PVL values. The complete genomes of these nine animals were then analyzed. Initially, attention was focused on variants with a potential functional impact on protein encoding genes (non-synonymous SNPs (NS-SNPs) and splicing variants). Thus, 424 NS-SNPs possibly associated with PVL were detected. The 424 candidates SNPs were genotyped in these 42 SIV experimentally infected animals (including the nine animals subjected to whole genome sequencing). The genes containing variants most probably associated with PVL at a set time point are analyzed herein.

Survey of animal bite injuries and their management for an estimate of human rabies deaths in N'Djaména, Chad.

PubMed

Frey, J; Mindekem, R; Kessely, H; Doumagoum Moto, D; Naïssengar, S; Zinsstag, J; Schelling, E

2013-12-01

To estimate the annual human rabies incidence as a baseline prior to mass dog vaccination campaigns in N'Djaména, Chad. Survey of animal bites, involving 50% of all healthcare providers in N'Djaména, from September 2008 to April 2009. Of 86 people exposed to a suspected rabid animal, 50% received post-exposure vaccination and a further 8% had their wound cleaned. We estimated annual incidence of bites from suspected rabid animals of 12.9/100,000 and an incidence of 0.7 human rabies deaths/100,000, resulting in 7 estimated deaths (95% confidence interval 4-10 deaths) per year in N'Djaména. 14% of bite victims sought help from veterinarians. Closer cooperation between physicians and veterinarians warrants more effective rabies control. The high proportion (42%) of potentially exposed people without post-exposure vaccination or wound treatment necessitates urgent attention. © 2013 John Wiley & Sons Ltd.

Rabies postexposure consultations in New Zealand from 1998 to 2012.

PubMed

Shaw, Marc T M; Visser, Jenny; Edwards, Ciaran

2015-01-01

Rabies is an invariably fatal zoonotic viral disease. New Zealanders going abroad are largely unaware of the risk of contracting the disease. Prevention is the key to controlling the spread of this disease. Data from 363 individuals presenting to New Zealand travel health clinics between 1998 and 2012 for post-travel consultations on potential rabies exposure were collated retrospectively. The data focused on traveler demographics, the country and nature of exposure, the purpose of travel, and pre-travel rabies awareness. The female-to-male ratio of subject travelers presenting was almost equal (1.1 : 1 ratio, respectively); the subjects were typically between 16 and 30 years (44.6%), tourists (64.5%), traveling less than 1 month (55.3%), and likely to have been exposed to animal contact in either Thailand (31.1%), China (13.2%), or Indonesia (12.3%). The animals to which they were exposed were usually dogs (59.5%) or monkeys (28.7%). Most potential exposures were penetrating (69.9%). Injury caused by the animal was more common in the lower limbs (50%) than in the upper limbs (43.4%); 89.4% of exposures were of World Health Organization (WHO) category III. Travelers were more likely to have received pre-travel rabies advice if they had been seen by a travel medicine specialist (96.1%) compared to a general practitioner (GP) (53.3%). Sixteen percent of travelers received rabies preexposure prophylaxis. Of the subjects who were managed following exposure, 79.7% did not receive immunoglobulin when indicated, and 21.5% did not receive any vaccine. Of the travelers that did receive a vaccine, 62.5% did so on the day of exposure. Of the travelers assessed, 16.7% had traveled without insurance. New Zealanders require better guidance in understanding the need for travel-related rabies vaccination, as they are not managed abroad according to WHO guidelines. Few travelers had had pre-travel immunization, and only 20.3% of them had received WHO-advised postexposure management. Thus, 79.7% of the cohort theoretically remained at risk for contracting rabies because of inappropriate management following possible exposure to the disease. © 2014 International Society of Travel Medicine.

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

PubMed

Voronina, T A; Guzevatykh, L S; Trofimov, S S

2005-01-01

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice

PubMed Central

Montgomery, Kate L; Yeh, Alexander J; Ho, John S; Tsao, Vivien; Iyer, Shrivats Mohan; Grosenick, Logan; Ferenczi, Emily A; Tanabe, Yuji; Deisseroth, Karl; Delp, Scott L; Poon, Ada S Y

2017-01-01

To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm3) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 °C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets. PMID:26280330

Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

PubMed

Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

2017-03-09

A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone. Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

Cellular delivery of human CNTF prevents motor and cognitive dysfunction in a rodent model of Huntington's disease.

PubMed

Emerich, D F; Cain, C K; Greco, C; Saydoff, J A; Hu, Z Y; Liu, H; Lindner, M D

1997-01-01

The delivery of ciliary neurotrophic factor (CNTF) to the central nervous system has recently been proposed as a potential means of halting or slowing the neural degeneration associated with Huntington's disease (HD). The following set of experiments examined, in detail, the ability of human CNTF (hCNTF) to prevent the onset of behavioral dysfunction in a rodent model of HD. A DHFR-based expression vector containing the hCNTF gene was transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting hCNTF were transplanted bilaterally into rat lateral ventricles. Eight days later, the same animals received bilateral injections of quinolinic acid (QA, 225 nmol) into the previously implanted striata. A third group received sham surgery (incision only) and served as a normal control group. Bilateral infusions of QA produced a significant loss of body weight and mortality that was prevented by prior implantation with hCNTF-secreting cells. Moreover, QA produced a marked hyperactivity, an inability to use the forelimbs to retrieve food pellets in a staircase test, increased the latency of the rats to remove adhesive stimuli from their paws, and decreased the number of steps taken in a bracing test that assessed motor rigidity. Finally, the QA-infused animals were impaired in tests of cognitive function-the Morris water maze spatial learning task, and the delayed nonmatching-to-position operant test of working memory. Prior implantation with hCNTF-secreting cells prevented the onset of all the above deficits such that implanted animals were nondistinguishable from sham-lesioned controls. At the conclusion of behavioral testing, 19 days following QA, the animals were sacrificed for neurochemical determination of striatal choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) levels. This analysis revealed that QA decreased striatal ChAT levels by 35% and striatal GAD levels by 45%. In contrast, hCNTF-treated animals did not exhibit any decrease in ChAT levels and only a 10% decrease in GAD levels. These results support the concepts that implants of polymer-encapsulated hCNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage, produce extensive behavioral protection as a result of that neuronal sparing, and that this strategy may ultimately prove relevant for the treatment of HD.

Detecting animal by-product intake using stable isotope ratio mass spectrometry (IRMS).

PubMed

da Silva, D A F; Biscola, N P; Dos Santos, L D; Sartori, M M P; Denadai, J C; da Silva, E T; Ducatti, C; Bicudo, S D; Barraviera, B; Ferreira, R S

2016-11-01

Sheep are used in many countries as food and for manufacturing bioproducts. However, when these animals consume animal by-products (ABP), which is widely prohibited, there is a risk of transmitting scrapie - a fatal prion disease in human beings. Therefore, it is essential to develop sensitive methods to detect previous ABP intake to select safe animals for producing biopharmaceuticals. We used stable isotope ratio mass spectrometry (IRMS) for 13 C and 15 N to trace animal proteins in the serum of three groups of sheep: 1 - received only vegetable protein (VP) for 89 days; 2 - received animal and vegetable protein (AVP); and 3 - received animal and vegetable protein with animal protein subsequently removed (AVPR). Groups 2 and 3 received diets with 30% bovine meat and bone meal (MBM) added to a vegetable diet (from days 16-89 in the AVP group and until day 49 in the AVPR group, when MBM was removed). The AVPR group showed 15 N equilibrium 5 days after MBM removal (54th day). Conversely, 15 N equilibrium in the AVP group occurred 22 days later (76th day). The half-life differed between these groups by 3.55 days. In the AVPR group, 15 N elimination required 53 days, which was similar to this isotope's incorporation time. Turnover was determined based on natural 15 N signatures. IRMS followed by turnover calculations was used to evaluate the time period for the incorporation and elimination of animal protein in sheep serum. The δ 13 C and δ 15 N values were used to track animal protein in the diet. This method is biologically and economically relevant for the veterinary field because it can track protein over time or make a point assessment of animal feed with high sensitivity and resolution, providing a low-cost analysis coupled with fast detection. Isotopic profiles could be measured throughout the experimental period, demonstrating the potential to use the method for traceability and certification assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.

PubMed

Kim, Harry K W; Aruwajoye, Olumide; Du, Justin; Kamiya, Nobuhiro

2014-09-17

Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease. Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed. Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group. Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern. This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

An investigation into the use of music as potential auditory enrichment for moloch gibbons (Hylobates moloch).

PubMed

Wallace, Emma K; Kingston-Jones, Mark; Ford, Matthew; Semple, Stuart

2013-01-01

The use of music as enrichment has rarely been explored in zoos, despite evidence that music has a positive effect on a range of laboratory housed animals. In this study of moloch gibbons, Hylobates moloch, at Howletts Wild Animal Park (Kent, England), instrumental classical music was played to eight individuals in two family groups. Music was played 7 hr a day during three of six study weeks for each group, alternating with control weeks in which no music was played. In focal watches, data were recorded on a measure of activity, brachiation, and on two rates of affiliative behavior, giving and receiving grooming. In addition, to assess potential impacts on emotional state, data were recorded on self-scratching and self-grooming, two widely used indices of anxiety or stress. Analyses were carried out for each individual separately, as previous studies of primates indicate animals may differ in their response to enrichment. Results revealed little evidence for effects of music on gibbons' behavior. During the music compared to control weeks, the adult male from one group showed higher rates of self-scratching and higher durations of both self-grooming and grooming others. The adult female from the same group was groomed more during the music weeks than control weeks. For the six other animals, no significant differences in behaviors were seen between music and control conditions. Our findings suggest music may not be an effective enrichment for captive gibbons, and further highlight the importance of considering individual differences when assessing the effects of potential enrichment. Copyright © 2013 Wiley Periodicals Inc.

Protective effects of dietary selenium and vitamin C in barium-induced cardiotoxicity.

PubMed

Elwej, Awatef; Ghorbel, Imen; Chaabane, Mariem; Soudani, Nejla; Marrekchi, Rim; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Zeghal, Najiba; Sefi, Mediha

2017-11-01

Several metals including barium (Ba) known as environmental pollutants provoke deleterious effects on human health. The present work pertains to the potential ability of selenium (Se) and/or vitamin C, used as nutritional supplements, to alleviate the toxic effects induced by barium chloride (BaCl 2 ) in the heart of adult rats. Animals were randomly divided into seven groups of six each: group 1, serving as negative controls, received distilled water; group 2 received in their drinking water BaCl 2 (67 ppm); group 3 received both Ba and Se (sodium selenite 0.5 mg kg -1 of diet); group 4 received both Ba and vitamin C (200 mg kg -1 bodyweight) via force feeding; group 5 received Ba, Se, and vitamin C; and groups 6 and 7, serving as positive controls, received either Se or vitamin C for 21 days. The exposure of rats to BaCl 2 caused cardiotoxicity as monitored by an increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, a decrease in Na + -K + adenosine triphosphatase (ATPase), Mg 2+ ATPase, and acetylcholinesterase activities and in antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and nonprotein thiols). Plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels increased, while high-density lipoprotein-cholesterol level decreased. Coadministration of Se and/or vitamin C restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Se and vitamin C may be a promising therapeutic strategy for Ba-induced heart injury.

Methylene Blue Facilitates Memory Retention in Zebrafish in a Dose-Dependent Manner.

PubMed

Echevarria, David J; Caramillo, Erika M; Gonzalez-Lima, Francisco

2016-12-01

Methylene blue (MB) is an FDA-grandfathered drug with memory-enhancing effects at low doses, but opposite effects at high doses. We investigated the effects of four MB doses (0.1, 0.5, 5.0, or 10.0 μM) on zebrafish memory retention in the T-maze task. After training fish to swim into a certain arm of the T-maze, the fish were placed into a tank containing one of the four MB doses or a control tank containing blue food dye. Subsequently, fish were placed into the T-maze for memory retention testing. Results indicated that MB produced hormetic dose-response effects on memory. Fish that received the 0.5 μM dose performed significantly better at the T-maze than those that received higher doses. Fish who received 5.0 μM did not exhibit a significant difference in performance from control fish, and the fish that received the 10.0 μM dose performed significantly worse than lower doses. These findings support the utility of zebrafish in comparative research and their potential value for testing of MB and other neuropsychopharmacological treatments in animal models of memory disorders.

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

PubMed

Reddy, B S; Furuya, K; Lowenfels, A

1984-07-01

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig

PubMed Central

Choo, Daniel I.; Riazuddin, Saima; Ahmed, Zubair M.

2015-01-01

Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing. PMID:26599238

A study to compare the efficacy of polyether ether ketone rod device with titanium devices in posterior spinal fusion in a canine model.

PubMed

Wang, Nanxiang; Xie, Huanxin; Xi, Chunyang; Zhang, Han; Yan, Jinglong

2017-03-09

The benefits of posterior lumbar fusion surgery with orthotopic paraspinal muscle-pediculated bone flaps are well established. However, the problem of non-union due to mechanical support is not completely resolved. The aim of the study was to compare the efficacy of polyether ether ketone (PEEK) rod device with conventional titanium devices in the posterior lumbar fusion surgery with orthotopic paraspinal muscle-pediculated bone flaps. This was a randomized controlled study with an experimental animal model. Thirty-two mongrel dogs were randomly divided into two groups-control group (n = 16), which received the titanium device and the treatment group (n = 16), which received PEEK rods. The animals were sacrificed 8 or 16 weeks after surgery. Lumbar spines of dogs in both groups were removed, harvested, and assessed for radiographic, biomechanical, and histological changes. Results in the current study indicated that there was no significant difference in the lumbar spine of the control and treatment groups in terms of radiographic, manual palpation, and gross examination. However, certain parameters of biomechanical testing showed significant differences (p < 0.05) in stiffness and displacement, revealing a better fusion (treatment group showed decreased stiffness with decreased displacement) of the bone graft. Similarly, the histological analysis also revealed a significant fusion mass in both treatment and control groups (p < 0.05). These findings revealed that fixation using PEEK connecting rod could improve the union of the bone graft in the posterior lumbar spine fusion surgery compared with that of the titanium rod fixation.

A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T₃) in obese rats subjected to either calorie-restricted diet or hyperthyroidism.

PubMed

De Sibio, Maria Teresa; Luvizotto, Renata Azevedo Melo; Olimpio, Regiane Marques Castro; Corrêa, Camila Renata; Marino, Juliana; de Oliveira, Miriane; Conde, Sandro José; Ferreira, Ana Lúcia dos Anjos; Padovani, Carlos Roberto; Nogueira, Célia Regina

2013-01-01

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

A Comparative Genotoxicity Study of a Supraphysiological Dose of Triiodothyronine (T3) in Obese Rats Subjected to Either Calorie-Restricted Diet or Hyperthyroidism

PubMed Central

De Sibio, Maria Teresa; Luvizotto, Renata Azevedo Melo; Olimpio, Regiane Marques Castro; Corrêa, Camila Renata; Marino, Juliana; de Oliveira, Miriane; Conde, Sandro José; Ferreira, Ana Lúcia dos Anjos; Padovani, Carlos Roberto; Nogueira, Célia Regina

2013-01-01

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. PMID:23468891

[Assessment of efficiency of use of the developed supplement containing selenium on laboratory animals].

PubMed

Bazhenova, B A; Aslaliev, A D; Danilov, M B; Badmaeva, T M; Vtorushina, I A

2015-01-01

The article presents the results of a study of the effectiveness of wheat flour containing selenium in organic form. The organic form of trace element was achieved by transformation of selenium in selenium-methionine (Se-Met) at germination of wheat grains, moistened with a solution of sodium selenite. To determine the effectiveness of selenium- containing supplements experimental investigations were carried out on Long white rats with initial body weight 50 ± 2 g. The duration of the experiment was 30 days. The research model included four groups of animals: control group--animals were fed a complete vivarium diet; group 1--a model of selenium deficiency, which was achieved by feeding selenium-deficient food (grain growh in the Chita region of the Trans-Baikal Territory Zabaikalsky Krai); group 2--animals were administered selenium supplement in the form of enriched flour (0.025 µg Se per 50 g body weight of the animal) on the background of selenium-deficient diet; group 3--animals were treated with a high dose of selenium in the form of a solution of sodium selenite intragastrically through a tube (0.15 µg Se per 50 g body weight). Selenium-containing additive on the background of selenium-deficient diet had a positive impact on the appearance and behavior of animals, the body weight gain per head after 10 days in group 2 amounted to 47.9 g that was 4 fold larger than in rats of group 1. The study of selenium content showed that in the blood, liver, lungs and heart of rats treated with the additive on the background of selenium-deficient diet (group 2), selenium level did not differ from those in the control group and was within physiological norms. The experiment showed that selenium deficiency and rich in selenium rich diet has a significantly different effect on the studied parameters of oxidative-antioxidative status. The activity of blood glutathione peroxidase in animals of group 2 (did not differ from that in group 3) was almost 2 fold higher than in blood of control animals and was seven fold higher than that in blood of animals kept on selenium deficient diet (35.57 ± 3.36 µmol/g per 1 min) A similar dependence was established when studying the activity of glutathione reductase. It has been revealed thatthe oxidative-antioxidative status of animals from experimental groups 1 and 3 was lower than from control group and group 2. Thus, blood antioxidant activity in animals receiving diet with selenium deficiency and high dose of this trace element, was less than in the control group by 43.1 and 25.4%, respectively. Liver MDA level in animals kept on a diet with selenium deficiency exceeded the value of this indicator in the group 2 more than 1.5 fold (110.5 ± 10.70 vs. 72.5 ± 4.30 nmol/mg). When using selenium-containing supplement, this parameter decreased to the control level. In blood plasma of the animals of group 2 total antioxidant activity increased by about five times as compared with the indicators of animals kept on selenium-deficient diet, and was 25% higher than in control. Thus, the introduction of a selenium supplements in the deficient diet contributes to the development of endogenous antioxidants that suppress lipid oxidation. High biological effectiveness of supplements containing organic form of selenium has been proved.

Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs.

PubMed

Okuda, Takeshi; Sugahara, Kazuma; Takemoto, Tsuyoshi; Shimogori, Hiroaki; Yamashita, Hiroshi

2005-03-01

The efficacy of caspase inhibitors for protecting the cochlea was evaluated in an in vivo study using guinea pigs, as the animal model system. Gentamicin (12 mg/ml) was delivered via an osmotic pump into the cochlear perilymphatic space of guinea pigs at 0.5 microl/h for 14 days. Additional animals were given either z-Val-Ala-Asp (Ome)-fluoromethyl ketone (z-VAD-FMK) or z-Leu-Glu-His-Asp-FMK (z-LEHD-FMK), a general caspase inhibitor and a caspase 9 inhibitor, respectively, in addition to gentamicin. The elevation in auditory brain stem response thresholds, at 4, 7, and 14 days following gentamicin administration, were decreased in animals that received both z-VAD-FMK and z-LEHD-FMK. Cochlear sensory hair cells survived in greater numbers in animals that received caspase inhibitors in addition to gentamicin, whereas sensory hair cells in animals that received gentamicin only were severely damaged. These results suggest that auditory cell death induced by gentamicin is closely related to the activation of caspases in vivo.

A wireless power transmission system for implantable devices in freely moving rodents.

PubMed

Eom, Kyungsik; Jeong, Joonsoo; Lee, Tae Hyung; Kim, Jinhyung; Kim, Junghoon; Lee, Sung Eun; Kim, Sung June

2014-08-01

Reliable wireless power delivery for implantable devices in animals is highly desired for safe and effective experimental use. Batteries require frequent replacement; wired connections are inconvenient and unsafe, and short-distance inductive coupling requires the attachment of an exterior transmitter to the animal's body. In this article, we propose a solution by which animals with implantable devices can move freely without attachments. Power is transmitted using coils attached to the animal's cage and is received by a receiver coil implanted in the animal. For a three-dimensionally uniform delivery of power, we designed a columnar dual-transmitter coil configuration. A resonator-based inductive link was adopted for efficient long-range power delivery, and we used a novel biocompatible liquid crystal polymer substrate as the implantable receiver device. Using this wireless power delivery system, we obtain an average power transfer efficiency of 15.2% (minimum efficiency of 10% and a standard deviation of 2.6) within a cage of 15×20×15 cm3.

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

Synergistic effects of fenbendazole and metronidazole against Giardia muris in Swiss mice naturally infected.

PubMed

Bezagio, Renata Coltro; Colli, Cristiane Maria; Romera, Liara Izabela Lopes; Ferreira, Érika Cristina; Falavigna-Guilherme, Ana Lúcia; Gomes, Mônica Lúcia

2017-03-01

In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.

Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits.

PubMed

Labrador Velandia, Sonia; Di Lauro, Salvatore; Alonso-Alonso, Maria Luz; Tabera Bartolomé, Soraya; Srivastava, Girish Kumar; Pastor, José Carlos; Fernandez-Bueno, Ivan

2018-01-01

To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits. Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 10 6 cells/ml. Groups 3 and 6 received a high dose of 30 × 10 6 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs. There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected. MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 10 6 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.

Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption.

PubMed

Kobus, Thiele; Zervantonakis, Ioannis K; Zhang, Yongzhi; McDannold, Nathan J

2016-09-28

HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated whether we could improve the response by temporary disruption of the BBB using focused ultrasound in combination with microbubbles. To study this, we inoculated 30 nude rats with HER2-positive cells derived from a brain metastasis of a breast cancer patient (MDA-MB-361). The animals were divided into three groups: a control-group that received no treatment; an antibody-only group that received six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody group that received trastuzumab and pertuzumab in combination with six weekly sessions of BBB disruption using focused ultrasound. In two animals, the leakiness of the tumors before disruption was evaluated using contrast-enhanced T1-weighted magnetic resonance imaging and found that the tumors were not leaky. The same technique was used to evaluate the effectiveness of BBB disruption, which was successful in all sessions. The tumor in the control animals grew exponentially with a growth constant of 0.042±0.011mm(3)/day. None of the antibody-only animals responded to the treatment and the growth constant was 0.033±0.009mm(3)/day during the treatment period. Four of the ten animals in the ultrasound+antibody-group showed a response to the treatment with an average growth constant of 0.010±0.007mm(3)/day, compared to a growth constant 0.043±0.013mm(3)/day for the six non-responders. After the treatment period, the tumors in all groups grew at similar rates. As the tumors were not leaky before BBB disruption and there were no responders in the antibody-only group, these results show that at least in some cases disruption of the BBB is necessary for a response to the antibodies in these brain metastases. Interestingly, only some of the rats responded to the treatment. We did not observe a difference in tumor volume at the start of the treatment, nor in HER2 expression or in contrast-enhancement on MRI between the responders and non-responders to explain this. Better understanding of why certain animals respond is needed and will help in translating this technique to the clinic. In conclusion, we demonstrate that BBB disruption using focused ultrasound in combination with antibody therapy can inhibit growth of breast cancer brain metastasis. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung gas volumes and expiratory time constant in immature newborn rabbits treated with natural or synthetic surfactant or detergents.

PubMed

Bongrani, S; Fornasier, M; Papotti, M; Razzetti, R; Robertson, B

1994-01-01

Immature newborn rabbits delivered at a gestational age of 27 days were tracheotomized and treated, via the tracheal cannula, with clinically recommended doses of natural or synthetic surfactant (Curosurf and Exosurf, respectively). Littermates received 0.1% tyloxapol, 5% Tween 20, or saline. The dose volume of Curosurf was 2.5 ml/kg, that of the other materials 5 ml/kg. Animals were kept in a multiplethysmograph system and ventilated for 30 min with a standardized sequence of insufflation pressures. End-expiratory lung gas volume was calculated at the end of the experiment from measurements of lung weight and total lung volume. Tidal volumes were significantly improved in all groups of animals receiving surfactant or detergents. However, expiratory time constant (determined from the tidal volume tracing) was significantly longer, and end-expiratory gas volume significantly larger, in animals treated with Curosurf than in those receiving Exosurf or detergents. These differences were confirmed by semiquantitative evaluation of alveolar air expansion in histological sections. In addition, airway epithelial necrosis was reduced in animals receiving Curosurf, Exosurf, or Tween 20, but not in animals treated with tyloxapol. The discrepancy between improvements in tidal volume, expiratory time constant, and end-expiratory gas volume reflects failure of lung stabilization in animals treated with Exosurf or detergents, probably due to absence of specific hydrophobic proteins in the synthetic products.

Interleukin-13 protects mouse intestine from ischemia and reperfusion injury through regulation of innate and adaptive immunity.

PubMed

Farmer, Douglas G; Ke, Bibo; Shen, Xiu-Da; Kaldas, Fady M; Gao, Feng; Watson, Melissa J; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W

2011-04-15

Ischemia-reperfusion (I/R) injury is a major factor leading to intestinal dysfunction or graft loss after intestinal surgery or transplantation. This study investigated the cytoprotective effects and putative mechanisms of interleukin (IL)-13 after intestinal I/R injury in the mouse. Mouse warm intestinal I/R injury induced by clamping the superior mesenteric artery for 100 min with tissue analysis at 4 and 24 hr after reperfusion. Treated animals received intravenous recombinant murine IL-13 (rIL-13) and anti-IL-13 antibody, whereas controls received saline. rIL-13 administration markedly prolonged animal survival (100% vs. 50% in saline controls) and resulted in near normal histopathological architecture. rIL-13 treatment also significantly decreased myeloperoxidase activity. Mice conditioned with rIL-13 had a markedly depressed Toll-like receptor-4 expression and increased the expression of Stat6, antioxidant hemeoxygenase-1, and antiapoptotic A20, Bcl-2/Bcl-xl, compared with that of controls. Unlike in controls, the expression of mRNA coding for IL-2/interferon-γ, and interferon-γ-inducible protein (IP)-10/monocyte chemotactic protein-1 remained depressed, whereas that of IL-13/IL-4 reciprocally increased in the mice treated with rIL-13. Administration of anti-IL13 antibody alone or in combination with rIL-13 resulted in outcomes similar to that seen in controls. This study demonstrates for the first time that IL-13 plays a protective role in intestinal warm I/R injury and a critical role in the regulation of Stat6 and Toll-like receptor-4 signaling. The administration of IL-13 exerts cytoprotective effects in this model by regulating innate and adaptive immunity while the removal of IL-13 using antibody therapy abrogates this effect.

Effect of different doses of nandrolone decanoate on lipid peroxidation, DNA fragmentation, sperm abnormality and histopathology of testes of male Wister rats.

PubMed

Mohamed, Hanaa Mahmoud; Mohamed, Manal Abdul-Hamid

2015-01-01

The present study aims of to investigate the effects of low and high doses of nandrolone decanoate (ND) on histopathology and apoptosis of the spermatogenic cells as well as lipid peroxidation, antioxidant enzyme activities, sperm abnormality and DNA fragmentation. Eighteen animals were divided into three groups each group contain six animals. The rats were divided into three groups as following: Group 1 was administered saline (control). Group 2, received nandrolone decanoate (3 mg/kg/weekly) (low dose) with intramuscular injection. Group 3, received intramuscular injection dose of nandrolone decanoate (10 mg/kg/weekly) (high dose). After 8 weeks, caspase-3 assay was used to determine the apoptotic cells. The sperm parameters, lipid peroxidation, antioxidant enzyme activities and testosterone concentration were also investigated in the experimental groups of both low and high dose compared to the control groups. Treated group with high dose showed degenerated germinal epithelial cells sloughed in the lumina of seminiferous tubules, where almost seminiferous tubules were devoid of spermatids and spermatozoa compared to control and group treated with low dose. Also, a significant increase of lipid peroxidation levels and heat shock proteins was observed in two groups administrated with two different doses of ND while, antioxidant enzyme activities, and testosterone concentration was significantly decreased in two treated group when compared with control. Administration of ND at high and low doses leads to deteriorated sperm parameters, DNA fragmentation and testicular apoptosis. In conclusion, the administration ND at high doses more effective on lipid peroxidation, antioxidant enzyme activities, sperm abnormality, histopathology, apoptotic and DNA changes compared to low dose group and to control group. Published by Elsevier GmbH.

Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior

PubMed Central

Acerbo, Martin J.; Johnson, Alan Kim

2011-01-01

Behavioral sensitization involves increases in the magnitude of a response to a stimulus after repeated exposures to the same response initiator. Administration of psychomotor stimulants and the induction of appetitive motivational states associated with natural reinforcers like sugar and salt are among experimental manipulations producing behavioral sensitization. In rats, repeated administration of the mineralocorticoid agonist deoxycorticosterone acetate (DOCA) initially induces incremental increases in daily hypertonic saline consumption (i.e., sensitization of sodium appetite) in spite of the retention of sodium. The present studies investigated whether sodium appetite sensitization induced by DOCA shares mechanisms similar to those of psychomotor stimulant-induced sensitization, and whether there is evidence for reciprocal cross-sensitization. In Experiments 1 and 3, rats received control or cocaine treatments to induce locomotor sensitization. A week later DOCA (or vehicle) was administered to generate a sodium appetite. Animals pretreated with cocaine showed a greater sodium appetite. In Experiment 2, the order of the putative sensitizing treatments was reversed. Rats first received either a series of DOCA or vehicle treatments either with or without access to saline and were later tested for sensitization of the locomotor response to cocaine. Animals pretreated with DOCA without access to saline showed greater locomotor responses to cocaine than animals receiving vehicle treatments. Together these experiments indicate that treatments generating a sustained salt appetite and producing cocaine-induced psychomotor responses show reciprocal behavioral cross-sensitization. The underlying mechanisms accounting for this relationship may be the fact that psychostimulants and an unresolved craving for sodium can act as potent stressors. PMID:21352848

Photobiomodulation reduces oral mucositis by modulating NF-kB

NASA Astrophysics Data System (ADS)

Curra, Marina; Pellicioli, Ana Carolina Amorim; Filho, Nélson Alexandre Kretzmann; Ochs, Gustavo; Matte, Úrsula; Filho, Manoel Sant'Ana; Martins, Marco Antonio Trevizani; Martins, Manoela Domingues

2015-12-01

The aim of this study was to evaluate NF-kB during 5-fluorouracil (FU)-induced oral mucositis and ascertain whether photobiomodulation (PBM), as a preventive and/or therapeutic modality, influences this transcription factor. Ninety-six male golden Syrian hamsters were allocated into four groups: control (no treatment); PBM therapeutic, PBM preventive, and PBM combined. Animals received an injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched. Irradiation was carried out using a 660-nm, 40-mW diode laser at 6 J/cm2 during 6 s/point, 0.24 J/point, for a total dose of 1.44 J/day of application. Animals were euthanized on days 0, 5, 10, and 15 (n=6). Buccal mucosa was removed for protein quantification by Western blot. Clinical analysis revealed that PBM groups exhibited less mucositis than controls on day 10. Control animals exhibited lower levels of NF-kB during mucositis development and healing. The preventive and combined protocols were associated with higher NF-kB levels at day 5; however, the therapeutic group had higher levels at days 10 and 15. These findings suggest that the preventive and/or therapeutic PBM protocols reduced the severity of oral mucositis by activating the NF-kB pathway.

Fostering understanding of multimedia messages through pre-training: evidence for a two-stage theory of mental model construction.

PubMed

Mayer, Richard E; Mathias, Amanda; Wetzell, Karen

2002-09-01

Students received a narrated animation explaining the workings of a car's braking system (Experiments 1 and 2) or a bicycle tire pump (Experiment 3) and then took retention and transfer tests. Some students received pre-training concerning each of the components in the system before receiving the narrated animation (pre-training group), whereas others received no pre-training (no pre-training group) or--only in Experiment 3--training after the narrated animation (post-training group). The pre-training described or depicted the possible states of each part. Students in the pre-training group performed better than did students in other groups on tests of transfer (in all 3 experiments) and retention (in Experiments 1 and 2). Results are consistent with a 2-stage theory of mental model construction.

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

PubMed

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

2013-02-01

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

Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat.

PubMed

Wolf, Rainer; Dobrowolny, Henrik; Nullmeier, Sven; Bogerts, Bernhard; Schwegler, Herbert

2017-03-30

The role of the thalamus in schizophrenia has increasingly been studied in recent years. Deficits in the ventral thalamus have been described in only few postmortem and neuroimaging studies. We utilised our previously introduced neurodevelopmental animal model, the neonatal excitotoxic lesion of the ventral thalamus of Sprague-Dawley rats (Wolf et al., Pharmacopsychiatry 43:99-109, 22). At postnatal day (PD7), male pubs received bilateral thalamic infusions with ibotenic acid (IBA) or artificial cerebrospinal fluid (control). In adulthood, social interaction of two animals not familiar to each other was studied by a computerised video tracking system. This study displays clear lesion effects on social interaction of adult male rats. The significant reduction of total contact time and the significant increase in distance between the animals in the IBA group compared to controls can be interpreted as social withdrawal modelling a negative symptom of schizophrenia. The significant increase of total distance travelled in the IBA group can be hypothesised as agitation modelling a positive symptom of schizophrenia. Using a triple concept of social interaction, the percentage of no social interaction (Non-SI%) was significantly larger, and inversely, the percentage of passive social interaction (SI-passive%) was significantly smaller in the IBA group when compared to controls. In conclusion, on the background of findings in schizophrenic patients, the effects of neonatal ventral thalamic IBA lesions in adult male rats support the hypothesis of face and construct validity as animal model of schizophrenia.

Protection of farm goats by combinations of recombinant peptides and formalin inactivated spores from a lethal Bacillus anthracis challenge under field conditions.

PubMed

Koehler, Susanne M; Buyuk, Fatih; Celebi, Ozgur; Demiraslan, Hayati; Doganay, Mehmet; Sahin, Mitat; Moehring, Jens; Ndumnego, Okechukwu C; Otlu, Salih; van Heerden, Henriette; Beyer, Wolfgang

2017-07-12

Bacillus (B.) anthracis, the causal agent of anthrax, is effectively controlled by the Sterne live spore vaccine (34F2) in animals. However, live spore vaccines are not suitable for simultaneous vaccination and antibiotic treatment of animals being at risk of infection in an outbreak situation. Non-living vaccines could close this gap. In this study a combination of recombinant protective antigen and recombinant Bacillus collagen-like antigen (rBclA) with or without formalin inactivated spores (FIS), targeted at raising an immune response against both the toxins and the spore of B. anthracis, was tested for immunogenicity and protectiveness in goats. Two groups of goats received from local farmers of the Kars region of Turkey were immunized thrice in three weeks intervals and challenged together with non-vaccinated controls with virulent B. anthracis, four weeks after last immunization. In spite of low or none measurable toxin neutralizing antibodies and a surprisingly low immune response to the rBclA, 80% of the goats receiving the complete vaccine were protected against a lethal challenge. Moreover, the course of antibody responses indicates that a two-step vaccination schedule could be sufficient for protection. The combination of recombinant protein antigens and FIS induces a protective immune response in goats. The non-living nature of this vaccine would allow for a concomitant antibiotic treatment and vaccination procedure. Further studies should clarify how this vaccine candidate performs in a post infection scenario controlled by antibiotics.

rROP2 from Toxoplasma gondii as a potential vaccine against oocyst shedding in domestic cats.

PubMed

Zulpo, Dauton Luiz; Igarashi, Michelle; Sammi, Ana Sue; Santos, Joeleni Rosa Dos; Sasse, João Pedro; Cunha, Ivo Alexandre Leme da; Taroda, Alessandra; Barros, Luiz Daniel de; Almeida, Jonatas Campos de; Jenkins, Mark Christopher; Navarro, Italmar Teodorico; Garcia, João Luis

2017-01-01

The aim of the present study was to evaluate oocyst shedding in cats immunized by nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus) were divided in three groups G1, G2 and G3 (n=4). Animals from G1 received 100 μg of rROP2 proteins plus 20 μg of Quil-A, G2 received 100 μg of BSA plus 20 μg of Quil-A, and the G3 only saline solution (control group). All treatments were done by intranasal route at days 0, 21, 42, and 63. The challenge was performed in all groups on day 70 with ≅ 800 tissue cysts of ME-49 strain by oral route. Animals from G1 shed less oocysts (86.7%) than control groups. ELISA was used to detect anti-rROP2 IgG and IgA, however, there were no correlation between number of oocyst shedding by either IgG or IgA antibody levels. In the present work, in spite of lesser oocysts production in immunized group than control groups, it was not possible to associate the use of rROP2 via nostrils with protection against oocyst shedding. For the future, the use of either other recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to try improving the efficacy of this kind of vaccine.

The effect of caffeine on orthodontic tooth movement in rats

PubMed Central

Shirazi, Mohsen; Vaziri, Hamed; Salari, Behzad; Motahhari, Pouria; Etemad-Moghadam, Shahroo; Dehpour, Ahmad Reza

2017-01-01

Objective(s): to determine the effect of different doses of caffeine on orthodontic tooth movement (OTM) in rats. Materials and Methods: Forty male 250-300 g Sprague-Dawley rats were randomly divided into four groups of ten animals each and received 0 (control), 1 g/l, 2 g/l and 3 g/l caffeine in tap water for 3 days. Orthodontic appliances were ligated between the maxillary first molars and incisors on the 4th day of the study period. All rats were sacrificed after 2 weeks of treatment after which OTM was measured. Hematoxylin/eosin-stained sections of the molars were prepared and the mesial roots were examined for resorption-lacunae depth and osteoclast number. ANOVA was used for statistical analysis (P<0.05). Results: A significant decrease in OTM was observed only in the 2 g/l (P=0.043) and 3 g/l (P<0.01) caffeine-receiving rats compared to the control animals. Osteoclast counts and resorption-lacunae depths demonstrated significant differences between each of the caffeine groups and control rats (P<0.05). None of the variables showed significant differences between the caffeine groups (P>0.05). Conclusion: According to our findings, one of the effects of caffeine consumption during orthodontic treatment in rats was decreased root resorption. Additionally, concentrations of 2 g/l and 3 g/l inhibited OTM which seems to be due to its influence on osteoclast numbers. PMID:28392897

The quality of meat from sheep treated with tannin- and saponin-based remedies as a natural strategy for parasite control.

PubMed

Brogna, D M R; Tansawat, R; Cornforth, D; Ward, R; Bella, M; Luciano, G; Priolo, A; Villalba, J

2014-02-01

Lambs were assigned to four groups of seven and treated as follows for 12 days: control group (BP) was fed beet pulp; group T (tannin remedy) received the BP diet including 80 g/kg of quebracho extract; group S (saponin remedy) received the BP diet including 15 g/kg of quillaja extract; and group C had a free choice between T and S remedies. Lipid oxidation was lower in meat from S lambs compared to T lambs (P<0.05). Among the volatile compounds, lactate was lower in meat from S lambs compared to T animals (P=0.05). Metabolomic analysis showed that the T treatment increased ribose, fructose, glucose and sorbitol concentration in meat (P<0.05), while cholesterol was decreased by S and C treatments. The T treatment increased the concentration of C14:1 cis-9 (P<0.05). These findings indicate that treatments for parasite control containing tannins and saponins do not detrimentally affect sheep meat quality. © 2013.

Habituation and desensitization as methods for reducing fearful behavior in singly housed rhesus macaques.

PubMed

Clay, Andrea W; Bloomsmith, Mollie A; Marr, M Jackson; Maple, Terry L

2009-01-01

Operant conditioning using positive reinforcement techniques has been used extensively in the management of nonhuman primates in both zoological and laboratory settings. This research project was intended to test the usefulness of counter-conditioning techniques in reducing the fear-responses of singly housed male rhesus macaques living in the laboratory environment. A total of 18 male rhesus macaques (Macaca mulatta) were selected for this project and randomly assigned to one of three groups: a desensitization training group, a husbandry training group, or a control group. Behavioral data were collected before and after a 6 weeks training and/or habituation period during which the first two groups received a total of 125 min of positive reinforcement training (and also were assumed to undergo habituation to the environment) and the control group experienced only simple habituation to the environment. Based on a Wilcoxon Matched-Pairs Sign Test, we found that a significant proportion of animals exposed to desensitization training showed a reduction in the rate at which they engaged in cringing toward humans (exact significance=0.016, one-tailed, N-ties=6), cringing in general (exact significance=0.016, one-tailed, N-ties=6), and in stress-related behaviors (exact significance=0.016, one-tailed, N-ties=6). This was not the case for animals exposed to basic husbandry training or animals in the control group. A significant proportion of desensitization-exposed animals also showed a reduction in the duration of time spent cringing toward humans (exact significance=0.016, one-tailed, N-ties=6), but not in cringing behaviors in general or in stress-related behaviors. There were not a significant proportion of animals in either the husbandry training group or the control group that showed a decrease in duration of these behaviors. Results of this study could enhance both laboratory animal welfare and laboratory animal research, and could be a first step in developing techniques for reducing fearful behavior in rhesus monkeys in the laboratory environment. (c) 2008 Wiley-Liss, Inc.

Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat.

PubMed

Rocha, Angelica; Valles, Rodrigo; Hart, Nigel; Bratton, Gerald R; Nation, Jack R

2008-06-01

Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of the reinforcement efficacy of methamphetamine in animals perinatally exposed to lead, as compared to control animals.

Physiological Anatomical Rodent Experiment (PARE) .04 feasibility test 2

NASA Technical Reports Server (NTRS)

Burden, Hubert W.

1994-01-01

The objective of this feasibility study was to subject pregnant rats of the same age, strain, and size that will be utilized in a shuttle flight experiment to all flight conditions except the unique microgravity of space flight and determine the feasibility of the proposed experimental design to meet the experimental objectives. The study utilized facilities at NASA, Ames Research Center, Moffett Field, CA to subject the rats to the gravitational stresses of a simulated shuttle launch and simulated shuttle landing. One hundred pregnant rats were received on gestation day (G) 2 (day 1 = day of vaginal sperm) and on G7, eighty rats were laparotomized to determine the condition of pregnancy and allow assignment to test groups. The five test groups (N=10 each group) were as follows: Group 1, Nominal Flight; Group 2, Laparotomy Control; Group 3, Hysterectomy Control; Group 4, Vivarium Control; Group 5, Delayed Recovery. On G9, animals in groups 1,2,3, and 5 were subjected to a shuttle launch simulation. On G18, groups 1,2, and 3 were subjected to a shuttle landing simulation and on this same day groups 1 and 2 were subjected to unilateral hysterectomy to obtain fetuses and placentas for evaluation. Fetal crown-rump length and fetal weight of the Nominal Flight group was significantly less than the Laparotomy Control group, but placentas were similar. On G20, group 5 was subjected to a shuttle landing simulation and on this day this group received a unilateral hysterectomy and fetuses and placentas were weighed. Animals in all groups were allowed to go to term and all animals delivered between 06:00 hours G22 and 18:00 hours G23. After delivery, a blood sample was taken from each experimental dam, and they were euthanized and the thymus and adrenal glands weighed. The thymus weight from all experimental group dams was decreased relative to the Vivarium Control group but adrenal glands and hormone values in dam plasma was similar in all groups. Pups from experimental groups were tattooed for identification, the anogenital distance of male pups was measured, and all pups placed with foster dams and litter sizes were standardized to 10. There was no difference in anogenital distances between male pups from different test groups. Pups delivered from Delayed Recovery animals were smaller than pups delivered from Nominal Flight animals. On neonatal day 7, all pups were euthanized and pup adrenal glands and thymus weighed. There was no difference in weights of thymus and adrenal glands in pups euthanized at neonatal day 7. Collectively, these data confirm the feasibility of the experimental design to meet objectives of the studies proposed for shuttle flight.

Evaluation of micro-GPS receivers for tracking small-bodied mammals

PubMed Central

Shipley, Lisa A.; Forbey, Jennifer S.; Olsoy, Peter J.

2017-01-01

GPS telemetry markedly enhances the temporal and spatial resolution of animal location data, and recent advances in micro-GPS receivers permit their deployment on small mammals. One such technological advance, snapshot technology, allows for improved battery life by reducing the time to first fix via postponing recovery of satellite ephemeris (satellite location) data and processing of locations. However, no previous work has employed snapshot technology for small, terrestrial mammals. We evaluated performance of two types of micro-GPS (< 20 g) receivers (traditional and snapshot) on a small, semi-fossorial lagomorph, the pygmy rabbit (Brachylagus idahoensis), to understand how GPS errors might influence fine-scale assessments of space use and habitat selection. During stationary tests, microtopography (i.e., burrows) and satellite geometry had the largest influence on GPS fix success rate (FSR) and location error (LE). There was no difference between FSR while animals wore the GPS collars above ground (determined via light sensors) and FSR generated during stationary, above-ground trials, suggesting that animal behavior other than burrowing did not markedly influence micro-GPS errors. In our study, traditional micro-GPS receivers demonstrated similar FSR and LE to snapshot receivers, however, snapshot receivers operated inconsistently due to battery and software failures. In contrast, the initial traditional receivers deployed on animals experienced some breakages, but a modified collar design consistently functioned as expected. If such problems were resolved, snapshot technology could reduce the tradeoff between fix interval and battery life that occurs with traditional micro-GPS receivers. Our results suggest that micro-GPS receivers are capable of addressing questions about space use and resource selection by small mammals, but that additional techniques might be needed to identify use of habitat structures (e.g., burrows, tree cavities, rock crevices) that could affect micro-GPS performance and bias study results. PMID:28301495

Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).

PubMed

Raskovic, Aleksandar; Gavrilovic, Maja; Jakovljevic, Vida; Sabo, Jan

2004-01-01

The study was concerned with the effect of mice pretreatment with two commercial products of Stevia rebaudiana Bertoni on the blood glucose concentration. One group of mice was pretreated four days with 200 mg/kg of Stevita (Stevita Co, INC, Arlington Texas) (stevia) and the other with 20 mg/kg of Clear Steviosides liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), whereas the animals of control group received at the same time physiological solution. Blood glucose concentration was measured before pretreatment and four days after that. The changes in glucose level were provoked by glucose-tolerance test (500 mg/kg, p.o.) and subcutaneous injection of adrenaline (0.2 mg/kg). The same procedure of measuring blood glucose was applied on the mice with alloxan-induced diabetes mellitus (two doses of 100 mg/kg with a 24-hour interval). Blood glucose levels in mice pretreated with stevia and stevioside were lower compared with control (7.82:6.82:8.01). Also, a smaller increase in this parameter compared to control was registered with pretreated mice in the glucose-tolerance test, pretreatment with stevioside being again more effective (8.68:6.36:5.82). Pretreatment with stevioside caused no significant increase in blood glucose concentration after administering adrenaline, which was not the case with the animals pretreated with stevia and control. Pretreatment with stevia, and to a greater extent with stevioside, protected test animals from the toxic action of alloxan compared with controls.

76 FR 9319 - Notice of Request for Reinstatement of an Information Collection; National Animal Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... Collection; National Animal Health Monitoring System; Feedlot 2011 Study AGENCY: Animal and Plant Health... National Animal Health Monitoring Feedlot 2011 Study. DATES: We will consider all comments that we receive.... SUPPLEMENTARY INFORMATION: Title: National Animal Health Monitoring System; Feedlot 2011 Study. OMB Number: 0579...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

45 CFR 63.33 - Treatment of animals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Treatment of animals. 63.33 Section 63.33 Public... animals. If animals are utilized in any project receiving assistance, the applicant for such assistance shall provide assurances satisfactory to the Assistant Secretary that such animals will be provided with...

Use of the feed additive sodium hexametaphosphate to prevent dental calculus in squirrel monkeys (Saimiri spp.).

PubMed

Brady, A G; Williams, L E; Haught, D; Abee, C R

2000-03-01

Dental calculus and associated periodontal disease are serious clinical problems in captive squirrel monkeys. Calculus begins to appear as early as 2 years of age, with subsequent development of periodontal disease, dental abscessation, tooth loss and other sequelae. When used as a feed additive, sodium hexametaphosphate (HMP) retards the growth of calculus on previously cleaned teeth in rhesus monkeys, lemurs, and other species. We wanted to determine whether HMP would reduce dental calculus in squirrel monkeys (Saimiri spp.) whose teeth had not been pre-cleaned. The study animals were divided into two groups. One received a standard diet; the other received an identical diet containing the HMP additive at a concentration effective in other primate and non-primate species that had received dental cleaning prior to treatment with HMP. Teeth were graded for extent of calculus formation at the start of the study and at 3 and 6 months during HMP treatment. We compared the results from the two groups both by total score per animal and according to tooth type (e.g., incisors versus incisors in test and control groups). At the end of 6 months, dental calculus did not differ significantly between the experimental groups. Therefore, we conclude that HMP is ineffective in squirrel monkeys with preexisting dental calculus.

Prevalence of Escherichia coli O157:H7 and performance by beef feedlot cattle given Lactobacillus direct-fed microbials.

PubMed

Brashears, M M; Galyean, M L; Loneragan, G H; Mann, J E; Killinger-Mann, K

2003-05-01

Fecal shedding of Escherichia coli O157:H7, the prevalence of Escherichia coli O157:H7 in pens and on carcasses and hides, and cattle performance as a result of daily dietary supplementation with Lactobacillus-based direct-fed microbials (DFMs) were evaluated in a feeding trial involving 180 beef steers. Steers were evaluated for shedding of E. coli O157:H7 by an immunomagnetic separation technique on arrival at the feedlot, just before treatment with the DFMs, and every 14 days thereafter until slaughter. Composite pen fecal samples were collected every 14 days (alternating weeks with animal testing), and prevalence on hides and carcasses at slaughter was also evaluated. Feedlot performance (body weight gain and feed intake) was measured for the period during which the DFMs were fed. Gain efficiency was calculated as the ratio of weight gain to feed intake. Lactobacillus acidophilus NPC 747 decreased (P < 0.01) the shedding of E. coli O157:H7 in the feces of individual cattle during the feeding period. E. coli O157:H7 was approximately twice as likely to be detected in control animal samples as in samples from animals receiving L. acidophilus NPC 747. In addition, DFM supplementation decreased (P < 0.05) the number of E. coli O157:H7-positive hide samples at harvest and the number of pens testing positive for the pathogen. Body weight gains (on a live or carcass basis) and feed intakes during the DFM supplementation period did not differ among treatments. Gain efficiencies on a live-weight basis did not differ among treatments, but carcass-based gain/feed ratios tended (P < 0.06) to be better for animals receiving the two DFM treatments than for control animals. The results of this study suggest that the feeding of a Lactobacillus-based DFM to cattle will decrease, but not eliminate, fecal shedding of E. coli O157:H7, as well as contamination on hides, without detrimental effects on performance.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

PubMed

Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

2014-10-01

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

77 FR 36581 - Notice of Permit Applications Received Under the Antarctic Conservation Act of 1978

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... Conservation Act of 1978 AGENCY: National Science Foundation. ACTION: Notice of Permit Applications Received.... The presence of these animals pose operation safety concerns as well as potential harm to the animals... for capturing Antarctic fishes to study their physiology and biochemistry. Benthic Otter trawling is...

Effect of low frequency electrical stimulation on seizure-induced short- and long-term impairments in learning and memory in rats.

PubMed

Esmaeilpour, Khadijeh; Sheibani, Vahid; Shabani, Mohammad; Mirnajafi-Zadeh, Javad

2017-01-01

Kindled seizures can impair learning and memory. In the present study the effect of low-frequency electrical stimulation (LFS) on kindled seizure-induced impairment in spatial learning and memory was investigated and followed up to one month. Animals were kindled by electrical stimulation of hippocampal CA1 area in a semi-rapid manner (12 stimulations per day). One group of animals received four trials of LFS at 30s, 6h, 24h, and 30h following the last kindling stimulation. Each LFS trial was consisted of 4 packages at 5min intervals. Each package contained 200 monophasic square wave pulses of 0.1ms duration at 1Hz. The Open field, Morris water maze, and novel object recognition tests were done 48h, 1week, 2weeks, and one month after the last kindling stimulation respectively. Kindled animals showed a significant impairment in learning and memory compared to control rats. LFS decreased the kindling-induced learning and memory impairments at 24h and one week following its application, but not at 2week or 1month after kindling. In the group of animals that received the same 4 trials of LFS again one week following the last kindling stimulation, the improving effect of LFS was observed even after one month. Obtained results showed that application of LFS in fully kindled animals has a long-term improving effect on spatial learning and memory. This effect can remain for a long duration (one month in this study) by increasing the number of applied LFS. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of the europium tetracycline complex as a biomarker for atherosclerosis

NASA Astrophysics Data System (ADS)

Courrol, Lilia C.; da Silva, Mônica N.; Sicchieri, Leticia B.

2016-04-01

Atherosclerosis is a narrowing of the arteries caused by an increase of atheromatous plaque: material formed by macrophage cells containing cholesterol and fatty acids, calcium and a variable amount of fibrous connective tissue. The elation between vulnerable plaques and cardiovascular events can be determined using plaque biomarkers. In this work, atherosclerotic plaques stained with different molar ratios of europium, in a potential plaque biomarker, europium tetracycline complex, were studied by fluorescence microscopy. The tetracycline antibiotic used was chlortetracycline. The growth of atherosclerotic plaque was followed during 60 days in New Zealand rabbits divided in two groups: an experimental group (EG), with nine animals and a control group (CG) with three animals. The animals in the EG received a diet with 1% of cholesterol and the animals of GC received a normal diet. The aortic arch of the animals with 60 days were cut in the vertical plane in 6 μm thick slices, which were mounted on glass slides and stained with hematoxylin an eosin and europium chlortetracycline complex (EuCTc). The fluorescence images were obtained exciting the EuCTc absorption band with a filter cube D (BP 355 - 425) and the emission was collected with a LP 470 suppression filter. Light intensity, detector gain and acquisition time were fixed for comparisons. The 20× magnified images were collected with 12 bit (or 4096 gray tones) resolution. The mean value of gray scale for each molar ratio of EuCTc was different, indicating that the complex interacts with the components of atherosclerotic plaque and the best molar ratio was 1.5 EuCTc. These results indicate the potential use of the EuCTc biomarker for atherosclerotic plaque characterization.

Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.

PubMed

Sugano, M; Makino, N; Sawada, S; Otsuka, S; Watanabe, M; Okamoto, H; Kamada, M; Mizushima, A

1998-02-27

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits.

[Effect of epsilon-aminocaproic acid, cyclophosphamide and their combination on the growth of autochthonous sarcomas of mice induced by benzo(a)pyrene].

PubMed

Anikin, I V; Tyndyk, M L; Zabezhinskiĭ, M A; Popovich, I G; Anisimov, V N; Pliss, G B

2014-01-01

Antifibrinolytic drug epsilon-aminocaproic acid as a therapeutic form (5% solution in saline) was tested for antitumor activity in the autochthonous subcutaneous tumors of mice, induced by benzo (a) pyrene, in monotherapy mode (instead animals received drinking water) and in combination with cyclophosphamide, which was administered once intraperitoneally in the dose of 200 mg/kg. In the control groups, treated with drinking water and saline solution instead of water, there was no stabilization and reduction in tumor volume, while in the groups receiving epsilon-aminocaproic acid, cyclophosphamide and their combination statistically significantly in comparison with the control groups there was increased the proportion of tumors with not changed or reduced volume; epsilon-aminocaproic acid enhanced the antitumor effect of cyclophosphamide. The data obtained are for further study of the antitumor effect of epsilon-aminocaproic acid.

Irradiated larval vaccination of ponies against strongylus vulgaris.

PubMed

Klei, T R; Torbert, B J; Chapman, M R; Ochoa, R

1982-08-01

Nonimmune pony foals 9 to 12 mo of age were vaccinated with third-stage Strongylus vulgaris larvae (L3) irradiated with 70, 100, or 130 Kr of gamma radiation. Ponies receiving per os inoculations of L3 irradiated with 70 or 100 Kr were protected from the clinical disease and lesions associated with challenge infections of 4,300 L3, when compared to nonvaccinated controls. Similarly, the numbers of worms from the challenging population recovered from successfully vaccinated animals were significantly lower than from nonvaccinated controls. The degree of resistance that develops in individuals can be semiquantitated based on clinical and pathological responses.

TOXICOLOGY AND TREATMENT: MEDICAL AUTHORITIES AND SNAKE-BITE IN THE MIDDLE AGES.

PubMed

Walker-Meikle, Kathleen

2014-12-01

By end of the thirteenth century, surgeons and university-trained physicians in Western Europe had a plethora of authorities from the Greco-Roman and Arabic tradition from which to consult for the treatment of snake-bites. Venomous animals receive the largest share of attention in the literature on biting animals. Nearly all of the sources focus on the idea of the animal biting or puncturing the skin's surface with their mouths and few poisonous animals where the venom is passed on through the skin or hairs are mentioned. Venomous animals frequently appear in discussions on poisons in general, with poisons of animal, mineral or vegetable origin. The bulk of the discourse dealt with venomous snakes and rabid dogs, the latter considered venomous due to its 'poisonous' saliva, and to a lesser extent, scorpions and spiders. In general the bites of non-venomous animals received scant attention. Unlike modern taxonomical categories, medieval categories for animals were usually connected to the movement or the locale of the animal: flying animals, animals in water, land animals (which mainly covered quadrupeds), and crawling animals. It is in the latter category that snakes were located, along with lizards.

TOXICOLOGY AND TREATMENT: MEDICAL AUTHORITIES AND SNAKE-BITE IN THE MIDDLE AGES

PubMed Central

WALKER-MEIKLE, KATHLEEN

2015-01-01

By end of the thirteenth century, surgeons and university-trained physicians in Western Europe had a plethora of authorities from the Greco-Roman and Arabic tradition from which to consult for the treatment of snake-bites. Venomous animals receive the largest share of attention in the literature on biting animals. Nearly all of the sources focus on the idea of the animal biting or puncturing the skin’s surface with their mouths and few poisonous animals where the venom is passed on through the skin or hairs are mentioned. Venomous animals frequently appear in discussions on poisons in general, with poisons of animal, mineral or vegetable origin. The bulk of the discourse dealt with venomous snakes and rabid dogs, the latter considered venomous due to its ‘poisonous’ saliva, and to a lesser extent, scorpions and spiders. In general the bites of non-venomous animals received scant attention. Unlike modern taxonomical categories, medieval categories for animals were usually connected to the movement or the locale of the animal: flying animals, animals in water, land animals (which mainly covered quadrupeds), and crawling animals. It is in the latter category that snakes were located, along with lizards. PMID:25729094

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

PubMed

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

2015-03-01

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

Vitamin D Deficiency Exacerbates Experimental Stroke Injury and Dysregulates Ischemia-Induced Inflammation in Adult Rats

PubMed Central

Balden, Robyn; Selvamani, Amutha

2012-01-01

Vitamin D deficiency (VDD) is widespread and considered a risk factor for cardiovascular disease and stroke. Low vitamin D levels are predictive for stroke and more fatal strokes in humans, whereas vitamin D supplements are associated with decreased risk of all-cause mortality. Because VDD occurs with other comorbid conditions that are also independent risk factors for stroke, this study examined the specific effect of VDD on stroke severity in rats. Adult female rats were fed control or VDD diet for 8 wk and were subject to middle cerebral artery occlusion thereafter. The VDD diet reduced circulating vitamin D levels to one fifth (22%) of that observed in rats fed control chow. Cortical and striatal infarct volumes in animals fed VDD diet were significantly larger, and sensorimotor behavioral testing indicated that VDD animals had more severe poststroke behavioral impairment than controls. VDD animals were also found to have significantly lower levels of the neuroprotective hormone IGF-I in plasma and the ischemic hemisphere. Cytokine analysis indicated that VDD significantly reduced IL-1α, IL-1β, IL-2, IL-4, IFN-γ, and IL-10 expression in ischemic brain tissue. However, ischemia-induced IL-6 up-regulation was significantly higher in VDD animals. In a separate experiment, the therapeutic potential of acute vitamin D treatments was evaluated, where animals received vitamin D injections 4 h after stroke and every 24 h thereafter. Acute vitamin D treatment did not improve infarct volume or behavioral performance. Our data indicate that VDD exacerbates stroke severity, involving both a dysregulation of the inflammatory response as well as suppression of known neuroprotectants such as IGF-I. PMID:22408173

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

PubMed

Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

2009-06-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Simvastatin Exposure and Rotator Cuff Repair in a Rat Model.

PubMed

Deren, Matthew E; Ehteshami, John R; Dines, Joshua S; Drakos, Mark C; Behrens, Steve B; Doty, Stephen; Coleman, Struan H

2017-03-01

Simvastatin is a common medication prescribed for hypercholesterolemia that accelerates local bone formation. It is unclear whether simvastatin can accelerate healing at the tendon-bone interface after rotator cuff repair. This study was conducted to investigate whether local and systemic administration of simvastatin increased tendon-bone healing of the rotator cuff as detected by maximum load to failure in a controlled animal-based model. Supraspinatus tendon repair was performed on 120 Sprague-Dawley rats. Sixty rats had a polylactic acid membrane overlying the repair site. Of these, 30 contained simvastatin and 30 did not contain medication. Sixty rats underwent repair without a polylactic acid membrane. Of these, 30 received oral simvastatin (25 mg/kg/d) and 30 received a regular diet. At 4 weeks, 5 rats from each group were killed for histologic analysis. At 8 weeks, 5 rats from each group were killed for histologic analysis and the remaining 20 rats were killed for biomechanical analysis. One rat that received oral simvastatin died of muscle necrosis. Average maximum load to failure was 35.2±6.2 N for those receiving oral simvastatin, 36.8±9.0 N for oral control subjects, 39.5±12.8 N for those receiving local simvastatin, and 39.1±9.3 N for control subjects with a polylactic acid membrane. No statistically significant differences were found between any of the 4 groups (P>.05). Qualitative histologic findings showed that all groups showed increased collagen formation and organization at 8 weeks compared with 4 weeks, with no differences between the 4 groups at each time point. The use of systemic and local simvastatin offered no benefit over control groups. [Orthopedics. 2017; 40(2):e288-e292.]. Copyright 2016, SLACK Incorporated.

Diet composition modifies the toxicity of repeated soman exposure in rats.

PubMed

Langston, Jeffrey L; Myers, Todd M

2011-12-01

It was previously demonstrated that diet potently modulates the toxic effects of an acute lethal dose of the nerve agent soman. The current investigation was undertaken to examine the influence of diet on the cumulative toxicity of repeated soman administration. Rats were fed one of four distinct diets (standard, choline-enriched, glucose-enriched, or ketogenic) for four weeks prior to and throughout a repeated soman dosing and recovery regimen. Each diet group included animals exposed to an equivalent volume of saline that served as negative controls. In exposure Week 1, animals received three consecutive daily doses of 0.4 LD(50) soman. In exposure Week 2, animals received four consecutive daily doses of 0.5 LD(50) soman. In exposure Week 3, animals received five consecutive daily doses of 0.5 LD(50) soman. Week 4 constituted a post-exposure recovery evaluation. Throughout the experiment, behavioral function was assessed by a discriminated avoidance test that required intact sensory and motor function. Survival and body weight changes were recorded daily. Differences in toxicity as a function of diet composition became apparent during the first week. Specifically, rats fed the glucose-enriched diet showed pronounced intoxication during Week 1, resulting in imperfect survival, weight loss, and deteriorated avoidance performance relative to all other groups. All rats fed the glucose-enriched diet died by the end of exposure Week 2. In contrast, only 10% of animals fed the standard diet died by the end of Week 2. Also in Week 2, weight loss and disrupted avoidance performance were apparent for all groups except for those fed the ketogenic diet. This differential effect of diet composition became even more striking in Week 3 when survival in the standard and choline diet groups approximated 50%, whereas survival equaled 90% in the ketogenic diet group. Avoidance performance and weight loss measures corroborated the differential toxicity observed across diet groups. Upon cessation of soman exposure during the final week, recovery of weight and avoidance performance in survivors was comparable across diet groups. These results systematically replicate previous findings demonstrating that diet composition exacerbates or attenuates toxicity in rodents exposed acutely to organophosphorus compounds. Published by Elsevier B.V.

[Evaluation of rabies-suspected bites in Giresun, eastern Black-Sea region, Turkey].

PubMed

Torun, Mustafa

2010-10-01

This study was conducted to retrospectively evaluate a total of 4390 cases (1712 female, mean age: 25 years old; 2678 male, mean age: 35 years old) admitted to the rabies vaccine center of Giresun State Hospital, a province located at eastern Black-Sea region of Turkey, with the history of animal bite between the years of 2005-2009. It was determined that 74.5% of the cases were bitten by dogs, 22% by cats and 3.5% by wild animals and others. The most frequently bitten area was the lower extremities (n= 2678, 61%) (buttocks, legs and foot in order of decreasing frequency), followed by upper extremities (n= 1200, 27%) (hands, arms, head and neck area) and other areas (n=512, 11.6%) (back, abdomen, groin). According to the "Rabies Protection and Control Guidelines" of the Turkish Ministry of Health, 3210 cases (98.8%) were only vaccinated against rabies and 38 cases (1.2%) were both vaccinated and applied rabies antiserum according to the risk factors related to the suspected bite. Ten days follow-up of the suspected animal was recommended to 1142 (26%) cases and since no death were detected among these animals, no vaccination were applied. In conclusion, since this specific area with mountains and forests is suitable for the inhabitance of reservoir animals, risk groups such as workers in the forest should receive pre-exposure prophylaxis and specific precautions should be undertaken for the vaccination and/or care of dogs for effective rabies control.