Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

PubMed Central

2012-01-01

Background This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats. Methods Wistar rats were used and divided into six groups: sedentary alloxan (SA), sedentary control (SC), continuous trained alloxan (CA), intermittent trained alloxan (IA), continuous trained control (CC) and intermittent trained control (IC). Alloxan (250 mg/kg body weight) was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. Results At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. Conclusion It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals. PMID:22309804

Circumvallate papilla of dog following suture of the hypoglossal and glossopharyngeal nerves.

PubMed

State, F A

1977-01-01

20 adult dogs were classified into five groups; in two animals of each group hypoglossa-glossopharyngeal suturing was done. In the other two animals glossopharyngeal nerve transection with concomitant central segment avulsion was done and these two animals were used as controls. The animals of the five groups were sacrified at 4-week intervals starting by the first group on the 4th post-operative week and ending by the fifth group on the 20th week; the circumvallate papillae were studied. On the 4th week following either operative procedure, few taste buds persisted on the circumvallate papillae. Invasion of the papillae by regenerating hypoglossal fibres from the 8th week onwards was not followed by any appreciable increase in the number of taste buds. The difference in number of taste buds between hypoglossal-glossopharyngeal suture and glossopharyngeal avulsion procedures was not statistically significant. from the 8th weeks following cross-innervation the reaction for acetylcholinesterase was more intense than in denervated papillae which showed a persistent weakly positive reaction up to the 20th post-operative week.

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.

Effects of random food deprivation and refeeding on energy metabolism, behavior and hypothalamic neuropeptide expression in Apodemus chevrieri.

PubMed

Wan-Long, Zhu; Zheng-Kun, Wang

2016-11-01

Maintaining adaptive control of behavior and physiology is the main strategy used by animals in responding to changes of food resources. To investigate the effects of random food deprivation (FD) and refeeding on energy metabolism and behavior in Apodemus chevrieri, we acclimated adult males to FD for 4weeks, then refed them ad libitum for 4weeks (FD-Re group). During the period of FD, animals were fed ad libitum for 4 randomly assigned days each week, and deprived of food the other 3days. A control group was fed ad libitum for 8weeks. At 4 and 8weeks we measured body mass, thermogenesis, serum leptin levels, body composition, gastrointestinal tract morphology, behavior and hypothalamic neuropeptide expression. At 4weeks, food intake, gastrointestinal mass, neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expressions increased and thermogenesis, leptin levels, pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) expressions decreased in FD compared with controls. FD also showed more resting behavior and less activity than the controls on ad libitum day. There were no differences between FD-Re and controls at 8weeks, indicating significant plasticity. These results suggested that animals can compensate for unpredictable reduction in food availability by increasing food intake and reducing energy expended through thermogenesis and activity. Leptin levels, NPY, AgRP, POMC, and CART mRNA levels may also regulate energy metabolism. Significant plasticity in energy metabolism and behavior was shown by A. chevrieri over a short timescale, allowing them to adapt to food shortages in nutritionally unpredictable environments. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-01-01

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

The architecture of the avian retina following exposure to chronic 2 G

NASA Technical Reports Server (NTRS)

Orlando, R. G.; Negulesco, J. A.

1980-01-01

Rhode Island Red female chicks at 2 weeks posthatch were subjected, for 7 d, to either earth gravity of 1 G or a 2-G hypergravity environment by chronic whole-body centrifugation. Animals were sacrificed at 3 weeks posthatch and the eyes were enucleated, fixed in 10% BNF, doubly embedded, sectioned at 7-8 microns and routinely processed with H & E for histological examination. Compared to normogravity controls, animal exposure for 1 week to the chronic effects of 2-G resulted in a significantly decreased mean width of the photoreceptor, inner nuclear, and inner plexiform retinal layers. The outer nuclear, outer plexiform, and ganglion cell layers of the retina appeared minimally affected by the hypergravity state since the mean width of these layers showed no noticeable differences from earth gravity control animals. The present anatomic findings suggest a reduction in the detection of motion or rapid changes in illumination by the avian retina when the animal is exposed at a 2-G environment.

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.

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

PubMed

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

2014-01-17

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

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

PubMed

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

2014-04-01

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

Influence of age on the effectiveness of PCV2 vaccination in piglets with high levels of maternally derived antibodies.

PubMed

Haake, Michael; Palzer, Andreas; Rist, Beate; Weissenbacher-Lang, Christiane; Fachinger, Vicky; Eggen, Alex; Ritzmann, Mathias; Eddicks, Matthias

2014-01-31

Two field studies were conducted to investigate the influence of age on the efficacy of vaccination against Porcine Circovirus Diseases (PCVD) in animals with high levels of maternally derived antibodies (MDA). A total of 416 piglets (Study 1) and 600 piglets (Study 2) were randomly allocated to one of three groups. Two groups in each study received a single dose of a PCV2 subunit vaccine, one group at 1 week old and the other at 3 weeks of age. The third group was left untreated. Animals vaccinated at 3 weeks of age showed a significantly higher average daily weight gain and significantly reduced viraemia following PCV2 infection than the respective control groups. This difference was not observed in pigs vaccinated at 1 week of age. Furthermore, only animals vaccinated at 3 weeks of age showed an increased serological response and a higher frequency of IgM-positive animals compared with controls. The data indicated that PCV2 vaccination in the presence of high MDA levels is efficacious when used in 3-week old but not in 1-week old pigs. As the range of MDA titres of pigs vaccinated at both 1 and 3 weeks of age were comparable, the data suggest that PCV2 vaccine efficacy was independent of the level of MDA. It appears that other age-related factors affecting the active and passive transfer of immunity may perhaps have interfered with the efficacy of the vaccine in 1-week old piglets. These findings have implications for future PCV2 vaccine testing and administration strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

(+/-)-3,4-Methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: a comparison of single vs once per week treatment for 5 weeks.

PubMed

Skelton, Matthew R; Able, Jessica A; Grace, Curtis E; Herring, Nicole R; Schaefer, Tori L; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

2008-12-01

3,4-Methlylenedioxymethamphetamine (MDMA) administration (4 x 15 mg/kg) on a single day has been shown to cause path integration deficits in rats. While most animal experiments focus on single binge-type models of MDMA use, many MDMA users take the drug on a recurring basis. The purpose of this study was to compare the effects of repeated single-day treatments with MDMA (4 x 15 mg/kg) once weekly for 5 weeks to animals that only received MDMA on week 5 and saline on weeks 1-4. In animals treated with MDMA for 5 weeks, there was an increase in time spent in the open area of the elevated zero maze suggesting a decrease in anxiety or increase in impulsivity compared to the animals given MDMA for 1 week and saline treated controls. Regardless of dosing regimen, MDMA treatment produced path integration deficits as evidenced by an increase in latency to find the goal in the Cincinnati water maze. Animals treated with MDMA also showed a transient hypoactivity that was not present when the animals were re-tested at the end of cognitive testing. In addition, both MDMA-treated groups showed comparable hyperactive responses to a later methamphetamine challenge. No differences were observed in spatial learning in the Morris water maze during acquisition or reversal but MDMA-related deficits were seen on reduced platform-size trials. Taken together, the data show that a single-day regimen of MDMA induces deficits similar to that of multiple weekly treatments.

An animal model (guinea pig) of ocular siderosis: histopathology, pharmacology, and electrophysiology.

PubMed

Mumcuoglu, Tarkan; Ozge, Gokhan; Soykut, Bugra; Erdem, Onur; Gunal, Armagan; Acikel, Cengizhan

2015-03-01

Ocular siderosis is a rare sight-threatening complication that occurs after a penetrating ocular injury by an iron-containing foreign body. The purposes of this study were to (i) investigate the histopathology, electrophysiology and iron levels/accumulation in ocular siderosis using an animal (Guinea pig) model and (ii) determine the appropriate timing for follow-up foreign body-removal surgery. Thirty guinea pigs were divided into five groups (n = 6 animals/group). On day-1, an iron body was inserted into the vitreous of the right eye of all animals; the left eyes were left undisturbed and were used as controls. At the end of each week during the 5-week study period, electroretinography (ERG) was performed on all animals in one of the five groups. Each animal in that group was sacrificed, after which both eyes were enucleated for histopathological and pharmacological evaluation of intraocular iron. Accumulated iron levels of study eyes were significantly higher than those of control eyes (135.13 and 13.55 μg/g, respectively, p < 0.01). In addition, there was a significant decrease in electrophysiological responses of study eyes. During the first week, iron levels were higher in study eyes than control eyes, but neither histological iron accumulation nor decreased electrophysiological responses could be detected. By the end of the second week, increased iron accumulation was observed histologically in intraocular tissues, along with signs of retinal toxicity, as verified by decreased electrophysiological responses. The present study indicates that the 14th day after a penetrating eye injury by an iron-containing intraocular foreign body represents a clinically critical threshold, after which structural damage to and functional alterations in ocular tissues occur.

Angiotensinogen concentration in the cerebrospinal fluid in different experimental conditions in the rat.

PubMed

Ruiz, P; Basso, N; Grinspon, D; Mangiarua, E; Cannata, M A

1983-01-01

Angiotensinogen is the most important component of the renin-angiotensin system present in the cerebrospinal fluid (CSF) of the rat. Its physiological significance as well as its origin have not been clearly elucidated. In this experiment we have examined plasma renin activity (PRA) and plasma and CSF angiotensinogen concentration under the following experimental conditions in male rats of the Wistar strain: 1) adrenalectomy (Adx) 4 days prior to sample collection; controls were sham Adx animals; 2) nephrectomy (Nx) 48 hours before blood and CSF collection; controls were sham Nx rats; 3) DOC-salt treatment (Cortexon depot, 50 mg/kg.s.c. twice a week) plus saline to drink was given during 4 weeks; controls were intact rats; 4) DOC-salt plus captopril: captopril (100 mg/kg/day) in the drinking fluid was added to the treatment of experimental and control animals of Group 3; 5) two-kidney, two clip hypertension: silver clips placed in both renal arteries 8 weeks before samples collection; control: sham-operated rats; 6) water deprivation: rats deprived of water for 5 days; controls: intact rats; 7) peripheral sympathectomy: 6-hydroxydopamine (6-HODA) injected s.c. from birth until 16 weeks of age, adrenodemedullectomy and adrenal denervation performed at 8 weeks; controls were vehicle-injected animals. Determination of angiotensinogen concentration in plasma and CSF was accomplished by incubation of the samples with excess hog renin. The angiotensin I released as well as PRA were evaluated using an specific radioimmunoassay technique. PRA was significantly increased by Adx, captopril treatment, and water deprivation, and was almost suppressed by Nx, DOC-salt, and DOC-salt plus captopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Embolization of arterial gastric supply in obesity (EMBARGO): an endovascular approach in the management of morbid obesity. proof of the concept in the porcine model.

PubMed

Diana, Michele; Pop, Raoul; Beaujeux, Rémy; Dallemagne, Bernard; Halvax, Peter; Schlagowski, Isabel; Liu, Yu-Yin; Diemunsch, Pierre; Geny, Bernard; Lindner, Veronique; Marescaux, Jacques

2015-03-01

Embolization of the left gastric artery (LGA) reduces circulating levels of ghrelin, but might prevent from further obesity surgery, particularly sleeve gastrectomy (SG), since the gastroesophageal junction (GEJ), depending on LGA, would be devascularized. Our aim was to evaluate, in an experimental animal study, an endovascular approach targeting arteries of the gastroepiploic arcade aiming to modulate ghrelin levels and to generate an increased vascular supply of the GEJ to reduce the risks of staple-line leaks after SG. Seven pigs underwent embolization of both left and right gastroepiploic arteries (LGEA and RGEA) using 500-700-μ microspheres (embolization of arterial gastric supply in obesity (EMBARGO)-alpha). A SG was performed in six pigs 3 weeks after EMBARGO-alpha and on eight controls. Capillary lactates were measured at the cardia and pylorus. Five pigs underwent coiling of RGEA and embolization of LGEA using both coils and 100-300-μ microspheres (EMBARGO-beta). Ghrelin levels were assessed before and once per week after both EMBARGOs. Control celiac trunk angiography was performed at 3 weeks (alpha) and 4 weeks (beta). No significant ghrelin reduction was obtained with EMBARGO-alpha at 3 weeks when compared to baseline. Significant ghrelin reduction was found 3 weeks (p = 0.0363) and 4 weeks (p = 0.025) after EMBARGO-beta. Post-EMBARGO-alpha animals presented a significantly lower increase in cardia lactates when compared to controls after SG. Control angiography showed a significantly increased fundic vascular network in 5/6 animals after EMBARGO-alpha and in 5/5 after EMBARGO-beta. EMBARGO is effective to decrease ghrelin production and can enhance the vascular supply of the GEJ, preparing the vascular background for a SG.

Triamcinolone Acetonide Decreases Outflow Facility in C57BL/6 Mouse Eyes

PubMed Central

Kumar, Sandeep; Shah, Shaily; Deutsch, Emily Rose; Tang, Hai Michael; Danias, John

2013-01-01

Purpose. To determine the effect of triamcinolone acetonide (TA) on outflow facility in mice. Methods. Animals received 20 μL of TA (40 mg/mL) suspension subconjunctivally either bilaterally or unilaterally and were euthanized after either 1 week or 3 weeks. Before mice were killed, IOP was measured with a rebound tonometer. Outflow facility was determined using simultaneous pressure and flow measurements. Another set of animals received bilateral injection of anecortave acetate (AA) with or without bilateral TA injection and their outflow facility was also determined. Myocilin expression was investigated in a subset of eyes using quantitative PCR (qPCR). Results. Outflow facility of eyes in animals receiving bilateral TA injection (TABL) and TA-treated eyes of animals receiving unilateral injection (TAUL) was significantly decreased compared to naïve control eyes (Cnaive) after 1 week and 3 weeks of TA treatment (ANOVA P < 0.01, P < 0.001, respectively). Eyes treated with AA (with or without TA) had higher outflow facility than animals treated with TA (P < 0.05). IOP data did not show any significant difference between groups. qPCR analysis revealed significant decrease in myocilin expression in eyes receiving AA compared to naïve control and TA-treated eyes (ANOVA P < 0.001). Conclusions. Steroid treatment significantly decreases outflow facility in C57BL/6 mice despite having small effect on IOP. This animal model can be useful for studying the pathogenesis of steroid-induced glaucoma. PMID:23322580

Ghrelin Suppression and Fat Loss after Left Gastric Artery Embolization in Canine Model

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

Bawudun, Dilmurat; Xing Yan; Liu Wenya, E-mail: wenyaliu2002@hotmail.com

Purpose: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. Methods: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A{sub 5} hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8more » weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. Results: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). Conclusion: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.« less

Ghrelin suppression and fat loss after left gastric artery embolization in canine model.

PubMed

Bawudun, Dilmurat; Xing, Yan; Liu, Wen-Ya; Huang, Yu-Jie; Ren, Wei-Xin; Ma, Mei; Xu, Xiao-Dong; Teng, Gao-Jun

2012-12-01

To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A(5) hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure.

PubMed

Ahmmed, G U; Dong, P H; Song, G; Ball, N A; Xu, Y; Walsh, R A; Chiamvimonvat, N

2000-03-17

Ventricular arrhythmias are common in both cardiac hypertrophy and failure; cardiac failure in particular is associated with a significant increase in the risk of sudden cardiac death. We studied the electrophysiologic changes in a guinea pig model with aortic banding resulting in cardiac hypertrophy at 4 weeks and progressing to cardiac failure at 8 weeks using whole-cell patch-clamp and biochemical techniques. Action potential durations (APDs) were significantly prolonged in banded animals at 4 and 8 weeks compared with age-matched sham-operated animals. APDs at 50% and 90% repolarization (APD(50) and APD(90) in ms) were the following: 4 week, banded, 208+/-51 and 248+/-49 (n = 15); 4 week, sham, 189+/-68 and 213+/-69 (n = 16); 8 week, banded, 197+/-40 and 226+/-40 (n = 21); and 8 week, sham, 156+/-42 and 189+/-45 (n = 22), respectively; P<0.05 comparing banded versus sham-operated animals. We observed no significant differences in the K(+) currents between the 2 groups of animals at 4 and 8 weeks. However, banded animals exhibited a significant increase in Na(+) and Na(+)-Ca(2+) exchange current densities compared with controls. Furthermore, we have found a significant attenuation in the Ca(2+)-dependent inactivation of the L-type Ca(2+) current in the banded compared with sham-operated animals, likely as a result of the significant downregulation of the sarcoplasmic reticulum Ca(2+) ATPase, which has been documented previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and support the notion that there is close interaction between Ca(2+) handling and action potential profile.

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

[Establishment of animal model of temporomandibular joint synovitis and its histological investigation].

PubMed

Chen, Cai-Yun; Ding, Yin; Liu, Ya-Jing; Zhang, Ya-Bo

2010-02-01

To establish a stable animal model of temporomandibular joint (TMJ) synovitis. Sixteen 6-week-old male SD rats were classified into four groups, control group, occlusal dimension increase group, masseter resection group, occlusal dimension increase group and masseter resection group. The rats in the occlusal dimension increase group were adhered composite resin to their maxillary molars in order to increase the occlusal vertical dimension when they were 9-week-old. The rats in the masseter resection group were cut off their bilateral masseter muscles when they were 6-week-old. In the occlusal dimension increase group and masseter resection group, rats' bilateral masseter muscles were resected and occlusal vertical dimension was increased. All rats were sacrificed at their 10 weeks old. TMJ samples were prepared for histology to evaluate the animal model. The control group showed non-inflammatory changes. The occlusal dimension increase group and the masseter resection group showed vascular dilation and synovial lining proliferation, but there were no statistically significant differences between the two groups (P > 0.05). Compared to the two disposed groups, the occlusal dimension increase group and masseter resection group showed significant inflammatory changes (P < 0.05), including synovial lining proliferation, vascular dilation and fibrin deposit. The animal model of TMJ synovitis created in the present investigation could simulate the real pathological features of synovitis in vivo, and this animal model showed the obvious merits of high stability and reproduction.

Influence of UVB exposure on the vitamin D status and calcium homoeostasis of growing sheep and goats.

PubMed

Kovács, S; Wilkens, M R; Liesegang, A

2015-04-01

The purpose of this study was to investigate the influence of exposure to ultraviolet radiation (UVB) on vitamin D status, intestinal calcium absorption and bone metabolism in growing sheep and goats. The hypothesis was that growing sheep and goats are able to synthesise vitamin D within their skin as a result of UVB exposure and that respective consequences for their vitamin D blood levels and the associated parameters can be shown. Fourteen 18-week-old lambs and goat kids were kept in an UVB-free environment and randomly assigned to two groups. One group was daily exposed to UVB (300 watt) for 12 weeks, and the other served as a control group. Except for the exposure to UVB, all animals were kept under the same conditions and fed according to their requirements. Before the start of the experiment and every second week, blood samples were taken. Also the left metatarsus of each animal was analysed by quantitative computer tomography to test for bone mineral status before the start, in week 7 and at the end of the experiment. After 12 weeks, the animals were slaughtered and samples were taken from skin, gastrointestinal tract and kidney for further analyses. In this study, exposure to UVB led to increased serum 1,25-dihydroxyvitamin D (1,25VitD) levels in goat kids, whereas in lambs, serum 25-hydroxyvitamin D (25VitD) levels were increased. In both species UVB-exposed animals showed lower 7-dehydrocholesterol (7DHC) values in skin than their respective control groups. These results indicate that growing goat kids and lambs are able to synthesise vitamin D in the skin when being exposed to UVB. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

PubMed Central

Kertész, Attila; Bombicz, Mariann; Priksz, Daniel; Balla, Jozsef; Balla, Gyorgy; Gesztelyi, Rudolf; Varga, Balazs; Haines, David D.; Tosaki, Arpad; Juhasz, Bela

2013-01-01

The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls. PMID:24048247

Effect of the probiotic Enterococcus faecium SF68 on presence of diarrhea in cats and dogs housed in an animal shelter.

PubMed

Bybee, S N; Scorza, A V; Lappin, M R

2011-01-01

Beneficial effects of probiotics have never been analyzed in an animal shelter. Dogs and cats housed in an animal shelter and administered a probiotic are less likely to have diarrhea of ≥2 days duration than untreated controls. Two hundred and seventeen cats and 182 dogs. Double blinded and placebo controlled. Shelter dogs and cats were housed in 2 separate rooms for each species. For 4 weeks, animals in 1 room for each species was fed Enterococcus faecium SF68 while animals in the other room were fed a placebo. After a 1-week washout period, the treatments by room were switched and the study continued an additional 4 weeks. A standardized fecal score system was applied to feces from each animal every day by a blinded individual. Feces of animals with and without diarrhea were evaluated for enteric parasites. Data were analyzed by a generalized linear mixed model using a binomial distribution with treatment being a fixed effect and the room being a random effect. The percentage of cats with diarrhea ≥2 days was significantly lower (P = .0297) in the probiotic group (7.4%) when compared with the placebo group (20.7%). Statistical differences between groups of dogs were not detected but diarrhea was uncommon in both groups of dogs during the study. Cats fed SF68 had fewer episodes of diarrhea of ≥2 days when compared with controls suggests the probiotic may have beneficial effects on the gastrointestinal tract. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Chronological production of thioacetamide-induced cirrhosis in the rat with no mortality.

PubMed

Norasingha, Arthit; Pradidarcheep, Wisuit; Chayaburakul, Kanokporn

2012-01-01

Cirrhotic animal models are useful in studying complications of chronic liver disease. The authors chronologically investigated the effect of thioacetamide (TAA), administered intraperitoneally and adapted individually to weight changes, focusing on the optimal moment to obtain typical features of cirrhosis. Male Wistar Rats,150-200 g, were intoxicated three times per week with TAA of 200 mg/kg for 4, 8, 12 or 16 weeks (n = 8 per group), respectively and compared with age-matched controls (n = 4 per group). The individual body weight and liver function test were also measured in each group. Liver samples from each group were histologically stained with Sirius red in order to identify the degree of liver fibrosis. Rats intoxicated for 4, 8, 12 or 16 weeks had no mortality and histologically showed hepatitis and advanced fibrosis. At 12 and 16 weeks, all animals showed macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. The weight of the treated groups at different time points was significantly lower than the controls. Routine liver function tests between cirrhotic and control rats showed significantly higher only in alanine transaminase (ALT) and aspartate aminotransferase (AST) at 8 and 12 weeks. However in the cirrhotic rats at 16 weeks, the ALT and AST were much lower than that at 8 and 12 weeks but did not show any difference from the controls. Thioacetamide, adapted to individual weight changes, leads to a model of cirrhosis in the rat at 12 and 16 weeks with zero mortality.

Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae.

PubMed

Checa, Sara; Hesse, Bernhard; Roschger, Paul; Aido, Marta; Duda, Georg N; Raum, Kay; Willie, Bettina M

2015-07-01

Although it is well known that the bone adapts to changes in the mechanical environment by forming and resorbing the bone matrix, little is known about the influence of mechanical loading on tissue material properties of the pre-existing and newly formed bone. In this study, we analyzed the newly formed and pre-existing tissue after two weeks of controlled in vivo axial compressive loading in tibia of young (10 week-old) and adult (26 week-old) female mice and compared to the control contralateral limb, by means of scanning acoustic microscopy. Additionally, we used quantitative backscattered electron imaging to determine the bone mineral density distribution within the newly formed and pre-existing bone of young mice. No significant differences were found in tissue stiffness or mineral density in the pre-existing bone tissue as a result of external loading. In the endosteal region, 10 and 26 week loaded animals showed a 9% reduction in bone tissue stiffness compared to control animals. An increase of 200% in the mineral apposition rate in this region was observed in both age groups. In the periosteal region, the reduction in bone tissue stiffness and the increase in bone mineral apposition rate as a result of loading were two times higher in the 10 compared to the 26 week old animals. These data suggest that, during growth and skeletal maturation, the response of bone to mechanical loading is a deposition of new bone matrix, where the tissue amount but not its mineral or elastic properties are influenced by animal age. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability.

PubMed

Packer, Jonathan D; Varthi, Arya G; Zhu, David S; Javier, Frances G; Young, Jason D; Garver, Jennie V; Henry, Havalee; Tommasini, Steven M; Blaine, Theodore A

2018-02-01

Failure of glenoid labrum and capsular healing after glenohumeral dislocation can lead to persistent shoulder instability. The purpose of this study was to determine the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the healing glenoid labrum and capsule after glenohumeral dislocation in a rat model. Sixty-six rats had surgically induced anterior-inferior labral tears and anterior glenohumeral dislocation. Postoperatively, the animals were assigned to either normal (n = 32) or ibuprofen drinking water (n = 31). Animals were euthanized at 2 and 4 weeks postoperatively for biomechanical testing and histologic analysis. The maximum load increased from 2 to 4 weeks after injury in the NSAID groups but not in the control groups. At 2 weeks, the maximum load was lower in the NSAID group compared with the control group. In a matched comparison between injured and uninjured limbs, the maximum load was significantly decreased in the injured limb of the 2-week NSAID group. At 4 weeks, the NSAID group had decreased stiffness compared with the 4-week control group. In a new rat model of glenohumeral instability, the postinjury administration of ibuprofen resulted in decreased capsulolabral healing. A matched pair analysis of injured to uninjured limbs supported the findings of impaired healing in the NSAID-treated animals. These findings demonstrate that the use of NSAIDs after glenohumeral dislocation may impair capsulolabral healing and should be limited or avoided to optimize glenohumeral stability. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. 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.

Experimental palatal candidosis and saliva flow in monkeys.

PubMed

Olsen, I; Haanaes, H R

1977-01-01

Maxillary acrylic plates, inoculated with Candida albicans, were inserted for 3 weeks in 10 monkeys (Cercopithecus aethiops) (Series I), and reinserted in five of the animals 8 weeks after removal (Series II). To suppress saliva flow oxyphencyclimine was injected intramuscularly (0.125 mg/kg) thrice daily for 3 weeks in six monkeys of Series I, while four controls received no drug. In Series II the oxyphencyclimine dose was doubled in three animals, and two controls were sham-treated with sodium chloride. Mean saliva flow was reduced to 58% after 1 week and to 63% after 3 weeks with the low dose of oxyphencyclimine. The values with the high dose were 56% and 64%, respectively. After 1 week thrush had developed beneath the plates of all monkeys. The patches were more extensive and regressed slower with oxyphencyclimine. Enlarged lesions were seen with the double dose. In Series I intraepithelial invasion by hyphae was detected more frequently and longer after inoculation in the oxyphencyclimine group. Such invasion was not found in biopsies from Series II. It is likely that saliva offers some protection against yeasts colonizing the fitting size of a denture.

Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.

PubMed

Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V; Schultz, David J; Gupta, Ramesh C

2017-02-16

Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% ( w / w ) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control group. At the end of the study (25 weeks), the tumor incidence was 96% in the control group compared with only 70% in the caraway group. A significant reduction in tumor volume (661 ± 123 vs. 313 ± 81 mm³) and tumor multiplicity (4.2 ± 0.4 vs. 2.5 ± 0.5 tumors/animal) was also observed in the caraway group compared with the control group. Together, our data show dietary caraway can significantly delay and prevent the hormonal mammary tumorigenesis by modulating different cellular and molecular targets.

Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

PubMed Central

Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V.; Schultz, David J.; Gupta, Ramesh C.

2017-01-01

Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control group. At the end of the study (25 weeks), the tumor incidence was 96% in the control group compared with only 70% in the caraway group. A significant reduction in tumor volume (661 ± 123 vs. 313 ± 81 mm3) and tumor multiplicity (4.2 ± 0.4 vs. 2.5 ± 0.5 tumors/animal) was also observed in the caraway group compared with the control group. Together, our data show dietary caraway can significantly delay and prevent the hormonal mammary tumorigenesis by modulating different cellular and molecular targets. PMID:28212313

Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of Rauwolfia vomitoria foilage and Citrus aurantium fruit.

PubMed

Campbell, Joan I A; Mortensen, Alicja; Mølgaard, Per

2006-04-06

The toxicity and anti-diabetic properties of an aqueous plant extract made by boiling Rauwolfia vomitoria foilage and Citrus aurantium fruits were evaluated in mice. A single dosage corresponding to 70x the human-daily-dose was non-toxic when administered to 6-week-old NMRI lean mice or 6- or 11-week-old C57BL/6J lean mice. Daily treatment of 11-week-old C57BL/KsBom-db (db/db) genetic diabetic mice with a dose corresponding to 10x human-daily-dose for 6 weeks facilitated a significant weight loss as compared to the untreated controls. During treatment, the db/db mice were maintained on the carbohydrate-deficient Altromin C1009 diet. Although the food intake in the treated mice was not statistically significant from that in the controls, the treated animals had significantly higher serum triglyceride contents, suggesting that the treatment induced lipid mobilization from internal stores. Moreover, the fatty acid profile of the eyes from the treated animals showed a significant reduction in total fatty acid content accompanied by a 33% reduction in estimated Stearoyl-CoA desaturase activity (p = 0.039) as compared with controls. The fatty acid mobilization and a protection of the brittle C57BL/KsBom-db pancreas were observed 5 weeks after cessation of treatment when the treated animals were maintained on the poorer Altromin C1009 diet.

Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

PubMed

Holfeld, Johannes; Zimpfer, Daniel; Albrecht-Schgoer, Karin; Stojadinovic, Alexander; Paulus, Patrick; Dumfarth, Julia; Thomas, Anita; Lobenwein, Daniela; Tepeköylü, Can; Rosenhek, Raphael; Schaden, Wolfgang; Kirchmair, Rudolf; Aharinejad, Seyedhossein; Grimm, Michael

2016-12-01

Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm 2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p < 0.001) and control (41 ± 4%, p = 0.012) groups. LVEF markedly improved in shock-wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed

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

2016-01-01

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

Prime-boost vaccination using DNA and whole inactivated virus vaccines provides limited protection against virulent feline immunodeficiency virus.

PubMed

Dunham, Stephen P; Bruce, Jennifer; Klein, Dieter; Flynn, J Norman; Golder, Matthew C; MacDonald, Susan; Jarrett, Oswald; Neil, James C

2006-11-30

Protection against feline immunodeficiency virus (FIV) has been achieved using a variety of vaccines notably whole inactivated virus (WIV) and DNA. However protection against more virulent isolates, typical of those encountered in natural infections, has been difficult to achieve. In an attempt to improve protection against virulent FIV(GL8), we combined both DNA and WIV vaccines in a "prime-boost" approach. Thirty cats were divided into four groups receiving vaccinations and one unvaccinated control group. Following viral challenge, two vaccinated animals, one receiving DNA alone and one the prime-boost vaccine remained free of viraemia, whilst all controls became viraemic. Animals vaccinated with WIV showed apparent early enhancement of infection at 2 weeks post challenge (pc) with higher plasma viral RNA loads than control animals or cats immunised with DNA alone. Despite this, animals vaccinated with WIV or DNA alone showed significantly lower proviral loads in peripheral blood mononuclear cells and mesenteric lymph node cells, whilst those receiving the DNA-WIV prime-boost vaccine showed significantly lower proviral loads in PBMC, than control animals, at 35 weeks pc. Therefore both DNA and WIV vaccines conferred limited protection against viral challenge but the combination of WIV and DNA in a prime-boost approach appeared to offer no significant advantage over either vaccine alone.

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

PubMed Central

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

2002-01-01

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

Space flight affects magnocellular supraoptic neurons of young prepuberal rats: transient and permanent effects

NASA Technical Reports Server (NTRS)

Garcia-Ovejero, D.; Trejo, J. L.; Ciriza, I.; Walton, K. D.; Garcia-Segura, L. M.

2001-01-01

Effects of microgravity on postural control and volume of extracellular fluids as well as stress associated with space flight may affect the function of hypothalamic neurosecretory neurons. Since environmental modifications in young animals may result in permanent alterations in neuroendocrine function, the present study was designed to determine the effect of a space flight on oxytocinergic and vasopressinergic magnocellular hypothalamic neurons of prepuberal rats. Fifteen-day-old Sprague-Dawley female rats were flown aboard the Space Shuttle Columbia (STS-90, Neurolab mission, experiment 150) for 16 days. Age-matched litters remained on the ground in cages similar to those of the flight animals. Six animals from each group were killed on the day of landing and eight animals from each group were maintained under standard vivarium conditions and killed 18 weeks after landing. Several signs of enhanced transcriptional and biosynthetic activity were observed in magnocellular supraoptic neurons of flight animals on the day of landing compared to control animals. These include increased c-Fos expression, larger nucleoli and cytoplasm, and higher volume occupied in the neuronal perikaryon by mitochondriae, endoplasmic reticulum, Golgi apparatus, lysosomes and cytoplasmic inclusions known as nematosomes. In contrast, the volume occupied by neurosecretory vesicles in the supraoptic neuronal perikarya was significantly decreased in flight rats. This decrease was associated with a significant decrease in oxytocin and vasopressin immunoreactive levels, suggestive of an increased hormonal release. Vasopressin levels, cytoplasmic volume and c-Fos expression returned to control levels by 18 weeks after landing. These reversible effects were probably associated to osmotic stimuli resulting from modifications in the volume and distribution of extracellular fluids and plasma during flight and landing. However, oxytocin levels were still reduced at 18 weeks after landing in flight animals compared to controls. This indicates that space flight during prepuberal age may induce irreversible modifications in the regulation of oxytocinergic neurons, which in turn may result in permanent endocrine and behavioral impairments.

Adverse metabolic effects of a hypercaloric, high-fat diet in rodents precede observable changes in body weight.

PubMed

McDonald, Sarah D; Pesarchuk, Eric; Don-Wauchope, Andrew; El Zimaity, Hala; Holloway, Alison C

2011-09-01

Although a high-fat diet (HFD) is recognized as an important contributor to obesity, human research is limited by confounders such as income, whereas animal research has typically examined diet during specific developmental periods rather than throughout the lifespan. We hypothesized that the use of an HFD in short-term studies as has been commonly done in animals does not adequately reflect the lifelong dietary patterns seen frequently in humans with consequent metabolic disturbances. We examined the impact of HFD from weaning until 39 weeks (middle age) on the metabolism of male rats. At 7, 26, and 39 weeks, glucose tolerance tests were performed, a subset of animals was euthanized, and serum and tissues were collected. After 4 weeks, preceding increased body weight, HFD animals had increased intra-abdominal fat, triglycerides, and hyperglycemia. Hyperinsulinemia was insufficient to maintain normoglycemia, and beta cell mass and glucagon-like peptide 1 decreased over time in HFD and control animals. Despite lacking significant lipid abnormalities, nonalcoholic fatty liver disease was evident by 39 weeks. Our HFD model demonstrated that significant metabolic abnormalities may go undetected by current standard screening such as weighing and biochemistry. Copyright © 2011 Elsevier Inc. All rights reserved.

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 in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

PubMed

Lozano, E; Strauss, M; Spina, R; Cifuente, D; Tonn, C; Rivarola, H W; Sosa, M A

2016-02-01

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biological impact of low dose-rate simulated solar particle event radiation in vivo.

PubMed

Chang, P Y; Doppalapudi, R; Bakke, J; Wang, A; Menda, S; Davis, Z

2010-08-01

C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure.

Promotional effects of CO2 laser on neoplastic lesions in hamsters

NASA Astrophysics Data System (ADS)

Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles

1991-06-01

Surgical incision may have promotional effects on neoplastic lesions, possibly through release of tissue growth factors (e.g., EGF, FGF(beta) , IGF, TGF(alpha) ). The CO2 laser may precipitate altered release of these factors. To test this, .5 cm laser, and scalpel incisions were made into fields treated by application of .5% DMBA in acetone, 3 times a week for 6 weeks (group 1) and 12 weeks (group 2). DMBA is a complete carcinogen (initiator and promoter). At 6 weeks, chemically, but not histologically, definable premalignant lesions are seen. Treatment for 12 weeks causes histologic neoplasia which can be graded with T-N-M classification. For both groups, the surgical sites were examined clinically and histologically 4 weeks post-op in a blind fashion. Standard criteria were utilized for defining neoplasia. For group 1, 3 out of 6 laser treated animals developed large exophytic squamous cell carcinomas, but no lesions developed in 12 contralateral, 3 control and 3 scalpel treated pouches. For group 2, 12 of 16 laser treated animals developed tumor with mean grade of 1.75 and mean size of 7.4 mm, 5 of 6 scalpel treated animals developed tumor with mean grade of 1.83 and mean size of 3.6 mm and 3 of 6 control animals developed tumor with mean grade of 1.00 and mean size of 1.5 mm. By the Student 't' test on the binomial distribution lasers cause significant promotion (p < .01). These results suggest that laser surgery may have earlier and more profound promotional effects than scalpel on initiated cells relative to tumor size in the vicinity of the wound site by increased release of growth factors.

Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine in drinking water.

PubMed

Tatematsu, M; Yamamoto, M; Shimizu, N; Yoshikawa, A; Fukami, H; Kaminishi, M; Oohara, T; Sugiyama, A; Ikeno, T

1998-02-01

An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

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

Treadmill exercise alleviates chronic mild stress-induced depression in rats.

PubMed

Lee, Taeck-Hyun; Kim, Kijeong; Shin, Mal-Soon; Kim, Chang-Ju; Lim, Baek-Vin

2015-12-01

Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2'-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

PubMed

Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

2010-06-01

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Kanazawa, N.; Lutze-Mann, L.; Winegar, R.

2001-01-01

Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

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.

Biodegradable esophageal stent placement does not prevent high-grade stricture formation after circumferential mucosal resection in a porcine model.

PubMed

Pauli, Eric M; Schomisch, Steve J; Furlan, Joseph P; Marks, Andrea S; Chak, Amitabh; Lash, Richard H; Ponsky, Jeffrey L; Marks, Jeffrey M

2012-12-01

Advanced esophageal dysplasia and early cancers have been treated traditionally with esophagectomy. Endoscopic esophageal mucosectomy (EEM) offers less-invasive therapy, but high-degree stricture formation limits its applicability. We hypothesized that placement of a biodegradable stent (BD-stent) immediately after circumferential EEM would prevent stricturing. Ten pigs (five unstented controls, five BD-stent) were utilized. Under anesthesia, a flexible endoscope with a band ligator and snare was used to incise the mucosa approximately 20 cm proximal to the lower esophageal sphincter. A 10-cm, circumferential, mucosal segment was dissected and excised by using snare electrocautery. In the stented group, an 18-×120-mm, self-expanding, woven polydioxanone stent (ELLA-CS, Hradec-Kralove) was deployed. Weekly esophagograms evaluated for percent reduction in esophageal diameter, stricture length, and proximal esophageal dilation. Animals were euthanized when the stricture exceeded 80% and were unable to gain weight (despite high-calorie liquid diet) or at 14 weeks. The control group rapidly developed esophageal strictures; no animal survived beyond the third week of evaluation. At 2 weeks post-EEM, the BD-stent group had a significant reduction in esophageal diameter (77.7 vs. 26.6%, p < 0.001) and degree of proximal dilation (175 vs. 131%, p = 0.04) compared with controls. Survival in the BD-stent group was significantly longer than in the control group (9.2 vs. 2.4 weeks, p = 0.01). However, all BD-stent animals ultimately developed clinically significant strictures (range, 4-14 weeks). Comparison between the maximum reduction in esophageal diameter and stricture length (immediately before euthanasia) demonstrated no differences between the groups. Circumferential EEM results in severe stricture formation and clinical deterioration within 3 weeks. BD-stent placement significantly delays the time of clinical deterioration from 2.4 to 9.2 weeks, but does not affect the maximum reduction in esophageal diameter or proximal esophageal dilatation. The timing of stricture formation in the BD-stent group correlated with the loss radial force and stent disintegration.

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.

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

PubMed

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

2011-06-01

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

Evaluating the dose effects of a longitudinal micro-CT study on pulmonary tissue in C57BL/6 mice

NASA Astrophysics Data System (ADS)

Detombe, Sarah A.; Dunmore-Buyze, Joy; Petrov, Ivailo E.; Drangova, Maria

2012-03-01

Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

Innocuity and immune response to Brucella melitensis Rev.1 vaccine in camels (Camelus dromedarius)

PubMed Central

Benkirane, A.; Idrissi, A.H. El; Doumbia, A.; de Balogh, K.

2014-01-01

A field trial was conducted in a camel brucellosis-free herd to evaluate antibody response to the Brucella melitensis Rev.1 vaccine in camels and assess shedding of the vaccine strain in milk. Twenty eight camels were divided into four groups according to their age and vaccination route. Groups A (n=3) and B (n=3) consisted of non-pregnant lactating female camels, vaccinated through subcutaneous and conjunctival routes, respectively. Groups C (n=10) consisted of 8-11 months old calves vaccinated through conjunctival route. The rest of the herd (n=12) composed of female and young camels were not vaccinated and were considered as the control group. Each animal from groups A, B and C was given the recommended dose of 2 × 109 colony forming units of Rev.1 vaccine irrespective of age or route of vaccination. Blood samples were collected from all the animals at the time of vaccination and at weekly, bi-weekly and monthly interval until 32 weeks post vaccination and from controls at weeks 8 and 24. The serological tests used were modified Rose Bengal Test, sero-agglutination test, and an indirect Enzyme Linked Immunosorbent Assay. Milk samples were collected from all vaccinated female camels and tested for the presence of Rev.1 vaccine strain. Most vaccinated animals started to show an antibody response at week 2 and remained positive until week 16. By week 20 post-vaccination all animals in the three groups were tested negative for Brucella antibodies. Bacteriological analysis of milk samples did not allow any isolation of Brucella melitensis. All samples were found Brucella negative in PCR analysis. The results of this study indicate that the Rev.1 vaccine induces seroconversion in camels. Rev.1 vaccine strain is not excreted in the milk of camels. These findings are promising as to the safe use of the Rev.1 vaccine in camels. PMID:26623347

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.

Onset of immunity in kittens after vaccination with a non-adjuvanted vaccine against feline panleucopenia, feline calicivirus and feline herpesvirus.

PubMed

Jas, D; Aeberlé, C; Lacombe, V; Guiot, A L; Poulet, H

2009-10-01

The induction of a quick onset of immunity against feline parvovirus (FPV), feline herpesvirus (FHV) and feline calicivirus (FCV) is critical both in young kittens after the decline of maternal antibodies and in cats at high risk of exposure. The onset of immunity for the core components was evaluated in 8-9 week old specific pathogen free kittens by challenge 1 week after vaccination with a combined modified live (FPV, FHV) and inactivated (FCV) vaccine. The protection obtained 1 week after vaccination was compared to that obtained when the challenge was performed 3-4 weeks after vaccination. The protocol consisted of a single injection for vaccination against FPV and two injections 4 weeks apart for FHV and FCV. At 1 week after vaccination, the kittens showed no FPV-induced clinical signs or leukopenia following challenge, and after FCV and FHV challenges the clinical score was significantly lower in vaccinated animals than in controls. Interestingly, the relative efficacy of the vaccination was comparable whether the animals were challenged 1 week or 3-4 weeks after vaccination, indicating that the onset of protection occurred within 7 days of vaccination. Following the 1-week challenge, excretion of FPV, FHV and FCV was significantly reduced in vaccinated cats compared to control kittens, confirming the onset of immunity within 7 days of vaccination.

Role of 3D animation in periodontal patient education: a randomized controlled trial.

PubMed

Cleeren, Gertjan; Quirynen, Marc; Ozcelik, Onur; Teughels, Wim

2014-01-01

This randomized controlled parallel trial investigates the effect of 3D animation on the increase and recall of knowledge on periodontitis by patients with periodontitis. The effects of a 3D animation (3D animation group) were compared with narration and drawing (control group) for periodontal patient education. A total of 68 periodontitis patients were stratified according to educational level and then randomly allocated to control or 3D animation groups. All patients received: (1) a pre-test (baseline knowledge), (2) a patient education video (3D animation or control video), (3) a post-test (knowledge immediately after looking at the video), and (4) a follow-up test (knowledge recall after 2 weeks). Each test contained 10 multiple-choice questions. There was no significant difference in baseline knowledge. Patients receiving the 3D animations had significantly higher scores for both the post-test and the follow-up test, when compared with patients receiving sketch animations. 3D animations are more effective than real-time drawings for periodontal patient education in terms of knowledge recall. 3D animations may be a powerful tool for assisting in the information process. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

1985-09-01

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

Antiinflammatory agents protect opossum esophagus during radiotherapy. [Cobalt 60

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

Northway, M.G.; Eastwood, G.L.; Libshitz, H.I.

Eighteen opossums received 2250 rad /sup 60/Co to the entire esophagus and lower esophageal sphincter. Animals received treatment with 600 mg aspirin, 25 mg/kg hydrocortisone, or saline before irradiation and twice daily for 1 week after irradiation. At 10 days postirradiation, animals were evaluated for signs of acute esophagitis by esophagoscopy and barium esophagram. Each animal was then killed and the esophagus removed and evaluated histologically. Animals treated with either aspirin or hydrocortisone had significantly milder esophagitis than control irradiated animals.

A novel animal model for skin flap prelamination with biomaterials

NASA Astrophysics Data System (ADS)

Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun

2016-09-01

Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible.

[Neuronal LHRH system activity in an animal model of growth retardation].

PubMed

Compagnucci, Cecilia Vanesa; Compagnucci, Gabriela Edith; Lezón, Christian Esteban; Chiarenza, Ana Patricia; Elverdin, Juan Carlos; Boyer, Patricia Mónica

2010-05-01

Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction. Copyright (c) 2009 SEEN. Published by Elsevier Espana. All rights reserved.

Providing straw to allow exploratory behaviour in a pig experimental system does not modify putative indicators of positive welfare: peripheral oxytocin and serotonin.

PubMed

Marcet Rius, M; Cozzi, A; Bienboire-Frosini, C; Teruel, E; Chabaud, C; Monneret, P; Leclercq, J; Lafont-Lecuelle, C; Pageat, P

2018-01-22

Numerous studies have shown that providing straw to pigs can reduce undesirable behaviours such as aggression, tail biting and stereotypy. The measurement of various neuromodulators can be helpful in assessing the development of positive behaviours and overall animal welfare. The oxytocin release is frequently linked to positive emotions and positive welfare. It has been suggested that oxytocin modulates the serotoninergic system. This study aims to investigate the potential effect of straw provision in pigs on peripheral levels of oxytocin and serotonin. In total, 18 mini-pigs were involved in an exploratory study conducted in two parallel groups, Enriched (n=10) and Control (n=8) groups. Pigs were divided by group and housed in pens of two individuals. Straw was provided continuously only in Enriched group and renewed each day for 2 weeks. Two blood samples were drawn from each animal 5 to 10 min before providing the straw, and 15 min after providing straw, during the 1st week, to analyse peripheral changes in oxytocin and serotonin before and after straw provision, and determine the existence of a putative short-term effect. The same procedure was carried out for Control group, without straw provision. Long-term effects of straw provision were also examined using blood samples drawn at the same hour from each animal in the 2nd and 3rd weeks. During this time, animals had the permanent possibility to explore the straw in Enriched group but not in Control group. At the end of each week, one animal-keeper completed two visual analogue scales for each mini-pig regarding the difficulty/ease to work with and handle it and its trust in humans. Results showed peripheral oxytocin increases in both groups after 2 weeks (P=0.02). Results did not demonstrate any effect of providing straw to allow exploratory behaviour on peripheral serotonin. Other results were not significant. This preliminary study explored the relationship between peripheral oxytocin and serotonin and the presence of straw that allow pigs to perform exploratory behaviour, suggesting that there was no relationship between them. Some future studies may include crossing oxytocin and serotonin with other parameters, such as behavioural measures, to obtain more information about the true state of the animal and any possible relationship with pig welfare.

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.

Role of postnatal dietary sodium in prenatally programmed hypertension.

PubMed

Stewart, Tyrus; Ascani, Jeannine; Craver, Randall D; Vehaskari, V Matti

2009-09-01

In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43-49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal "reprogramming" of the hypertension.

Systemic immunity influences hearing preservation in cochlear implantation.

PubMed

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

2012-06-01

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

Cardiovascular Responses and Differential Changes in Mitogen-Activated Protein Kinases Following Repeated Episodes of Binge Drinking

PubMed Central

Gu, Lianzhi; Fink, Anne M.; Chowdhury, Shamim A.K.; Geenen, David L.; Piano, Mariann R.

2013-01-01

Aims: Excessive alcohol use in the form of binge drinking is associated with many adverse medical outcomes. Using an animal model, the primary objective of this study was to determine the effects of repeated episodes of binge drinking on myocardial structure, blood pressure (BP) and activation of mitogen-activated protein kinases (MAPKs). The effects of carvedilol, a beta-adrenergic blocker, were also examined in this animal model of binge drinking. Methods: Rats were randomized into three groups: control, binge and binge + carvedilol (20 mg/kg). Animals received intragastric administration of 5 g ethanol/kg in the morning × 4 days (Monday–Thursday) followed by no ethanol on Friday–Sunday. Animals were maintained on the protocol for 5 weeks. BP was measured using radiotelemetry methods. Animals underwent echocardiography at baseline, 2.5 and 5 weeks. Myocardial MAPKs were analyzed at 5 weeks using western blot techniques. Results: Over the course of 5 weeks, binge drinking was associated with significant transient increases in BP that were greater at 4 and 5 weeks compared with earlier time points. Carvedilol treatment significantly attenuated the binge-induced transient increases in BP at 4 and 5 weeks. No significant changes were found in echocardiographic parameters at any time period; however, binge drinking was associated with increased phosphorylation of p38 MAPK, which was blocked by carvedilol treatment. Conclusion: Repeated episodes of binge drinking result in progressive and transient increases in BP, no change in myocardial structure and differential regulation of MAPK activation. PMID:22878590

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

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

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.

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.

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

PubMed Central

Wicher, V; Wicher, K

1977-01-01

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

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.

Bariatric Arterial Embolization with Non-spherical Polyvinyl Alcohol Particles for Ghrelin Suppression in a Swine Model

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

Kim, Jae Min; Kim, Man-Deuk, E-mail: mdkim@yuhs.ac; Han, Kichang

PurposeTo evaluate the effect of bariatric arterial embolization (BAE) with non-spherical polyvinyl alcohol (PVA) particles on systemic ghrelin levels, weight change, and gastric ulceration risk in a swine model.Materials and MethodsFrom March 2014 to February 2015, ten healthy swine were used in the study (mean weight 31.5 kg; range 24.0–41.5 kg). The animals were randomly assigned to two groups: the embolized group (n = 5) in which BAE was performed and the control group (n = 5). In the embolized group, BAE was performed by selectively infusing 150–250 or 50–150 μm PVA into the gastric arteries that supplied the fundus of the stomach. In the control group,more » a sham procedure was performed with saline infusion. Plasma ghrelin levels were prospectively obtained at baseline and every 2 weeks thereafter. Endoscopy was performed 3 weeks after BAE to see whether any gastric ulcer occurred. To determine the durability of the occluded arteries, repeated celiac trunk angiography was performed 8 weeks after BAE. Then, all the swine were killed and necropsies were performed.ResultsThe mean post-procedure ghrelin value decreased by 370.0 pg/mL in the embolized group at week 3 (mean 536.0 ± 334.3 pg/mL) and week 5 (mean 515.0 ± 150.0 pg/mL, p < 0.05) relative to baseline (880.0 ± 559.5 pg/mL), respectively, but ghrelin levels were not significantly decreased between the embolized and control groups. There was a significant body weight change as follows: 35.1 ± 9.5 to 46.6 ± 15.7 kg and 31.8 ± 5.8 to 41.2 ± 6.6 kg at baseline and endpoint in the control and embolized groups, respectively (p < 0.05). However, the difference between groups was not significant at endpoint. In the embolized group, ulcerations were identified in three animals (60%) and the recanalization of the embolized arteries was noted on follow-up angiography in three animals (60%), respectively.ConclusionBAE with PVA particles can transiently suppress ghrelin levels in embolized animals, but levels are not significantly different compared to controls. Stomach ulcerations were identified in 60% of the embolized animals.« less

Bariatric Arterial Embolization with Non-spherical Polyvinyl Alcohol Particles for Ghrelin Suppression in a Swine Model.

PubMed

Kim, Jae Min; Kim, Man-Deuk; Han, Kichang; Muqmiroh, Lailatul; Kim, Seung Up; Kim, Gyoung Min; Kwon, Joonho; Park, Sung Il; Won, Jong Yun; Lee, Do Yun

2017-05-01

To evaluate the effect of bariatric arterial embolization (BAE) with non-spherical polyvinyl alcohol (PVA) particles on systemic ghrelin levels, weight change, and gastric ulceration risk in a swine model. From March 2014 to February 2015, ten healthy swine were used in the study (mean weight 31.5 kg; range 24.0-41.5 kg). The animals were randomly assigned to two groups: the embolized group (n = 5) in which BAE was performed and the control group (n = 5). In the embolized group, BAE was performed by selectively infusing 150-250 or 50-150 μm PVA into the gastric arteries that supplied the fundus of the stomach. In the control group, a sham procedure was performed with saline infusion. Plasma ghrelin levels were prospectively obtained at baseline and every 2 weeks thereafter. Endoscopy was performed 3 weeks after BAE to see whether any gastric ulcer occurred. To determine the durability of the occluded arteries, repeated celiac trunk angiography was performed 8 weeks after BAE. Then, all the swine were killed and necropsies were performed. The mean post-procedure ghrelin value decreased by 370.0 pg/mL in the embolized group at week 3 (mean 536.0 ± 334.3 pg/mL) and week 5 (mean 515.0 ± 150.0 pg/mL, p < 0.05) relative to baseline (880.0 ± 559.5 pg/mL), respectively, but ghrelin levels were not significantly decreased between the embolized and control groups. There was a significant body weight change as follows: 35.1 ± 9.5 to 46.6 ± 15.7 kg and 31.8 ± 5.8 to 41.2 ± 6.6 kg at baseline and endpoint in the control and embolized groups, respectively (p < 0.05). However, the difference between groups was not significant at endpoint. In the embolized group, ulcerations were identified in three animals (60%) and the recanalization of the embolized arteries was noted on follow-up angiography in three animals (60%), respectively. BAE with PVA particles can transiently suppress ghrelin levels in embolized animals, but levels are not significantly different compared to controls. Stomach ulcerations were identified in 60% of the embolized animals.

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.

Critical periods for marihuana-induced intrauterine growth retardation in the rat.

PubMed

Abel, E L; Bush, R; Dintcheff, B A; Ernst, C A

1981-01-01

Pregnant rats were intubated with marihuana extract (20, 200 mg/kg) throughout gestation. Control animals were intubated with vehicle (olive oil). Control animals and animals treated with the lower dose of drug were pair-fed and pair-watered to animals treated with the high dose. At parturition, pups were counted, weighed, culled, and assigned to nondrug-treated dams. Marihuana reduced food and water consumption and maternal weight gain. Pup weight at birth was reduced and neonatal mortality was increased in offspring exposed during the third week of gestation or throughout gestation. Litter size, postnatal mortality and weight at weaning were not significantly affected.

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

PubMed

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

2014-03-01

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

Evaluation of Bone Healing After Osteotomies Prepared With Er:YAG Laser in Contact and Noncontact Modes and Piezosurgery--An Animal Study.

PubMed

Gabrić, Dragana; Blašković, Marko; Gjorgijevska, Elizabeta; Mladenov, Mitko; Tašič, Blaž; Jurič, Ivona Bago; Ban, Ticijana

2016-01-01

To analyze the healing of bone tissue treated with Er:YAG laser contact and noncontact modes of and piezosurgery in a rat model using triangular laser profilometry. Twenty-four 10-week-old adult male Wistar rats were used in the study. Three osteotomies on the medial part of tibia were performed in each animal, 1 in the right tibia and 2 in the left tibia. The osteotomies were performed with a piezoelectric device set at maximal power and the Er:YAG laser in contact mode (power, 7.5 W; pulse energy, 375 mJ; repetition rate, 20 Hz; MSP mode) and noncontact mode (power, 7.5 W; pulse energy, 750 mJ; repetition rate, 10 Hz; QSP mode) with a novel type of circular, digitally controlled handpiece (x-Runner). After surgery, 6 animals were immediately euthanized (group 1), and the others were euthanized after 1 week (group 2, n = 6), 2 weeks (group 3, n = 6), and 3 weeks (group 4, n = 6). Bone healing after osteotomy was analyzed using a 3-dimensional laser scanning technique (ie, laser triangulation profilometry). The volume reduction rates are similar for all 3 techniques (0.2 to 0.25 mm(3) per week). Greater volume reduction of 0.25 mm3 per week was observed for the Er:YAG laser in noncontact mode (x-Runner). After 3 weeks, almost complete healing of the prepared osteotomy was observed. Within the limitations of this study, the osteotomies performed by the Er:YAG laser in digitally controlled noncontact mode healed the fastest. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Time-dependent alteration in cromakalim-induced relaxation of corpus cavernosum from streptozocin-induced diabetic rats.

PubMed

Ghasemi, Mehdi; Sadeghipour, Hamed; Asadi, Shahrzad; Dehpour, Ahmad Reza

2007-09-01

The purpose of the present study was to investigate the relaxant responses to the ATP-sensitive potassium (K(ATP)) channel opener cromakalim in corpus cavernosum strips from 1-, 2-, 4-, 6-, and 8-week streptozocin-induced diabetic rats. Cromakalim (1 nM-0.1 mM) produced concentration-dependent relaxation in phenylephrine (7.5 microM)-precontracted isolated rat corporal strips. Compared with age-matched control animals, a significant enhancement in cromakalim-induced relaxation of corpus cavernosum was observed in 2-week diabetic animals, whereas the relaxant responses to cromakalim were decreased in 6-and 8-week diabetic animals. However, the cromakalim-induced relaxation was not altered in either 1-week or 4-week rat corporal strips in comparison with corresponding age-matched non-diabetic groups. Preincubation with the K(ATP) channel blocker glibenclamide (10 microM) significantly inhibited the cromakalim-induced relaxation in both non-diabetic and diabetic rat corpus cavernosum, but neither the voltage-dependent K(+) channel (K(V)) antagonist 4-aminopyridine (1 mM) nor the calcium-activated K(+) channel (K(Ca)) antagonist charybdotoxin (0.1 microM) had significant effect on cromakalim-induced relaxation in both control and diabetic rat corporal strips. Relaxation responses to the nitric oxide donor sodium nitroprusside (1 nM-0.1 mM) in diabetic rat corpus cavernosum were similar to that of age-matched controls. These data demonstrated that the relaxant responses to cromakalim were altered in diabetic cavernosal strips in a time dependent manner, suggesting that the period of diabetes mellitus may play a key role in the K(ATP) channels function in rat corpus cavernosum.

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.

A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

PubMed

Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

2015-01-14

Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

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

Borowsky, A D; Dingley, K; Ubick, E

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIPmore » showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.« less

Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

PubMed

Leclercq, Karine; Kaminski, Rafal M

2015-08-01

Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks after SE. Perampanel and phenytoin showed almost comparable protective effects in all groups of mice. These experiments confirm that prior SE may have an impact on both potency and efficacy of AEDs and indicate that this effect may be dependent on the underlying epileptogenic processes. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of systemic stress on orthodontic tooth movement.

PubMed

Gameiro, Gustavo Hauber; Nouer, Darcy Flávio; Pereira-Neto, Joáo Sarmento; Urtado, Marília Bertoldo; Novaes, Pedro Duarte; de Castro, Margaret; Veiga, Maria Cecília Ferraz Arruda

2008-11-01

To determine if systemic stress affects the biological reactions occurring during orthodontic tooth movement. Four groups of male 10 week-old Wistar rats were used. Group A animals (N=10) were restrained for one hour per day for 40 days; Group B animals (N=10) were restrained for one hour per day for three days; Group C (N=10) and Group D (N=8) animals were unrestrained. The upper left first molars in the rats in Groups A (long-term stress), B (short-term stress) and C (control) were moved mesially during the last 14 days of the experiment. The animals in Group D (N=8) were used for body weight and hormonal dosage comparisons only. They were not subjected to any stress and did not have appliances fitted. All animals were killed at 18 weeks of age and blood collected for measurement of plasma corticosterone. Tooth movement was measured with an electronic caliper. The right and left hemi-maxillae of five rats from each group were removed and the number of tartrate-resistant acid phosphatase (TRAP) positive cells, defined as osteoclasts, adjacent to the mesial roots of the upper first molars counted. The contralateral side in each animal served as the control (split-mouth design). Corticosterone levels were significantly higher in the stressed groups (Groups A and B) than in the control group (Group C). Tooth movement was significantly greater in Group A (long-term stress) compared with Group B (short-term stress) and Group C (control), which did not differ from each other. There were significantly more osteoclasts in the long-term stress group than in the short-term stress and control groups. Persistent systemic stress increases bone resorption during orthodontic tooth movement. Systemic stress may affect the rate of tooth movement during orthodontic treatment.

Chronic rotator cuff injury and repair model in sheep.

PubMed

Coleman, Struan H; Fealy, Stephen; Ehteshami, John R; MacGillivray, John D; Altchek, David W; Warren, Russell F; Turner, A Simon

2003-12-01

Most rotator cuff surgery is performed on chronic tears. As there is no animal model in which to examine the physiology of muscle and tendon injury and repair in this setting, we developed a chronic rotator cuff injury model in sheep. The infraspinatus tendon was released in thirty-six female sheep. Biopsy specimens were obtained from the muscle and were analyzed for fat content. The force generated by the muscle with supramaximal stimulation was recorded intraoperatively. A control group (twelve sheep) underwent an immediate tendon repair. In the remaining twenty-four sheep, the tendon was wrapped in a dura substitute to prevent scarring and was repaired at six weeks (eight sheep) and eighteen weeks (sixteen sheep) after release. In the immediate repair group, four animals were killed at six weeks; four, at twelve weeks; and four, at twenty weeks. In the six-week delayed repair group, four animals were killed at twelve weeks and four were killed at twenty weeks after the repair. In the eighteen-week delayed repair group, eight animals were killed at twelve weeks; four, at twenty weeks; and four, at thirty weeks after the repair. Muscle biopsies and testing were repeated prior to killing of the animals. The average force of muscle contraction decreased 3.6 lb (1.6 kg) by six weeks after the injury and 3.9 lb (1.8 kg) by eighteen weeks after the injury. After the repair, the force of contraction in the six-week group improved by 0.8 lb (0.4 kg) at twelve weeks postoperatively and by 1.3 lb (0.6 kg) at twenty weeks postoperatively. In contrast, no improvement occurred in the eighteen-week group until thirty weeks after the repair, at which time a 0.9-lb (0.4-kg) improvement was noted. There was a twelvefold increase in intramuscular fat concentration; this lipid infiltration was partially reversed after the tendon repair. Isolated tendon samples demonstrated an increase in the modulus of elasticity after chronic detachment that partially corrected after the tendon repair in the earlier (six-week) repair group. We found that earlier repair of the tendon results in a more rapid recovery of both muscle function and tendon elasticity compared with a more delayed repair. We concluded that there may be a "point of no return" in rotator cuff injury after which the elasticity of the muscle-tendon unit does not return to normal.

Salt adaptation in Bufo bufo

PubMed Central

Ferreira, H. G.; Jesus, C. H.

1973-01-01

1. The capacity of adaptation of toads (Bufo bufo) to environments of high salinity was studied and the relative importance of skin, kidney and urinary bladder in controlling the balance of water and salt was assessed. 2. Toads were kept in NaCl solutions of 20, 50, 110, 150 and 220 mM and studied in their fourth week of adaptation. A group of animals considered as `control' was kept in wet soil with free access to water. Plasma, ureter urine, and bladder and colon contents were analysed for sodium, potassium, chloride and osmolality, and total body sodium and water were determined. Absorption of water and 22Na through the skin, and water flow and sodium excretion through the ureter, of intact animals was studied. Hydrosmotic water transport through the isolated urinary bladder of `control' and adapted animals was determined. The effects of pitressin and aldosterone on the water and sodium balance are described. 3. The survival rates of toads kept in saline concentrations up to 150 mM were identical to that of `control' animals, but half of the animals kept in 220 mM died within 4 weeks. 4. There is a linear correlation between the sodium concentrations and osmolality of plasma and of the external media. 5. The sodium concentration in colon contents rose with rising external concentrations, up to values higher than the values in plasma. 6. Sodium concentrations and osmolalities of ureter and bladder urine increased in adapted animals, the values for bladder urine becoming much higher than those for ureter urine in animals adapted to 110, 150 and 220 mM. 7. Total body water, as a percentage of total weight was kept within very narrow limits, although the total body sodium increased with adaptation. 8. Absorption of water through the skin for the same osmotic gradients was smaller in adapted than in `control' animals. 9. The ureteral output of water of toads adapted to 110 and 150 mM-NaCl was larger than the water absorption through the skin. 10. Skin absorption of sodium was lower in animals adapted to concentrated saline solutions than in `control' animals. 11. Sodium output by the ureter was identical to skin absorption in `control' animals adapted to 20, 50 and 110 mM-NaCl but was higher in animals adapted to 150 mM-NaCl. 12. Aldosterone increased the absorption of sodium in `control' and adapted toads, but at all dose levels absorption by control was greater than by adapted animals. 13. The stimulation of water absorption by vasopressin in vivo or in isolated bladders was not modified in animals adapted to high salinities. PMID:4633911

The influence of natural short photoperiodic and temperature conditions on plasma thyroid hormones and cholesterol in male Syrian hamsters

NASA Astrophysics Data System (ADS)

Vaughan, M. K.; Brainard, G. C.; Reiter, R. J.

1984-09-01

Adult male Syrian hamsters were subjected to 1, 3, 5, 7 or 11 weeks of either natural winter conditions or rigorously controlled laboratory conditions (LD 10∶14; 22 ± 2‡C). Although both groups of hamsters gained weight over the course of the experiment, hamsters housed indoors were significantly heavier after 5 weeks of treatment compared to their outdoors counterparts. Animals housed under natural conditions exhibited a significant decrease in circulating levels of thyroxine (T4) and a rapid rise in triiodothyronine (T3) levels; the free T4 and free T3 index (FT4I and FT3I) mirrored the changes in circulating levels of the respective hormones. Laboratory-housed animals had a slight rise in T4 and FT4I at 3 weeks followed by a slow steady decline in these values; T3 and FT3I values did not change remarkably in these animals. Plasma cholesterol declined steadily over the course of the experiment in laboratory-maintained animals but increased slightly during the first 5 weeks in animals under natural conditions. Since the photoperiodic conditions were approximately of the same duration in these 2 groups, it is concluded that the major differences in body weight, thyroid hormone values and plasma cholesterol are due to some component (possibly temperature) in the natural environment.

Effects of Ficus asperifolia on normal rat estrus cyclicity

PubMed Central

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

2013-01-01

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

Temporal changes in the bacterial community of animal feces and their correlation with stable fly oviposition, larval development, and adult fitness

PubMed Central

Albuquerque, Thais A.; Zurek, Ludek

2014-01-01

Stable flies are blood-feeding insects with a great negative impact on animals world wide. Larvae develop primarily in animal manure and bacteria are essential for larval development; however, the principle of this dependence is not understood. We hypothesized that as the microbial community of animal manure changes over time, it plays an important role in stable fly fitness. Two-choice bioassays were conducted using 2 week old horse manure (control) and aging horse manure (fresh to 5 week old) to evaluate the effect of manure age on stable fly oviposition. Our data showed that fresh feces did not stimulate oviposition and that the attractiveness increased as manure aged but started to decline after 3 weeks. Bioassays assessing the effect of manure age at the time of oviposition on larval development demonstrated that 1–3 week old manure supported larval development significantly better than fresh, 4, and 5 week old manure. In addition, adult fitness (body size) was significantly higher in flies from 1 and 2 week old manure comparing to that of all other treatments. Analysis of the bacterial community of aging horse manure by 454-pyrosequencing of 16S rDNA revealed a great reduction in bacterial diversity and richness from fresh to 1–5 week old manure and a major shift from strict anaerobes in fresh manure to facultative anaerobes and strict aerobes in aged manure. Overall, the microbial community of 2 and 3 week old horse manure with its dominant bacterial taxa Rhizobium, Devosia, and Brevundimonas stimulated stable fly oviposition the most and provided a suitable habitat for larval development. These bacteria represent the candidates for studies focused on better understanding of stable fly – microbial interactions. PMID:25426108

Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

PubMed

Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

1998-01-01

The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

Non-invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin-converting enzyme inhibition in diabetic rats

PubMed Central

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

2002-01-01

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril. PMID:11790818

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.

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

PubMed Central

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

2017-01-01

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

Tamoxifen mutagenesis and carcinogenesis in livers of lambda/lacI transgenic rats: selective influence of phenobarbital promotion.

PubMed

Styles, J A; Davies, R; Fenwick, S; Walker, J; White, I N; Smith, L L

2001-01-10

Administration of tamoxifen (TAM) (20 mg/kg per day p.o.) for 6 weeks to female lambda/lacI transgenic rats caused a 4-fold increase in mutation frequency (MF) at the lacI gene locus in the livers of dosed animals compared with controls. After cessation of dosing, the MF showed a further increase with time at 2, 12 and 24 weeks, respectively. Phenobarbital promotion of similarly treated animals resulted in no increase in mutation frequency compared with TAM alone. Treatment with phenobarbital or TAM+phenobarbital resulted in time-dependent increases in liver weight compared with the corresponding controls. There was an increase in cell proliferation in the phenobarbital and TAM+phenobarbital groups, and at 24 weeks in the TAM dosed animals compared with controls. There was also a progressive increase in the number of GST-P expressing foci in the livers of TAM and TAM + phenobarbital rats compared with controls. The induction of cell proliferation and GSTP foci in the rat liver by phenobarbital is consistent with its ability to promote tamoxifen-initiated liver tumours in the rat. If the lacI gene is regarded as being representative of the rat genome in general (albeit that the gene is bacterial) the above observations suggest that promotion by tamoxifen confers selective advantage on mutated genes at loci that contribute to the tumour phenotype and that promotion of rat liver tumours by tamoxifen is not dependent simply upon the enhancement of cellular proliferation.

Efficacy evaluation of a commercial neem cake for control of Haematobia irritans on Nelore cattle.

PubMed

Chagas, Ana Carolina de Souza; Oliveira, Márcia Cristina de Sena; Giglioti, Rodrigo; Calura, Fernando Henrique; Ferrenzini, Jenifer; Forim, Moacir Rossi; Barros, Antonio Thadeu Medeiros de

2010-01-01

Much attention has been given to the development of botanical insecticides to provide effective natural control of cattle ectoparasites without harming animals, consumers, and environment. This study evaluated the efficacy of a commercial neem cake in controlling Haematobia irritans infestation on cattle. The study was conducted at the Embrapa Southeast Cattle Research Center (CPPSE), in São Carlos, SP, Brazil, from April to July 2008. The neem cake mixed in mineral salt in a 2% concentration was provided to 20 Nelore cows during nine weeks and had its efficacy evaluated by comparison of the infestation level against a control group. Fly infestations were recorded weekly by digital photographs of each animal from both groups and the number of flies was later counted in a computer-assisted image analyzer. Quantification of neem cake components by high-performance liquid chromatography revealed the presence of azadirachtin (421 mg.kg(-1)) and 3-tigloyl-azadirachtol (151 mg.kg(-1)) in the tested neem cake. Addition of the 2% neem cake reduced mineral salt intake in about 22%. The 2% neem cake treatment failed to reduce horn fly infestations on cattle during the 9-week study period.

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.

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

PubMed

Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

2016-06-30

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

[Impact of streptozotocininduced hyperglycemia on anxiety level and physical fatigue of Wistar rats].

PubMed

Sidorova, Yu S; Shipelin, V A; Zorin, S N; Mazo, V K; Petrov, N A; Kochetkova, A A

2015-01-01

The aim of the study was to evaluate type 2 diabetes medicamental biomodel in 70-days experiment. Control group animals were provided with water ad libitum throughout the experiment, experimental group animals for the first two weeks were provided with 20% solution of fructose ad libitum instead of water. On the 15th day, experimental group animals (average body weight 257±8 g) were injected abdominally with streptozotocin (STZ) in dosage 40 mg/kg of body weight. For the next three weeks on the 22nd, 28th and 36th days, glucose level in blood taken from the tail vein was measured using portable electrochemical glucometer. On the 37th day animals with blood glucose level 11.0 mmol/L or higher were included in experimental group for further research. On the 44th and 60th day control measurements of glucose level were conducted. On the 70th day animals were taken out of experiment by decapitation under ether anesthesia. The concentration of glucose, glycosylated hemoglobin, triglycerides, cholesterine, HLD and LDL were measured in blood serum. Additionally anxiety level of animals was evaluated before and after STZ injection using Elevated plusmaze. The comparison of physical fatigue of control and experimental groups was performed using treadmill. On the 37th day blood glucose concentration of control group animals was 6.6±0.4 mmol/L. 33% of animals (13 of 40) with glucose level 11.0 mmol/L or higher formed the experimental group (average glucose level 16.2±1.3 mmol/L), other 27 rats had normal glucose level. The anxiety level of diabetic rats was higher than in control group. Diabetic rats showed significantly lower physical fatigue than control rats. On the 44th and 60th day of experiment glucose level in experimental rats from group 2 (15.5±1.4 и 14.8±1.2 mmol/L) was significantly higher than of control animals (7.0±0.5 и 6.8±0.3 mmol/L). Glycated hemoglobin level in blood serum of diabetic group (7.2±0.7%) was significantly higher than of control group (3.3±0.2%). This proves the progression of stable long-term hyperglycemia. According to results represented model can be used for initial experimental evaluation of tested antidiabetic biologically active substances.

A novel conduit-based coaptation device for primary nerve repair.

PubMed

Bamba, Ravinder; Riley, D Colton; Kelm, Nathaniel D; Cardwell, Nancy; Pollins, Alonda C; Afshari, Ashkan; Nguyen, Lyly; Dortch, Richard D; Thayer, Wesley P

2018-06-01

Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device. The conduit-based device group was compared to a control group of rats that underwent a standard end-to-end microsurgical repair of the sciatic nerve. Animals underwent behavioral assessments at weekly intervals post-operatively using the sciatic functional index (SFI) test. Animals were sacrificed at four weeks to obtain motor axon counts from immunohistochemistry. A sub-group of animals were sacrificed immediately post repair to obtain MRI images. SFI scores were superior in rats which received conduit-based repairs compared to the control group. Motor axon counts distal to the injury in the device group at four weeks were statistically superior to the control group. MRI tractography was used to demonstrate repair of two nerves using the novel conduit device. A conduit-based nerve coaptation device avoids sutures at the nerve repair site and leads to improved outcomes in a rat model. Conduit-based nerve repair devices have the potential to standardize nerve repairs while improving outcomes.

[Biodegradable catheters for fistula prevention in hypospadias. Experimental preliminary study].

PubMed

Ramos, J L; Aldazabal, P; Zuza, E; Sarasúa, J R; Arrieta, A; Villanueva, A; Eizaguirre, I

2013-04-01

Continuous technical innovations are not enough to resolve the high incidence of fistula after hypospadias repair. A urethral catheter-tutor made of reabsorbable polymeric biomaterial (RPB) which could be left in situ long enough could reduce the complications. To investigate in an animal model differents RPB to be used in urology. CRL Wistar rats, males, divided into 5 equal groups according to the used polymers: polylactide; lactic-coprolactone copolymer; lactic-glycolic copolymer; simulated; control silicones. Three individuals were sacrificed per group at 4th, 10th and 16th week. In all animals (exceptuating the simulated group), biomaterial was fixed to the bladder wall bylaparotomy. Animals remained in individual housing and kept under daily control of hematuria during the first 15 days and weekly weight and urine control for pH and lactate. After being slaughtered, remaining polymer was collected for chemical analysis and bladder tissue for hystologic study. There was no mortality, hematuria nor other clinical signs. The bladder wall showed a mild foreign body reaction. The values of lactate and pH in urine did not reach toxic levels. Lactic-glycolic was totally reabsorbed by the 10th week and had the lowest degree of calcification. Polylactide and lactic-coprolactone remained intact. The model of urinary bladder has proven useful for studying the degradation of bioresorbable polymers. The analyzed polymers have spent long time to be reabsorbed, so we will have to study new others.

Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

PubMed

Jessop, J J; Gale, K; Bayer, B M

1988-01-01

The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco

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

Lee, C.K.; Brown, B.G.; Reed, E.A.

A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSF from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg tar permore » week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the [sup 32]P-postlabeling method with the P[sub 1] nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC-treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic. 31 refs., 4 figs., 2 tabs.« less

Characterization of vascular complications in experimental model of fructose-induced metabolic syndrome.

PubMed

El-Bassossy, Hany M; Dsokey, Nora; Fahmy, Ahmed

2014-12-01

Vascular dysfunction is an important complication associated with metabolic syndrome (MS). Here we fully characterized vascular complications in a rat model of fructose-induced MS. MS was induced by adding fructose (10%) to drinking water to male Wistar rats of 6 weeks age. Blood pressure (BP) and isolated aorta responses phenylephrine (PE), KCl, acetylcholine (ACh), and sodium nitroprusside (SNP) were recorded after 6, 9, and 12 weeks of fructose administration. In addition, serum levels of glucose, insulin, uric acid, tumor necrosis factor α (TNFα), lipids, advanced glycation end products (AGEs), and arginase activity were determined. Furthermore, aortic reactive oxygen species (ROS) generation, hemeoxygenase-1 expression, and collagen deposition were examined. Fructose administration resulted in a significant hyperinslinemia after 6 weeks which continued for 12 weeks. It was also associated with a significant increase in BP after 6 weeks which was stable for 12 weeks. Aorta isolated from MS animals showed exaggerated contractility to PE and KCl and impaired relaxation to ACh compared with control after 6 weeks which were clearer at 12 weeks of fructose administration. In addition, MS animals showed significant increases in serum levels of lipids, uric acid, AGEs, TNFα, and arginase enzyme activity after 12 weeks of fructose administration. Furthermore, aortae isolated from MS animals were characterized by increased ROS generation and collagen deposition. In conclusion, adding fructose (10%) to drinking water produces a model of MS with vascular complications after 12 weeks that are characterized by insulin resistance, hypertension, disturbed vascular reactivity and structure, hyperuricemia, dyslipidemia, and low-grade inflammation.

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

PubMed

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

2018-04-01

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

The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles.

PubMed

Vatta, A F; Waller, P J; Githiori, J B; Medley, G F

2009-06-10

The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an "established" infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a "developing" infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1-6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden+/-standard deviation, SD: 23+/-33, 30+/-56 and 442+/-518 worms, P=0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens+/-SD: 1102+/-841, 649+/-855, 1051+/-661 worms, P=0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean+/-standard error of the mean, SEM, in ppm: 93.7+/-8.3; 101.5+/-8.3; 71.8+/-8.3, P=0.07) nor did they differ between the DEVGRP goats (mean+/-SEM, in ppm: 74.1+/-9.1; 75.4+/-9.1; 74.9+/-10.0, P>0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated.

Lack of resistance after re-exposure of cattle cured of Onchocerca ochengi infection with oxytetracycline.

PubMed

Nfon, Charles K; Makepeace, Benjamin L; Njongmeta, Leo M; Tanya, Vincent N; Trees, Alexander J

2007-01-01

Although vector control and ivermectin chemotherapy have led to a dramatic reduction in the incidence of river blindness (onchocerciasis), there is a consensus that additional control tools are required to sustain and extend this success. The recognition of endosymbiotic bacteria (Wolbachia) in filariae and their targeting by antibiotics constitutes the most significant and practicable opportunity for a macrofilaricidal therapy in the short-to-medium-term. Using Onchocerca ochengi in cattle, an analog of human onchocerciasis, we have previously shown that oxytetracycline is macrofilaricidal, and protective immunity exists naturally in a subset of animals termed putatively immune. Here, we report that although 24 weeks of weekly oxytetracycline treatment eliminated adult worms, cured animals remained susceptible to re-infection by natural challenge when compared with putatively immune cattle. However, their susceptibility was not significantly different from that of concurrently exposed, heavily infected animals. Thus, cattle cured by oxytetracycline are neither hypo-susceptible nor hyper-susceptible.

Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

PubMed

Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

1999-01-28

Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines.

Effects of propylene glycol on the metabolic status and milk production of dairy buffaloes.

PubMed

Hussein, H A; Abdel-Raheem, S M; Abd-Allah, M; Senosy, W

2015-01-01

The study was designed to investigate the effects of drenching with propylene glycol (PG) on body condition, serum metabolites and milk production during the transition period of dairy buffaloes. Animals were randomly allocated to a control group (n=5) and a PG group of 10 buffaloes that were drenched with 500 ml of propylene glycol once daily from 10 (9±3) days prepartum until 2 weeks postpartum. Ultrasound measurements of backfat thickness (BFT) were performed weekly, while blood samples were taken at -4, -2, 2, 4, 6, and 8 weeks from parturition for estimation of hematological and biochemical metabolites. At -4, -3, and -2 weeks from calving, BFT did not differ between the two groups, but decreased after calving and was higher for the control group than the PG group at weeks -1 and 1. Hematological analysis revealed insignificant changes between the two groups. Serum concentrations of non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose did not differ between the two groups before parturition. At 2 and 4 weeks from parturition, NEFA was higher for the control group than the PG group. Serum concentrations of BHBA were higher at 2, 4, 6, and 8 weeks in control animals than in treated buffaloes. In contrast, the glucose level was significantly increased in PG group when compared to the control group at week 2 postpartum (p<0.05). Serum concentrations of total cholesterol, triglycerides, total proteins, albumin, and globulins did not differ significantly between the two groups (p>0.05). Serum enzyme activities of aspartate aminotransferase and γ-glutamyl transferase were significantly higher in the control than in the PG group. In treated buffaloes significantly (p<0.05) higher average 60-day milk yields were recorded (8.4±0.22 vs. 10.7±0.40 kg/day). Milk composition did not differ between the two groups. Drenching of dairy buffaloes with propylene glycol may reduce the risk of ketosis, improve the metabolic status, and increase the milk yield.

Monitoring the healing process of rat bones using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Gamulin, O.; Serec, K.; Bilić, V.; Balarin, M.; Kosović, M.; Drmić, D.; Brčić, L.; Seiwerth, S.; Sikirić, P.

2013-07-01

The healing effect of BPC 157 on rat femoral head osteonecrosis was monitored by Raman spectroscopy. Three groups of rats were defined: an injured group treated with BPC 157 (10 μg/kg/daily ip), an injured control group (treated with saline, 5 ml/kg/daily ip), and an uninjured healthy group. The spectra were recorded and the healing effect assessed on samples harvested from animals which were sacrificed 3 and 6 weeks after being injured. The statistical analysis of the recorded spectra showed statistical differences between the BPC 157-treated, control, and healthy groups of animals. In particular, after 6 weeks the spectral resemblance between the healthy and BPC 157 samples indicated a positive BPC 157 influence on the healing process of rat femoral head.

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.

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

PubMed

Ahmed, Jawad Hassan; Abdulmajeed, Isra Mohammed

2017-01-01

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

Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats

PubMed Central

Chen, S.; Xie, W.; Strong, J. A.; Jiang, J.; Zhang, J.-M.

2015-01-01

Background Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. Methods We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. Results The uterine grafts survived and developed fluid filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first two weeks after the surgery, peaked at 2 to 5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviors. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fiber recording showed increased spontaneous activity, especially of C fibers, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibers, was observed in the adjacent sciatic nerve as well as in the uterine graft. Conclusions This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models. PMID:26688332

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

PubMed Central

Gómez-Clavel, José-Francisco; Gaitán-Cepeda, Luis-Alberto

2017-01-01

Background Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Material and Methods Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson’s trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. Results At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. Conclusions The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models. Key words:Bisphosphonates, osteonecrosis, dental extractions, animal model, BRONJ. PMID:28160593

Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

PubMed

Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

2016-03-01

Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

PubMed

Goyal, S; Manivannan, B; Ansari, A S; Jain, S C; Lohiya, N K

2010-02-03

The manuscript is one of the series of attempts in authenticating scientific documentation of the seeds of Carica papaya being traditionally used for contraception. To establish safety of the methanol sub-fraction (MSF) of the seeds of Carica papaya as a male contraceptive following long term oral treatment. MSF was administered orally to albino rats at multiples of contraceptive dose (CD) at 50 (1x), 100 (2x), 250 (5x) and 500 (10x)mg/kg body weight daily for 52 weeks. Body weight, organs weight, morbidity, mortality, clinical chemistry, sperm analysis, histopathology and serum testosterone were evaluated to assess the safety and contraceptive efficacy. MSF treatment at various dose regimens, daily for 52 weeks did not show significant changes in body weight, organs weight, food and water intake and pre-terminal deaths compared to those of control animals. Sperm count and viability in 50mg/kg body weight treated animals and the weight of epididymis, seminal vesicle and prostate of all the treated animals showed significant reduction compared to control. Cauda epididymal spermatozoa of 50mg/kg body weight treated animals were immotile. Azoospermia was observed in 100, 250 and 500 mg/kg body weight treated animals. Serum clinical parameters, serum testosterone and histopathology of vital organs were comparable to those of control animals. Histology of testis revealed adverse effects on the process of spermatogenesis, while the histology of epididymis, seminal vesicles and ventral prostate showed no changes compared to control. The long term daily oral administration of MSF affects sperm parameters without adverse side effects and is clinically safe as a male contraceptive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Effects of adrenalectomy and constant light on the rat estrous cycle.

PubMed

Hoffmann, J C

1978-01-01

Adult female ARS/Sprague-Dawley rats were allowed to acclimatize to a a lighting schedule of 12L:12D (LD) for 5 weeks. At that time, half the animals were adrenalectomized, and all rats remained in LD for an additional 4 to 5 weeks. Subsequently, half of the control and half of the adrenalectomized rats were exposed to constant light (LL) for an additional 8 weeks, at which time all animals were sacificed. Operated rats with regenerated adrenal tissue, determined either by macroscopic examination or serum corticosterone assay (about 50% of the rats), were excluded from all data calculations. Acute disturbances of estrous cycle length were minor. The long-term effects revealed a significant increase in 5-day cycles among the adrenalectomized rats, although the majority of cycles recorded (80%) were still 4 days in length. None of the rats in LD showed spontaneous persistent estrus. Adrenalectomy did not affect the number of ova shed. When placed in LL, the adrenalectomized rats continued to cycle longer than the unoperated controls, but all rats showed persistent estrus (5 or more consecutive days of vaginal cornification) within 7--8 weeks. Adrenalectomized rats had significantly higher body weights than controls. Relative uterine weight was decreased in these animals in both lighting regimens but only reached statistical significance in LD. Ovarian weight, by contrast, was significantly increased among adrenalectomized rats in LD but was identical in both groups in LL. Adrenal weight of intact rats was not altered by LL. Since estrous cycles can continue for at least 6 months in the absence of the adrenal gland, the persistent estrus that occurs in LL is not merely due to the loss of a diurnal rhythm of corticosteroids. Indeed, when adrenalectomized rats are placed in LL, they continue to show estrous cycles longer than do intact rats. Adrenalectomy does appear to increase the length of the cycle in some animals, and the hormonal basis for this warrants further study.

Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice.

PubMed

Tabrizian, Kaveh; Yazdani, Abdolmajid; Baheri, Behnam; Payandemehr, Borna; Sanati, Mehdi; Hashemzaei, Mahmoud; Miri, Abdolhossein; Zandkarimi, Majid; Belaran, Maryam; Fanoudi, Sahar; Sharifzadeh, Mohammad

2016-01-01

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

Newly designed "pieced" stent in a rabbit model of benign esophageal stricture.

PubMed

Liu, Jin; Shang, Liang; Liu, Ji-Yong; Qin, Cheng-Yong

2015-07-28

To investigate a newly designed stent and its dilatation effect in a rabbit model of benign esophageal stricture. Thirty-four New Zealand white rabbits underwent a corrosive injury in the middle esophagus for esophageal stricture formation. Thirty rabbits with a successful formation of esophageal strictures were randomly allocated into two groups. The control group (n = 15) was implanted with a conventional stent, and the study group (n = 15) was implanted with a detachable "pieced" stent. The study stent (30 mm in length, 10 mm in diameter) was composed of three covered metallic pieces connected by surgical suture lines. The stent was collapsed by pulling the suture lines out of the mesh. Two weeks after stricture formation, endoscopic placement of a conventional stent or the new stent was performed. Endoscopic extraction was carried out four weeks later. The extraction rate, ease of extraction, migration, complications, and survival were evaluated. Stent migration occurred in 3/15 (20%) animals in the control group and 2/15 (13%) animals in the study group; the difference between the two groups was not statistically significant. At the end of four weeks, the remaining stents were successfully extracted with the endoscope in 100% (11/11) of the animals in the study group, and 60% (6/10) of the animals in the control group; this difference was statistically significant (P < 0.05). There was no difference in the mean number of follow-up days between the control and study groups (25.33 vs 25.85). Minor bleeding was reported in five cases in the study group and four in the control group. There were no severe complications directly associated with stent implantation or extraction in either of the two groups. In this experimental protocol of benign esophageal strictures, the novel "pieced" stent demonstrated a superior removal rate with a similar migration rate compared to a conventional stent.

Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

PubMed

Padilha, Gisele de A; Horta, Lucas F B; Moraes, Lillian; Braga, Cassia L; Oliveira, Milena V; Santos, Cíntia L; Ramos, Isalira P; Morales, Marcelo M; Capelozzi, Vera Luiza; Goldenberg, Regina C S; de Abreu, Marcelo Gama; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

2016-12-01

In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed. Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04). In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study

PubMed Central

Singh, Ravijot; Chauhan, Vijendra; Chauhan, Neena; Sharma, Sansar

2009-01-01

Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at 48 weeks showed columnar orientation. The control side showed no changes over the shaved off articular surface in all the rabbits. One rabbit at 4 weeks had a dislocation of the patella on the control side. None of the rabbits developed any infection or wound dehiscence. Conclusion: Autologous periosteal graft transplantation can be a promising substitute for articular cartilaginous defects. PMID:19838382

The Effect of Root Coating with Titanium on Prevention of Root Resorption in Avulsed Teeth: An Animal Study

PubMed Central

Heydari, Azar; Tahmasbi, Soodeh; Badiee, Mohammadreza; Izadi, SeyedSadra; Mashhadi Abbas, Fatemeh; Mokhtari, Sepideh

2016-01-01

Introduction: Tooth avulsion is a real dental emergency. If immediate replantation is not performed, the avulsed tooth may be lost due to inflammatory or replacement resorption. This animal study aimed to evaluate the bone response to the titanium coating of the root surface as an artificial barrier, and prevention of resorption of avulsed teeth. Methods and Materials: This experimental study was conducted on four male dogs. The dogs were randomly divided into two groups for assessment at two and eight weeks. Four teeth were extracted in each animal. The root surfaces of the test group were coated with a titanium layer using the Electron Beam Deposition system. After 24 h, replantation of the teeth was performed. Two animals were sacrificed after two weeks and the remaining dogs were killed after eight weeks. The presence of inflammation, inflammatory resorption, replacement resorption, periodontal regeneration, periapical granuloma and ankylosis were evaluated through histological analyses. Results: Inflammatory root resorption was not present in any tooth except one tooth in the coated group after eight weeks. Replacement resorption was noted just in three of the non-coated teeth after two weeks and two teeth after eight weeks. The McNemar's test revealed that the frequency of replacement resorption in the non-coated group was significantly higher than the coated group (P=0.031). Conclusion: Based on the results of this study, it seems that coating the root surfaces of avulsed teeth with titanium may control the replacement root resorption. PMID:27790261

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

PubMed

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

2002-07-01

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

Endothelial Arginine Resynthesis Contributes to the Maintenance of Vasomotor Function in Male Diabetic Mice

PubMed Central

Chennupati, Ramesh; Meens, Merlijn J. P. M. T.; Marion, Vincent; Janssen, Ben J.; Lamers, Wouter H.; De Mey, Jo G. R.; Köhler, S. Eleonore

2014-01-01

Aim Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. Methods and Results Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/− = Ass-KOTie2) were generated by crossing Assfl/fl mice ( = control) with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP) was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively) in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO) were significantly reduced when compared to diabetic control mice. Conclusions Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes. PMID:25033204

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

PubMed

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

2002-03-01

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

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

Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures.

PubMed

Schwerin, Susan C; Hutchinson, Elizabeth B; Radomski, Kryslaine L; Ngalula, Kapinga P; Pierpaoli, Carlo M; Juliano, Sharon L

2017-06-15

Although rodent TBI studies provide valuable information regarding the effects of injury and recovery, an animal model with neuroanatomical characteristics closer to humans may provide a more meaningful basis for clinical translation. The ferret has a high white/gray matter ratio, gyrencephalic neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to behavioral training, have a body size compatible with pre-clinical MRI, and are cost-effective. We optimized the surgical procedure for controlled cortical impact (CCI) using 9 adult male ferrets. We used subject-specific brain/skull morphometric data from anatomical MRIs to overcome across-subject variability for lesion placement. We also reflected the temporalis muscle, closed the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and immunohistochemical data from 6 additional animals using the optimized surgical protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week) and 1 moderately injured animal surviving sixteen weeks. The optimized surgical protocol resulted in consistent injury placement. Astrocytic reactivity increased with injury severity showing progressively greater numbers of astrocytes within the white matter. The density and morphological changes of microglia amplified with injury severity or time after injury. Motor and cognitive impairments scaled with injury severity. The optimized surgical methods differ from those used in the rodent, and are integral to success using a ferret model. We optimized ferret CCI surgery for consistent injury placement. The ferret is an excellent animal model to investigate pathophysiological and behavioral changes associated with TBI. Published by Elsevier B.V.

Mouse spermatogonia exposed to a high, multiply fractionated dose of a cancer chemotherapeutic drug: mutation analysis by electrophoresis.

PubMed

Johnson, F M; Lewis, S E

1981-04-01

Male mice of the DBA/2J strain were injected with procarbazine at a dose of 200 mg/kg body weight twice weekly until an accumulated dose of 2400 mg/kg was reached. A concurrent control group, injected only with the vehicle (saline) was also established. Most of the treated animals died as a result of exposure and all survivors became temporarily sterile. After regaining fertility the few survivors were repeatedly mated with C57BL/6J females over several weeks time to generate a population of F1 animals. The parental animals and the F1 were subsequently analyzed by electrophoresis for the occurrence of newly arisen mutations of spermatogonial origin. A mutation in the gene Pep-3 was found.

Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice.

PubMed

Bidinotto, Lucas T; Costa, Celso A R A; Salvadori, Daisy M F; Costa, Mirtes; Rodrigues, Maria A M; Barbisan, Luís F

2011-08-01

This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P < 0.01) leukocyte DNA damage than its respective positive group exposed to MNU alone at week 3. In the medium-term study, DDB-initiated mice were allocated into three groups: vehicle group (positive control) and LGEO 125 or 500 mg kg⁻¹ (five times per week for 6 weeks; test groups). At week 20, all animals were euthanized and mammary glands, colon and urinary bladder were processed for histopathological analyses for detection of preneoplastic and neoplastic lesions. A slight non-significant effect of treatment with LGEO 500 mg kg⁻¹ in reducing development of alveolar and ductal mammary hyperplasia was found (P = 0.075). Our findings indicate that lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice. Copyright © 2010 John Wiley & Sons, Ltd.

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.

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

PubMed

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

2017-05-23

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

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

PubMed

Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

2011-01-01

Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Recovery from impaired muscle growth arises from prolonged postnatal accretion of myonuclei in Atrx mutant mice

PubMed Central

Yan, Keqin; Price-O’Dea, Tina

2017-01-01

Reduced muscle mass due to pathological development can occur through several mechanisms, including the loss or reduced proliferation of muscle stem cells. Muscle-specific ablation of the α-thalassemia mental retardation syndrome mutant protein, Atrx, in transgenic mice results in animals with a severely reduced muscle mass at three weeks of age; yet this muscle mass reduction resolves by adult age. Here, we explore the cellular mechanism underlying this effect. Analysis of Atrx mutant mice included testing for grip strength and rotorod performance. Muscle fiber length, fiber volume and numbers of myofiber-associated nuclei were determined from individual EDL or soleus myofibers isolated at three, five, or eight weeks. Myofibers from three week old Atrx mutant mice are smaller with fewer myofiber-associated nuclei and reduced volume compared to control animals, despite similar fiber numbers. Nonetheless, the grip strength of Atrx mutant mice was comparable to control mice when adjusted for body weight. Myofiber volume remained smaller at five weeks, becoming comparable to controls by 8 weeks of age. Concomitantly, increased numbers of myofiber-associated nuclei and Ki67+ myoblasts indicated that the recovery of muscle mass likely arises from the prolonged accretion of new myonuclei. This suggests that under disease conditions the muscle satellite stem cell niche can remain in a prolonged active state, allowing for the addition of a minimum number of myonuclei required to achieve a normal muscle size. PMID:29095838

Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.

PubMed

Vidal-Gutiérrez, X; Gómez-Clavel, J-F; Gaitán-Cepeda, L-A

2017-03-01

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson's trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models.

Effect of nicotinic acid on the sleep time and tolerance induced by ethanol in the rat

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

Basilio, C.; Toro, A.; Yojay, L.

The intraperitoneal (i.p.) administration (50 mg/kg) of nicotinic acid (NA), markedly decreased the sleep time of rats pretreated (10 min before), post-treated (10 min after) or simultaneously treated with ethanol (4 g/Kg i.p.). A similar effect was observed on the sleep time induced by pentobarbital (37 mg/Kg i.p.). Blood alcohol levels (BAL) were the same or slightly higher in the animals pretreated with NA than in the control animals pre-injected with saline. Nicotinamide and NAD had no effect. A total of three doses of ethanol, each one administered weekly or biweekly, induced tolerance, which persisted for approximately six weeks. Aftermore » this period, a hypersensitivity to ethanol appeared to develop. This phenomenon was not observed when NA was pre-injected 10 min before each dose of ethanol. The sleep time of the latter animals did not change neither during the treatment period nor after six weeks without any treatment. BAL were slightly higher in NA treated than in control animals. The authors concluded that the effect of NA on the sleep time and tolerance induced by ethanol is not due to an increased rate of its metabolism and/or elimination but to a long-lasting effect that decreases the sensitivity of the nervous cells to ethanol. The mechanisms involved in the shortening of the sleep time as well as those responsible for the loss of the capacity to develop tolerance are under current investigation.« less

Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier--curcumin.

PubMed

Alizadeh, Ali Mohammad; Khaniki, Mahmood; Azizian, Saleh; Mohaghgheghi, Mohammad Ali; Sadeghizadeh, Majid; Najafi, Farhood

2012-08-15

Curcumin is a potential natural anticancer drug with limited bioavailability due to the lack of solubility in aqueous solvents. The present study is designed to investigate the preventive effects of polymeric nanocarrier-curcumin (PNCC) on colon carcinogenesis in an azoxymethane-induced rat tumor. Forty rats were divided into control, curcumin- and PNCC-treated groups. Animals received azoxymethane (AOM) as a carcinogenic agent (15 mg/kg, s.c.) weekly for two consecutive weeks. They were given curcumin 0.2% and PNCC two weeks before till 14 weeks after the last injection of AOM. In the end, post euthanasia, the entire gastrointestinal tract was scrutinized for tumors, and the rest of the body for metastatic deposits. Tumor number, size and location were characterized. The histopathological and immunohistochemistry examinations were also performed on colon tissue. In vivo, curcumin nanoparticles inhibited colon cancer growth in animal model. The tumors incidence and number decreased by nanocurcumin comparison with control. Furthermore, the nuclear/cytoplasmic ratio, epithelial stratification, nuclear dispolarity, goblet depletion, structural abnormality, and the expression of Beta-catenin and Bcl-2 proteins were reduced in PNCC compared to others groups (P<0.05). In addition, Bax protein expression was significantly increased in PNCC in comparison with control and curcumin-treated groups (P<0.001). The present study demonstrated the potential anticancer effects of PNCC in a typical animal model. The results provide evidence that nanopolymeric curcumin exerts a significant chemopreventive effect on AOM-initiated colon cancer through cell proliferation inhibition and apoptosis induction. More investigations are needed to confirm its safety for human use. Copyright © 2012 Elsevier B.V. All rights reserved.

High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

PubMed

Chang, Seo-Na; Han, Juhee; Abdelkader, Tamer Said; Kim, Tae-Hyoun; Lee, Ji Min; Song, Juha; Kim, Kyung-Sul; Park, Jong-Hwan; Park, Jae-Hak

2014-09-01

Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress. We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels. Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells. © 2014 Wiley Periodicals, Inc.

p53 and Bcl-2expression in response to boldenone induced liver cells injury.

PubMed

Tousson, Ehab; Alm-Eldeen, Abeer; El-Moghazy, Mostafa

2011-09-01

Boldenone is an anabolic steroid developed for veterinary use. Recently, it is used by bodybuilders in both off-season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. So, the present study was designed to investigate the possible effect of using growth promoter boldenone undecylenate on the rabbit liver tissue. Thirty-two adult New Zealand rabbits were divided into four groups (8 animals each). Control group includes animals that injected intramuscularly with olive oil and dissected after 3 weeks. The experimental groups include animals that receive one, two and three intramuscular injections of 5 mg/kg body weight boldenone, respectively. The animals were dissected after 3, 6 and 9 weeks respectively, where the interval of each dose of boldenon was 3 weeks. Small pieces of the liver tissues were sent for the histopathological examination. Apoptotic p53 and antiapoptotic Bc1-2 proteins were localized immunohistochemically. Histological observations of the liver tissue showed that the sinusoidal congestion was the most prominent feature that extended from the centrilobular to the periportal regions. Hepatocellular vacuolation in the centrilobular region was also detected. Liver immunohistochemical observation showed a significant increase of the apoptotic protein p53 and a significant decrease in the antiapoptotic Bc1-2 proteins. The highest frequency of p53 positive cells was observed in the liver sections of three dose of boldenone injections, while the lowest in control group, also the highest frequency of Bcl-2 positive cells was observed in the liver sections of control group while the lowest in three dose of boldenone injections. The present results investigate that people should be careful if they want to use such steroids to enhance their strength and endurance.

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.

Does Telomere Shortening Precede the Onset of Hypertension in Spontaneously Hypertensive Mice?

PubMed

Chiu, Christine L; Hearn, Nerissa L; Paine, Devin; Steiner, Nicole; Lind, Joanne M

2016-10-01

Telomere length is widely considered as a marker of biological aging. Clinical studies have reported associations between reduced telomere length and hypertension. The aim of this study was to compare telomere length in hypertensive and normotensive mice at pre-disease and established disease time points to determine whether telomere length differs between the strains before and after the onset of disease. Genomic DNA was extracted from kidney and heart tissues of 4-, 12-, and 20-week-old male hypertensive (BPH/2J) and normotensive (BPN/3J) mice. Relative telomere length (T/S) was measured using quantitative PCR. Age was inversely correlated with telomere length in both strains. In 4-week-old pre-hypertensive animals, no difference in T/S was observed between BPH/2J and BPN/3J animals in kidney or heart tissue (kidney p = 0.14, heart p = 0.06). Once the animals had established disease, at 12 and 20 weeks, BPH/2J mice had significantly shorter telomeres when compared to their age-matched controls in both kidney (12 weeks p < 0.001 and 20 weeks p = 0.004) and heart tissues (12 weeks p < 0.001 and 20 weeks p < 0.001). This is the first study to show that differences in telomere lengths between BPH/2J and BPN/3J mice occur after the development of hypertension and do not cause hypertension in the BPH/2J mice.

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat.

PubMed

El-Tahry, H; Marei, H; Shams, A; El-Shahat, M; Abdelaziz, H; Abd El-Kader, M

2016-06-01

Demyelination was induced by two weeks cuprizone treatment. Rats of +ve control and triiodothyronine (T3) then received three subcutaneous injections of either saline or T3 day after day and sacrificed at the end of the third and fifth weeks. Animals in -ve control group received only standard rodent chow. After one week of cuprizone withdrawal the corpus callosum in +ve control and T3 treated rats was still demyelinated as revealed by MBP immunohistochemistry. The assay of PLP gene showed significant increase of T3 treated group compared to both the -ve control and +ve control groups. After three weeks, significant improvement in myelination was detected in T3-treated group compared to +ve control as detected by both MBP immunohistochemistry and electron microscopy. After one week of cuprizone withdrawal, PDGFRα positive cells and gene expression showed significant increase in +ve control and T3-treated groups as compared to -ve control with insignificant difference in between the former two groups. After three weeks of cuprizone withdrawal, PDGFRα positive cells in T3-treated and +ve control groups decreased to the control levels. These results suggest that T3 was effective in improving remyelination when administered during acute phase and might direct progenitor lineage toward oligodendrocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.

PubMed

Lambert, C S; Philpot, R M; Engberg, M E; Johns, B E; Wecker, L

2015-09-15

Studies have demonstrated that administration of the neuronal nicotinic receptor agonist varenicline to rats with olivocerebellar lesions attenuates balance deficits on a rotorod and balance beam, but the effects of this drug on gait deficits have not been investigated. To accomplish this, male Sprague-Dawley rats were trained to walk on a motorized treadmill at 25 and 35 cm/s and baseline performance determined; both temporal and spatial gait parameters were analyzed. A principal component analysis (PCA) was used to identify the key components of gait, and the cumulative gait index (CGI) was calculated, representing deviations from prototypical gait patterns. Subsequently, animals either remained as non-lesioned controls or received injections of 3-acetylpyridine (3-AP)/nicotinamide to destroy the climbing fibers innervating Purkinje cells. The gait of the non-lesioned group was assessed weekly to monitor changes in the normal population, while the gait of the lesioned group was assessed 1 week following 3-AP administration, and weekly following the daily administration of saline or varenicline (0.3, 1.0, or 3.0mg free base/kg) for 2 weeks. Non-lesioned animals exhibited a 60-70% increased CGI over time due to increases in temporal gait measures, whereas lesioned animals exhibited a nearly 3-fold increased CGI as a consequence of increases in spatial measures. Following 2 weeks of treatment with the highest dose of varenicline (3.0mg free base/kg), the swing duration of lesioned animals normalized, and stride duration, stride length and step angle in this population did not differ from the non-lesioned population. Thus, varenicline enabled animals to compensate for their impairments and rectify the timing of the gait cycle. Copyright © 2015 Elsevier B.V. All rights reserved.

Persistence of Viral Reservoirs in Multiple Tissues after Antiretroviral Therapy Suppression in a Macaque RT-SHIV Model

PubMed Central

Franks, Tamera; Kiser, Rebecca; Coalter, Vicky; Smedley, Jeremy; Piatak, Michael; Mellors, John W.; Lifson, Jeffrey D.; Ambrose, Zandrea

2013-01-01

Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood. PMID:24367650

Hydroethanolic extract of Psidium guajava leaf for induced osteoarthritis using a guinea pig model.

PubMed

Tanideh, N; Zare, Z; Jamshidzadeh, A; Lotfi, M; Azarpira, Negar; Sepehrimanesh, M; Koohi-Hosseinabadi, O

2017-01-01

We investigated the therapeutic effects of an extract of Psidium guajava (guava) leaf on experimentally induced osteoarthritis in guinea pig. The left knee of 30 male guinea pigs was anesthetized and the cranial cruciate ligament was severed. The animals were followed for 8 weeks until osteoarthritis was confirmed by radiography and histopathology. Animals were divided randomly into five groups; group 1, the ligament was severed and untreated; group 2, the ligament was severed and treated with piascledine, an extract of soybean and avocado; group 3, the ligament was severed and treated with 200 mg/kg hydroethanolic extract of guava; group 4, the ligament was severed and treated with 400 mg/kg hydroethanolic extract of guava; and group 5, control animals without surgery or extracts. Radiological and histopathological evaluations after 8 weeks showed reduced severity of osteoarthritis in the piascledine treatment group compared to group 1. The guava extract also reduce the severity of osteoarthritis compared to controls. Histopathological examination of treatment and control groups showed that treatment the guava extract improved lesions significantly. Hydroethanolic extracts of guava leaf appears to prevent osteoarthritis by inhibition of free radical formation in the knee joint.

Treatment of dermatophytosis in dogs and cats: review of published studies.

PubMed

Moriello, Karen A

2004-04-01

The recent literature on the treatment of dermatophytosis in dogs and cats was reviewed. Based upon in vitro studies using isolated infected hairs and controlled or field in vivo studies, the following topical treatments were consistently found to be antifungal (i.e. antidermatophyte): lime sulfur (1:16), 0.2% enilconazole rinses, and a combined 2% miconazole/chlorhexidine shampoo. Animals or hairs were either bathed or rinsed once or twice weekly. Itraconazole, griseofulvin and terbinafine were evaluated in controlled or field studies, most commonly involving cats. Griseofulvin (50 mg kg(-1)) was reported to cure infected animals in 41-70 days. Itraconazole (10 mg kg(-1) once daily or in a combined daily/pulse therapy 10 mg kg(-1) once daily for 28 days and then week on/week off) was reported to cure infected animals in 56-70 days. Low-dose itraconazole (1.5-3.0 mg kg(-1)) in 15-day cycles required 1-3 cycles (15-45 days). Various doses of terbinafine (5-40 mg kg(-1)) were reportedly used to treat dogs or cats. The higher doses of terbinafine (> 20 mg kg(-1)) were required to achieve a mycological cure; the number of treatment days to cure varied from 21 to > 126 days. Lufenuron was reported anecdotally to be an effective cure, however, this was not substantiated in controlled studies. Finally, fungal vaccines were not found to be effective against challenge exposure, however, there is evidence that they may be useful in treatment protocols.

Omega-3 Fatty Acids Attenuate Brain Alterations in High-Fat Diet-Induced Obesity Model.

PubMed

de Mello, Aline Haas; Schraiber, Rosiane de Bona; Goldim, Mariana Pereira de Souza; Garcez, Michelle Lima; Gomes, Maria Luiza; de Bem Silveira, Gustavo; Zaccaron, Rubya Pereira; Schuck, Patrícia Fernanda; Budni, Josiane; Silveira, Paulo Cesar Lock; Petronilho, Fabricia; Rezin, Gislaine Tezza

2018-05-04

This study evaluated the effects of omega-3 on inflammation, oxidative stress, and energy metabolism parameters in the brain of mice subjected to high-fat diet-induced obesity model. Body weight and visceral fat weight were evaluated as well. Male Swiss mice were divided into control (purified low-fat diet) and obese (purified high-fat diet). After 6 weeks, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + OMEGA-3. Fish oil (400 mg/kg/day) or saline solution was administrated orally, during 4 weeks. When the experiment completed 10 weeks, the animals were euthanized and the brain and visceral fat were removed. The brain structures (hypothalamus, hippocampus, prefrontal cortex, and striatum) were isolated. Treatment with omega-3 had no effect on body weight, but reduced the visceral fat. Obese animals showed increased inflammation, increased oxidative damage, decreased antioxidant enzymes activity and levels, changes in the Krebs cycle enzyme activities, and inhibition of mitochondrial respiratory chain complexes in the brain structures. Omega-3 treatment partially reversed the changes in the inflammatory and in the oxidative damage parameters and attenuated the alterations in the antioxidant defense and in the energy metabolism (Krebs cycle and mitochondrial respiratory chain). Omega-3 had a beneficial effect on the brain of obese animals, as it partially reversed the changes caused by the consumption of a high-fat diet and consequent obesity. Our results support studies that indicate omega-3 may contribute to obesity treatment.

The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats

PubMed Central

2013-01-01

Background Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze.Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Results Results showed that prenatal and postnatal TRF supplementation increased the brain (4–6 fold increase) and plasma α-tocotrienol (0.8 fold increase) levels in male off-springs. There is also notably better cognitive performance based on the Morris water maze test among these male off-springs. Conclusion Based on these results, it is concluded that prenatal and postnatal TRF supplementation improved cognitive function development in male progeny rats. PMID:23902378

The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats.

PubMed

Nagapan, Gowri; Meng Goh, Yong; Shameha Abdul Razak, Intan; Nesaretnam, Kalanithi; Ebrahimi, Mahdi

2013-07-31

Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Results showed that prenatal and postnatal TRF supplementation increased the brain (4-6 fold increase) and plasma α-tocotrienol (0.8 fold increase) levels in male off-springs. There is also notably better cognitive performance based on the Morris water maze test among these male off-springs. Based on these results, it is concluded that prenatal and postnatal TRF supplementation improved cognitive function development in male progeny rats.

Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep.

PubMed

Fernández-Sarmiento, J Andrés; Domínguez, Juan M; Granados, María M; Morgaz, Juan; Navarrete, Rocío; Carrillo, José M; Gómez-Villamandos, Rafael J; Muñoz-Rascón, Pilar; Martín de Las Mulas, Juana; Millán, Yolanda; García-Balletbó, Montserrat; Cugat, Ramón

2013-02-06

The use of plasma rich in growth factors (PRGF) has been proposed to improve the healing of Achilles tendon injuries, but there is debate about the effectiveness of this therapy. The objective of the present study was to evaluate the histological effects of PRGF, which is a type of leukocyte-poor platelet-rich plasma, on tendon healing. The Achilles tendons of twenty-eight sheep were divided surgically. The animals were randomly divided into four groups of seven animals each. The repaired tendons in two groups received an infiltration of PRGF intraoperatively and every week for the following three weeks under ultrasound guidance. The tendons in the other two groups received injections with saline solution. The animals in one PRGF group and one saline solution group were killed at four weeks, and the animals in the remaining two groups were killed at eight weeks. The Achilles tendons were examined histologically, and the morphometry of fibroblast nuclei was calculated. The fibroblast nuclei of the PRGF-treated tendons were more elongated and more parallel to the tendon axis than the fibroblast nuclei of the tendons in the saline solution group at eight weeks. PRGF-treated tendons showed more packed and better oriented collagen bundles at both four and eight weeks. In addition to increased maturation of the collagen structure, fibroblast density was significantly lower in PRGF-infiltrated tendons. PRGF-treated tendons exhibited faster vascular regression than tendons in the control groups, as demonstrated by a lower vascular density at eight weeks. PRGF was associated with histological changes consistent with an accelerated early healing process in repaired Achilles tendons in sheep after experimental surgical disruption. PRGF-treated tendons showed improvements in the morphometric features of fibroblast nuclei, suggesting a more advanced stage of healing. At eight weeks, histological examination revealed more mature organization of collagen bundles, lower vascular densities, and decreased fibroblast densities in PRGF-treated tendons than in tendons infiltrated with saline solution. These findings were consistent with a more advanced stage of the healing process. Based on the findings in this animal model, PRGF infiltration may improve the early healing process of surgically repaired Achilles tendons.

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.

Disturbed Cartilage and Joint Homeostasis Resulting From a Loss of Mitogen-Inducible Gene 6 in a Mouse Model of Joint Dysfunction

PubMed Central

Pest, Michael A.; Russell, Bailey A.; Zhang, Yu-Wen; Jeong, Jae-Wook; Beier, Frank

2017-01-01

Objective Mitogen-inducible gene 6 (MIG-6) regulates epidermal growth factor receptor (EGFR) signaling in synovial joint tissues. Whole-body knockout of the Mig6 gene in mice has been shown to induce osteoarthritis and joint degeneration. To evaluate the role of chondrocytes in this process, Mig6 was conditionally deleted from Col2a1-expressing cell types in the cartilage of mice. Methods Bone and cartilage in the synovial joints of cartilage-specific Mig6-deleted (knockout [KO]) mice and control littermates were compared. Histologic staining and immunohistochemical analyses were used to evaluate joint pathology as well as the expression of key extracellular matrix and regulatory proteins. Calcified tissue in synovial joints was assessed by micro–computed tomography (micro-CT) and whole-skeleton staining. Results Formation of long bones was found to be normal in KO animals. Cartilage thickness and proteoglycan staining of articular cartilage in the knee joints of 12-week-old KO mice were increased as compared to controls, with higher cellularity throughout the tissue. Radiopaque chondro-osseous nodules appeared in the knees of KO animals by 12 weeks of age and progressed to calcified bone–like tissue by 36 weeks of age. Nodules were also observed in the spine of 36-week-old animals. Erosion of bone at ligament entheses was evident by 12 weeks of age, by both histologic and micro-CT assessment. Conclusion MIG-6 expression in chondrocytes is important for the maintenance of cartilage and joint homeostasis. Dysregulation of EGFR signaling in chondrocytes results in anabolic activity in cartilage, but erosion of ligament entheses and the formation of ectopic chondro-osseous nodules severely disturb joint physiology. PMID:24966136

Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

PubMed

Zhang, S; Chu, W C; Lai, R C; Lim, S K; Hui, J H P; Toh, W S

2016-12-01

Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 μg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Living Animals in the Classroom: A Meta-Analysis on Learning Outcome and a Treatment-Control Study Focusing on Knowledge and Motivation

NASA Astrophysics Data System (ADS)

Hummel, Eberhard; Randler, Christoph

2012-02-01

Prior research states that the use of living animals in the classroom leads to a higher knowledge but those previous studies have methodological and statistical problems. We applied a meta-analysis and developed a treatment-control study in a middle school classroom. The treatments (film vs. living animal) differed only by the presence of the living animal. Both treatments were based on the self-determination theory. More than 400 pupils filled in pre-test, post-test and two follow-up-tests (with a delay of 6-8 weeks and 7-8 months). After each lesson, pupils rated the lesson on a short intrinsic motivation scale. In the meta-analysis, we found that the living animal treatments significantly scored better than a control group, but not when comparing living animals with alternative treatments. In the treatment-control study, both treatments led to a significant increase in knowledge but there were no differences between film and living animal treatment. Pre-test and previous grading had a significant influence on post- and both follow-up tests. In the mouse lesson, pupils of the living animal group showed higher values in interest and competence and lower values in pressure. Interest and competence correlated positively with achievement, while pressure correlated negatively.

Effect of chronic mitral valve damage on activity of pulmonary rapidly adapting receptors in the rabbit

PubMed Central

Gunawardena, S; Bravo, E; Kappagoda, C T

1998-01-01

The effects of acute pulmonary venous congestion on the activity of rapidly adapting receptors (RARs) were determined in intact (control and sham-operated) rabbits and in rabbits 6 and 12 weeks after surgical destruction of the mitral valve.Destruction of the mitral valve increased the mean left atrial pressure (LAP) by approximately 2·6 and 3·8 mmHg, 6 and 12 weeks after surgery, respectively. These changes were accompanied by significant increases in left ventricular weight. The effect of acute increments in LAP on RAR activity was examined against this background of chronic pulmonary venous congestion.In intact control and sham-operated animals RAR activity increased from 48·8 ± 0·9 to 83·5 ± 3·6 and 121·1 ± 4·7 action potentials min−1 when the LAP was raised by 5 and 10 mmHg, respectively, above control values. Six weeks after surgery only 40 % of RARs were activated in this way.In animals maintained for 12 weeks after surgery, RAR activity at LAPs of 6·6 ± 1·2 (control), 11·6 ± 1·2 and 16·6 ± 1·2 (mmHg) were 35·5 ± 2·3, 33·8 ± 14·4 and 34·0 ± 3·4 action potentials min−1, respectively. These changes were statistically not significant.Slowly adapting receptors (SARs) in the lung showed a small but statistically significant increase in activity when the left atrial pressure was acutely elevated in both intact and mitral valve damaged animals.It is concluded that chronic pulmonary venous congestion resulting from destruction of the mitral valve attenuates the ability of RARs to respond to acute moderate elevations of LAP. PMID:9679165

21 CFR 520.1120b - Haloxon boluses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... anthelmintic used in cattle for the control of gastrointestinal roundworms of the genera Haemonchus, Ostertagia... week of slaughter. (6) Do not treat dairy animals of breeding age or older. [40 FR 13838, Mar. 27, 1975...

Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

PubMed

Garcia, Carlos Eduardo de O; Araújo, Bruno C; Mello, Paulo H; Narcizo, Amanda de M; Rodrigues-Filho, Jandyr A; Medrado, Andreone T; Zampieri, Ricardo A; Floeter-Winter, Lucile M; Moreira, Renata Guimarães

2013-10-01

Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. Copyright © 2013 Elsevier Inc. All rights reserved.

Nootropic and anti-stress effects of rice bran oil in male rats.

PubMed

Mehdi, Bushra Jabeen; Tabassum, Saiqa; Haider, Saida; Perveen, Tahira; Nawaz, Amber; Haleem, Darakhshan Jabeen

2015-07-01

Rice bran oil (RBO) is an important product of rice bran. It is considered to be one of the most important nutritious oil due to its favorable fatty acid composition and unique composition of naturally occurring biologically active antioxidant compounds. This study was designed to monitor the effects of oral intake of RBO on stress response in rats. RBO was extracted using hexane. Rats were divided into Control and test (RBO-treated). RBO-treated rats were given 0.2 ml/day RBO for 6 weeks. Food intake and body weight changes were monitored weekly. After 6 weeks open field activity and Morris Water Maze (MWM) test were performed. Results showed that weekly cumulative food intake but not body weight were lower in RBO-treated rats during 1st to 5th week of treatment, which were normalized at the end of treatment. Exploratory activity of RBO-treated rats in an open field was increased. Spatial memory in Morris water maze was enhanced in RBO-treated than control rats. An episode of 2 h restraint stress decreased the 24 h food intake of both control and RBO-treated animals. Behavioral deficits were lower in RBO-treated rats. Exposure of 2 h restraint stress increased brain serotonin (5-hydroxytryptamine: 5-HT) metabolism. These increases were lower in RBO-treated restrained than their respective control animals. Serotonergic neurotransmitter mechanism is implicated in stress. The findings of the study show beneficial effects of RBO in learning and memory functions. Moreover, the study also highlights the attenuating effect of RBO on stress induced behavioral and neurochemical effects in rats.

Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.

PubMed

Tsuneyama, Koichi; Nishida, Takeshi; Baba, Hayato; Taira, Shu; Fujimoto, Makoto; Nomoto, Kazuhiro; Hayashi, Shinichi; Miwa, Shigeharu; Nakajima, Takahiko; Sutoh, Mitsuko; Oda, Emu; Hokao, Ryoji; Imura, Johji

2014-09-01

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG. MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed. The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH. DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

[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.

Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy

PubMed Central

Byrareddy, Siddappa N.; Arthos, James; Cicala, Claudia; Villinger, Francois; Ortiz, Kristina T.; Little, Dawn; Sidell, Neil; Kane, Maureen A.; Yu, Jianshi; Jones, Jace W.; Santangelo, Philip J.; Zurla, Chiara; McKinnon, Lyle R.; Arnold, Kelly B.; Woody, Caroline E.; Walter, Lutz; Roos, Christian; Noll, Angela; Van Ryk, Donald; Jelicic, Katija; Cimbro, Raffaello; Gumber, Sanjeev; Reid, Michelle D.; Adsay, Volkan; Amancha, Praveen K.; Mayne, Ann E.; Parslow, Tristram G.; Fauci, Anthony S.; Ansari, Aftab A.

2017-01-01

Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α4β7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4+ T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn. This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy. PMID:27738167

Effects of gravity on the circadian period in rats

NASA Technical Reports Server (NTRS)

Murakami, Dean M.; Demaria, Victor H.; Fuller, Charles A.

1991-01-01

The effect of increased gravity force on the circadian period of body temperature and activity of rats was investigated using rats implanted with a small radio telemetry device and, after a 2-week recovery and a 3-week control period at 1G, rotated at for 4 weeks at a constant 2G field in a 18-ft-diam centrifuge. Measurements of the mean freerunning period of the temperature and activity rhythms after 10 days showed that the exposure to 2G led to a functional separation of the pacemakers that regulate the activity and the temperature in the animals. Each pacemaker reacted differently: the activity period increased and the temperature period decreased. By the third or the fourth week, the activity and the temperature periods have returned to 1G control levels.

BP and Vascular Function Following Space Flight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Chapman, Justin; Xue, Hong; Dierickx, Jacqueline; Roullet, Chantal; Roullet, Jean-Baptiste; Phanouvong, Thongchanh; Watanabe, Mitsuaki; Otsuka, Keiichi;

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.

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.

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

PubMed

Chudasama, H P; Bhatt, P A

2009-11-01

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

Mesenchymal stem cells restore orientation and exploratory behavior of rats after brain injury.

PubMed

Sokolova, I B; Fedotova, O R; Tsikunov, S G; Polyntsev, D G

2011-05-01

We studied the effects of intravenous and intracerebral transplantation of MSC on restoration of orientation and exploratory behavior of Wistar-Kyoto rats after removal of the left motor cortex. Removal of the motor cortex led to a significant reduction of the number of behavioral acts in the open field test. Two weeks after removal of the motor cortex and intravenous transplantation, the animals were as inhibited as the controls, but during the next 10 weeks, the behavioral status of these rats remained unchanged, while controls exhibited further behavioral degradation. After injection of MSC into the brain, the behavior of rats with trauma did not change in comparison with intact rats over 10 weeks.

Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice.

PubMed

Synhaeve, Nicholas; Wade-Gueye, Ndéye Marième; Musilli, Stefania; Stefani, Johanna; Grandcolas, Line; Gruel, Gaëtan; Souidi, Maâmar; Dublineau, Isabelle; Bertho, Jean-Marc

2014-01-01

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were then continuously contaminated with (90) Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in (90) Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of (90) Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis. Copyright © 2012 John Wiley & Sons, Ltd.

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

PubMed

Boudène, C; Collas, E; Jenkins, C

1975-01-01

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

Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity

PubMed Central

Li, Xingxing; Li, Shuangyan; Zheng, Wenhui; Pan, Jian; Huang, Kunyu; Chen, Rong; Pan, Tonghe; Liao, Guorong; Chen, Zhongming; Zhou, Dongsheng; Shen, Wenwen; Zhou, Wenhua; Liu, Yu

2015-01-01

The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine. PMID:26112338

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

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

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

1982-03-01

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

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

PubMed Central

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

2015-01-01

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

Canine parvovirus type 2 vaccine protects against virulent challenge with type 2c virus.

PubMed

Spibey, N; Greenwood, N M; Sutton, D; Chalmers, W S K; Tarpey, I

2008-04-01

The ability of dogs vaccinated with a live attenuated CPV type 2 (Nobivac Intervet) vaccine to resist challenge with a current CPV2c isolate was investigated. Six SPF beagle dogs were given the minimum recommended course of vaccination, comprising a single inoculation of vaccine (Nobivac Lepto+Nobivac Pi) at 8-10 weeks of age followed 3 weeks later with a parvovirus vaccine in combination with distemper, adenovirus and parainfluenza virus (Nobivac DHPPi) and a repeat leptospirosis vaccine. Six control dogs were kept unvaccinated. All animals were challenged orally with a type 2c isolate of CPV and monitored for clinical signs, virus shedding, white blood cell fluctuations and serological responses. All vaccinated dogs were fully protected; showing no clinical signs nor shedding challenge virus in the faeces, in contrast to control animals, which displayed all the typical signs of infection with pathogenic CPV and shed challenge virus in the faeces.

Impact of dietary dairy polar lipids on lipid metabolism of mice fed a high-fat diet.

PubMed

Reis, Mariza G; Roy, Nicole C; Bermingham, Emma N; Ryan, Leigh; Bibiloni, Rodrigo; Young, Wayne; Krause, Lutz; Berger, Bernard; North, Mike; Stelwagen, Kerst; Reis, Marlon M

2013-03-20

The effect of milk polar lipids on lipid metabolism of liver, adipose tissue, and brain and on composition of intestinal microbiota was investigated. C57BL/6J mice were fed a high-fat diet (HFD) for 5 weeks, followed by 5 weeks with HFD without (control) or supplemented with total polar lipids (TPL), phospholipids (PL), or sphingolipids (SPL). Animals fed SPL showed a tendency for lower triglyceride synthesis (P = 0.058) in the liver, but not in adipose tissue. PL and TPL reduced de novo hepatic fatty acid biosynthesis. The ratio of palmitoleic to palmitic acid in the liver was lower for animals fed SPL or TPL compared to control. There was little effect of the supplementation on the cecal microbiota composition. In the brain, DHA (C22:6) content correlated negatively with tetracosanoic acid (C24:0) after TPL supplementation (-0.71, P = 0.02) but not in control (0.26, P = 0.44). Arachidonic acid (C20:4) was negatively correlated with C24:0 in both groups (TPL, -0.77, P = 0.008; control, -0.81, P = 0.003).

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

PubMed

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

2015-01-01

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

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Electrical stimulation and testosterone enhance recovery from recurrent laryngeal nerve crush.

PubMed

Monaco, Gina N; Brown, Todd J; Burgette, Ryan C; Fargo, Keith N; Akst, Lee M; Jones, Kathryn J; Foecking, Eileen M

2015-01-01

This study investigated the effects of a combinatorial treatment, consisting of a brief period of nerve electrical stimulation (ES) and systemic supraphysiologic testosterone, on functional recovery following a crush of the recurrent laryngeal nerve (RLN). Prospective, controlled animal study. After a crush of the left RLN, adult male Sprague-Dawley rats were divided into four treatment groups: 1) no treatment, 2) ES, 3) testosterone propionate (TP), and 4) ES + TP. Each group was subdivided into 1, 2, 3, or 4 weeks post-operative survival time points. Groups had an n of 4- 9. Recovery of vocal fold mobility (VFM) was assessed. Brief ES of the proximal nerve alone or in combination with TP accelerated the initiation of functional recovery. TP administration by itself also produced increased VFM scores compared to controls, but there were no statistical differences between the ES-treated and TP-treated animals. Treatment with brief ES alone was sufficient to decrease the time required to recover complete VFM. Animals with complete VFM were seen in treatment groups as early as 1 week following injury; in the untreated group, this was not observed until at least 3 weeks post-injury, translating into a 66% decrease in time to complete recovery. Brief ES, alone or in combination with TP, promise to be effective therapeutic interventions for promoting regeneration following RLN injury.

Stress-induced rise in serum anti-brain autoantibody levels in the rat.

PubMed

Andrejević, S; Bukilica, M; Dimitrijević, M; Laban, O; Radulovic, J; Kovacevic-Jovanovic, V; Stanojevic, S; Vasiljevic, T; Marković, B M

1997-02-01

Sera from Wistar rats subjected to different stress procedures were tested by ELISA for the presence of autoantibodies with specificity for neuron-specific enolase (NSE) and S100 protein that are preferentially localized in neurons and glia, respectively. Autoantibodies were present in sera of animals before exposure to stress, and raised with age. Anti-NSE and anti-S100 autoantibody levels were increased one day after termination of restraint (2 hours daily, 10 days) and electric tail shock (80 shocks daily, 19 days), and in fifth and tenth week of overcrowding stress. Differences between stressed and control animals were not present one month following restraint and electric tail shock and in twentieth week of overcrowding.

Laparoscopic Partial Nephrectomy With Potassium-titanyl-phosphate Laser Versus Conventional Laparoscopic Partial Nephrectomy: An Animal Randomized Controlled Trial.

PubMed

Rioja, Jorge; Morcillo, Esther; Novalbos, José P; Sánchez-Hurtado, Miguel A; Soria, Federico; Pérez-Duarte, Francisco; Díaz-Güemes Martín-Portugüés, Idoia; Laguna, Maria Pilar; Sánchez-Margallo, Francisco Miguel; Rodríguez-Rubio Cortadellas, Federico

2017-01-01

To explore the feasibility, safety, and short-term results of potassium-titanyl-phosphate (KTP) laser laparoscopic partial nephrectomy (KTP-LPN) vs conventional laparoscopic partial nephrectomy (C-LPN). Thirty large white female pigs were randomized to KTP-LPN or C-LPN. Laparoscopic radical right nephrectomy was performed, and an artificial renal tumor was placed in the left kidney in 3 locations. A week later, 15 pigs underwent C-LPN and 15 underwent KTP-LPN. All C-LPNs were performed with renal ischemia. A 120-W setting was used, without arterial clamping in the KTP-LPN group. Follow-up was done at day 1, week 3, and week 6. Retrograde pyelography was performed at 6 weeks, followed by animal sacrifice and necropsy. All KTP-LPNs were performed without hilar clamping. C-LPNs were performed with hilar clamping, closing of the collecting system, and renorraphy. In the KTP laser group, 2 pigs died due to urinary fistula in the first week after surgery. In the C-LPN group, 1 pig died due to myocardial infarction and another due to malignant hyperthermia. Hemoglobin and hematocrit recovery were lower at 6 weeks in the KTP-LPN group. Renal function 24 hours after surgery was worse in the KTP-LPN group but recovered at 3 weeks and 6 weeks. No differences were observed in surgical margins. The necropsy showed no differences. Limitations of the study are the impossibility to analyze the collecting tissue sealing by the KTP, and the potential renal toxicity of the KTP laser. Although KTP-LPN is feasible and safe in the animal model, further studies are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Metronidazole for the treatment of Tritrichomonas foetus in bulls.

PubMed

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

2017-04-14

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

[Histomorphological analyse of accelerating the fibrocartilage layer repair of patella-patellar tendon junction in rabbits by low intensity pulsed ultrasound stimulation].

PubMed

Zhang, Baoliang; Lü, Hongbin; Hu, Jianzhong; Xu, Daqi; Zhou, Jingyong; Wang, Ye

2013-08-01

To analyse the effect of low intensity pulsed ultrasound stimulation (LIPUS) on accelerating the fibrocartilage layer repair of patella-patellar tendon junction. A total of 60 mature female New Zealand white rabbits undergoing standard partial patellectomy were divided into 2 groups randomly. The control group was given comfort treatment and the treatment group was given LIPUS treatment starting from day 3 to the end of week 6 postoperatively. The scheduled time points of animal euthanization would be at week 6, week 12 and week 18 postoperatively. The patella-patellar tendon (PPT) complex would be harvested and cut into sections after decalcification for H&E staining, Safranine o/fast green staining. The thickness and gray value of fibrocartilage layer were analyzed by SANO Microscope Partner image analyzer. At week 6, week 12 and week 18 postoperatively, the fibrocartilage layer in the treatment group was significantly thicker than that in the control group (P<0.01), and the gray value of fibrocartilage layer was significantly smaller than that in the control group (P<0.01). LIPUS helps to accelerate the fibrocartilage layer repair of patella-patellar tendon junction in rabbit models.

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

Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

PubMed Central

Singh, M; Li, X M; Wang, H; McGee, J P; Zamb, T; Koff, W; Wang, C Y; O'Hagan, D T

1997-01-01

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization. PMID:9125552

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.

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

PubMed Central

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

2009-01-01

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

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

PubMed

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

2009-07-28

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

Effect of exercise intensity on cerebrospinal fluid interleukin-6 concentration during recovery from exhaustive exercise in rats.

PubMed

Kılıç, M; Ulusoy, Ö; Cırrık, S; Hindistan, I E; Ozkaya, Y Gül

2014-03-01

The purpose of this study was to investigate the possible role of moderate and strenuous swimming training on plasma and cerebrospinal fluid (CSF) IL-6 (interleukin-6) levels during recovery from exhaustive exercise in rats. Wistar rats were divided into three groups: sedentary control (C), moderately trained (MT) and strenuously trained (ST). MT rats underwent swimming exercise for one hour/day and 5 days/week for 8 weeks. Animals in the ST group began swimming with 1 h/day and swimming duration was progressively increased by 30 min/wk, reaching 2.5 h/day by week 4 and stayed constant for an additional 4 weeks. After all animals underwent an acute exhaustive swimming exercise, animals were divided into 3 groups, and decapitated immediately, 24 and 48 hours after exhaustion to obtain tissue samples. Muscle citrate synthase activity, plasma and CSF IL-6 levels were determined. The citrate synthase activity was found to be higher in MT and ST groups compared to the C group. Although plasma IL-6 levels were found unaltered among all groups, the CSF IL-6 concentration was found to be increased 24 hours after exhaustive exercise of the ST group. We conclude that exercise training intensity is an important factor determining cerebrospinal IL-6 concentration after exhaustive exercise.

MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols)

NASA Astrophysics Data System (ADS)

Khodanovich, M.; Glazacheva, V.; Pan, E.; Akulov, A.; Krutenkova, E.; Trusov, V.; Yarnykh, V.

2016-02-01

Multiple sclerosis is a neurological disorder with poorly understood pathogenic mechanisms and a lack of effective therapies. Therefore, the search for new MS treatments remains very important. This study was performed on a commonly used cuprizone animal model of multiple sclerosis. It evaluated the effect of a plant-derived substance called Ropren® (containing approximately 95% polyprenols or long-chain isoprenoid alcohols) on cuprizone- induced demyelination. The study was performed on 27 eight-week old male CD-1 mice. To induce demyelination mice were fed 0.5% cuprizone in the standard diet for 10 weeks. Ropren® was administered in one daily intraperitoneal injection (12mg/kg), beginning on the 6th week of the experiment. On the 11th week, the corpus callosum in the brain was evaluated in all animals using magnetic resonance imaging with an 11.7 T animal scanner using T2- weighted sequence. Cuprizone treatment successfully induced the model of demyelination with a significant decrease in the size of the corpus callosum compared with the control group (p<0.01). Mice treated with both cuprizone and Ropren® did not exhibit demyelination in the corpus callosum (p<0.01). This shows the positive effect of polyprenols on cuprizone-induced demyelination in mice.

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

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

PubMed

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

2018-05-08

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

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.

Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

PubMed

Gessner, D K; Most, E; Schlegel, G; Kupczyk, K; Schwarz, F J; Eder, K

2015-12-01

This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins via milk was also greater in cows of the CLA group than in cows of the control group (+36, 50 and 24% for retinol, α-tocopherol and γ-tocopherol, respectively, p < 0.05). In agreement with higher concentrations of tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

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

Early Activation of Growth Pathways in Mitral Leaflets Exposed to Aortic Regurgitation: New Insights from an Animal Model.

PubMed

Marsit, Ons; Royer, Olivier; Drolet, Marie-Claude; Arsenault, Marie; Couet, Jacques; Morin, Stéphane; Levine, Robert A; Pibarot, Philippe; Beaudoin, Jonathan

2017-05-01

Mitral leaflet enlargement in patients with chronic aortic regurgitation (AR) has been identified as an adaptive mechanism potentially able to prevent functional mitral regurgitation (FMR) in response to left ventricular (LV) dilatation. The timing of valve enlargement is not known, and the related mechanisms are largely unexplored. AR was induced in 58 rats, and another 54 were used as sham controls. Animals were euthanized at different time points after AR creation (48 h, one week, and three months), and AR severity, FMR and LV dilatation were assessed using echocardiography. Mitral valves were harvested to document the reactivation of embryonic growth pathways. AR animals had increased LV dimensions and mitral annulus size. No animal developed FMR. No change in leaflet length or thickness was seen at 48 h; however, anterior mitral leaflets were longer and thicker in AR animals at one week and three months. Molecular changes were present early (at 48 h and at one week), with positive staining for transforming growth factor-b1 (TGF-b1), Alpha-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2), which suggested active matrix remodeling. Increased gene expression for collagen 1, TGF-β1, α-SMA and MMP-2 was found in the mitral valve at 48 h and at one week, but after three months their expression had returned to normal. This model of AR induces active expansion and thickening of the mitral leaflets. Growth signals are expressed acutely, but not at three months, which suggests that most of this enlargement occurs at an early stage. The stimulation of valvular growth could represent a new strategy for the prevention of FMR.

Light and water are not simple conditions: fine tuning of animal housing in male C57BL/6 mice.

PubMed

Langgartner, Dominik; Foertsch, Sandra; Füchsl, Andrea M; Reber, Stefan O

2017-01-01

While animal housing conditions are highly controlled and standardized between different laboratories, there are still many subtle differences that unavoidably influence the host organisms and, consequently, interlaboratory reproducibility. Here, we investigated the physiological and immunological consequences between two light/dark cycle (LDC) lengths (14-h/10-h vs. 12-h/12-h LDC) and two commonly used forms of drinking water (acidified drinking water (AW) versus normal tap water (NW)) in single-housed (SH) mice. Our results indicate that SH mice bred under a 12-h/12-h LDC and NW at the supplier's facility showed increased basal morning plasma corticosterone (CORT) levels even 4 weeks after arrival at our animal facility employing a 14-h/10-h LDC and AW. This effect was even more pronounced two weeks after arrival and had abated after 8 weeks. In agreement, increased plasma adrenocorticotropic hormone (ACTH), adrenal in vitro ACTH sensitivity, as well as relative and absolute adrenal weight normalized during this 8-week exposure to the novel and unfamiliar 14-h/10-h LDC and AW. Employment of a 12-h/12-h LDC in our facility completely abrogated the CORT-elevating effects of the 14-h/10-h LDC, despite these animals drinking AW. When both the water and light conditions were matched to those at the supplier's facility, we observed a further reduction in adrenal weight, increased thymus weight, and decreased pro-inflammatory cytokine secretion of isolated and anti-CD3/28-stimulated mesenteric lymph node cells. In summary, our results indicate that prolonged alteration of both the light phase and drinking water represent severe and long-lasting stressors for laboratory rodents. These findings are of general interest for all scientists obtaining their experimental animals from conventional suppliers.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

PubMed Central

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

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

PubMed

Samarakkody, U K; Hutson, J M

1992-07-01

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

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.

An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis.

PubMed

Giannessi, Elisabetta; Coli, Alessandra; Stornelli, Maria Rita; Miragliotta, Vincenzo; Pirone, Andrea; Lenzi, Carla; Burchielli, Silvia; Vozzi, Giovanni; De Maria, Carmelo; Giorgetti, Margherita

2014-11-01

The aim of this study was to investigate the ability of suturable platelet-rich plasma (PRP) membrane to promote peripheral nerve regeneration after neurotmesis and neurorraphy. A total of 36 rats were used: 32 animals underwent surgery and were split in two groups. An interim sacrifice was performed at 6 weeks postsurgery and final sacrifice at 12 weeks; four animals did not sustain nerve injury and served as control. Clinical, electromyographic (EMG), gross, and histological changes were assessed. The EMG signal was evaluated for its amplitude and frequency spectrum. Number of regenerating fibers, their diameter, and myelin thickness were histologically analyzed. Both EMG parameters showed a significant (p < 0.05) effect of treatment at 6 and 12 weeks postsurgery. At 6 weeks, the fiber density was statistically different between treated and untreated animals with a higher observed density in treated nerves. No difference in fiber density was observed at 12 weeks postsurgery. The distribution of fiber diameters showed an effect at 12 weeks when only the sections of the nerves sutured with PRP showed fibers with diameters greater than 6 µm. Our data show that the application of a PRP fibrin membrane around the neurorraphy improves the nerve regeneration process in a rat sciatic nerve model. The use of PRP as a suturable membrane could perform an action not only as a source of bioactive proteins but also as a nerve guide to hold the scar reaction and thus improve axonal regeneration. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Adaptation to a blood pressure telemetry system revealed by measures of activity, agility and operant learning in mice.

PubMed

Popova, Anfisa; Tsvirkun, Darya; Dolgov, Oleg; Anokhin, Konstantin; Alberts, Jeffrey; Lagereva, Evgeniia; Custaud, Marc-Antoine; Gauquelin-Koch, Guillemette; Vinogradova, Olga; Andreev-Andrievskiy, Alexander

Implantable telemetry enables continuous monitoring of physiological functions in freely moving animals and can greatly complement pharmacological research. Despite its miniaturization, a sensor/transmitter constitutes 5% or more of a mouse's bodyweight. The aim of the present study was to evaluate whether factors related to the presence of a probe/transmitter influence the ambulatory activity, strength, agility, or operant, motivated behaviors of this small rodent. Adult male mice (C57BL/6N, 22-25g, 9-10weeks; implanted n=26, intact n=45) were evaluated during week-long tests, conducted three and eight weeks after surgical implantation of the PA-C10 blood pressure probe. An open field test, grip force measurement, Rotarod test were performed, followed by 7-day continuous monitoring of spontaneous wheel running activity and positively reinforced operant conditioning in an automated data collection system. An implanted blood pressure transmitter did not affect behavior of mice in the open field test, on the Rotarod or their grip force, compared to unoperated controls. Voluntary wheel running distance was reduced three, but not eight weeks after implantation. Three weeks after the surgery, performance in the positively reinforced operant conditioning in operated mice was slightly decreased compared to intact animals, while retention and acquisition of a 2nd, reversal-learning task eight weeks after the surgery were unaffected. We conclude that an implantable transmitter may have detectable effects in the first few weeks following implantation on some elements of mouse behavior. With sufficient recovery, mice perform comparably to unoperated controls in tests of strength, endurance, agility and learned operant behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Percutaneous intraportal application of adipose tissue-derived mesenchymal stem cells using a balloon occlusion catheter in a porcine model of liver fibrosis.

PubMed

Avritscher, Rony; Abdelsalam, Mohamed E; Javadi, Sanaz; Ensor, Joe; Wallace, Michael J; Alt, Eckhard; Madoff, David C; Vykoukal, Jody V

2013-12-01

To investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis. Transcatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals. MSCs were allowed to dwell for 10 minutes using prolonged balloon inflation. Five control animals received a sham injection of normal saline in a similar fashion. Hepatic venous pressure gradient (HVPG) was measured immediately before necropsy. Specimens from all accessible lobes were obtained with ultrasound-guided percutaneous 18-gauge biopsy 2 hours after cell application. All animals were euthanized within 4 weeks. Fluorescent microscopy was used to assess the presence and distribution of cells. Liver injury and fibrosis were successfully induced in all animals. MSCs (6-10 × 10(7)) were successfully delivered into the portal vein in the six experimental animals. Cell application was not associated with vascular complications. HVPG showed no instances of portal hypertension. GFP-expressing MSCs were visualized in biopsy specimens and were distributed primarily within the sinusoidal spaces; however, 4 weeks after implantation, MSCs could not be identified in histologic specimens. A percutaneous endovascular approach for cell delivery using a balloon occlusion catheter proved safe for intraportal MSC application in a large animal model of liver fibrosis. © 2013 SIR Published by SIR All rights reserved.

The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles

PubMed Central

Vatta, A.F.; Waller, P.J.; Githiori, J.B.; Medley, G.F.

2009-01-01

The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an “established” infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a “developing” infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1–6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden ± standard deviation, SD: 23 ± 33, 30 ± 56 and 442 ± 518 worms, P = 0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens ± SD: 1102 ± 841, 649 ± 855, 1051 ± 661 worms, P = 0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean ± standard error of the mean, SEM, in ppm: 93.7 ± 8.3; 101.5 ± 8.3; 71.8 ± 8.3, P = 0.07) nor did they differ between the DEVGRP goats (mean ± SEM, in ppm: 74.1 ± 9.1; 75.4 ± 9.1; 74.9 ± 10.0, P > 0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated. PMID:19346076

Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

PubMed

Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

2012-10-01

The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

Effects of crocin and voluntary exercise, alone or combined, on heart VEGF-A and HOMA-IR of HFD/STZ induced type 2 diabetic rats.

PubMed

Ghorbanzadeh, V; Mohammadi, M; Dariushnejad, H; Chodari, L; Mohaddes, G

2016-10-01

Hyperglycemia is the main risk factor for microvascular complications in type 2 diabetes. Crocin and voluntary exercise have anti-hyperglycemic effects in diabetes. In this research, we evaluated the effects of crocin and voluntary exercise alone or combined on glycemia control and heart level of VEGF-A. Animals were divided into eight groups as: control (con), diabetes (Dia), crocin (Cro), voluntary exercise (Exe), crocin and voluntary exercise (Cro-Exe), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Oral glucose tolerance test (OGTT) was performed on overnight fasted control, diabetic and treated rats after 8 weeks of treatment. Then, serum insulin and heart VEGF-A protein levels were measured. Crocin combined with voluntary exercise significantly decreased blood glucose levels (p < 0.001) and insulin resistance (HOMA-IR) (p < 0.001) compared to diabetic group. VEGF-A level was significantly (p < 0.01) lower in Dia group compared to control group. The combination of crocin and voluntary exercise significantly enhanced VEGF-A protein levels in Dia-Cro-Exe and Cro-Exe group compared to diabetic and control groups, respectively; p < 0.001 and p < 0.05. Crocin combined with voluntary exercise improved insulin resistance (HOMA-IR) and reduced glucose levels in diabetic rats. Since both crocin and voluntary exercise can increase VEGF-A protein expression in heart tissue, they probably are able to increase angiogenesis in diabetic animals.

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.

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

PubMed

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

2014-12-17

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

Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study.

PubMed

Lerner, Michael Z; Matsushita, Takashi; Lankford, Karen L; Radtke, Christine; Kocsis, Jeffery D; Young, Nwanmegha O

2014-11-01

Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Animal Research. Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

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.

Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage.

PubMed

Siebelt, Michiel; Groen, Harald C; Koelewijn, Stuart J; de Blois, Erik; Sandker, Marjan; Waarsing, Jan H; Müller, Cristina; van Osch, Gerjo J V M; de Jong, Marion; Weinans, Harrie

2014-01-29

Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced subchondral sclerosis, synovial macrophage activation, and osteophyte formation.

Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.

PubMed

Boucher, Yves; Moreau, Nathan; Mauborgne, Annie; Dieb, Wisam

2018-06-18

We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms. Copyright © 2018. Published by Elsevier Inc.

The effect of dietary vitamin E level on selenium status in rats.

PubMed

Fujihara, T; Orden, E A

2014-10-01

The effect of varying levels of dietary vitamin E on selenium status was determined using 40 Wistar rats with similar initial body weight. The rats were equally divided into four groups and fed the following dietary treatments (mg vitamin E/kg DM): 18 (control; C-diet), 0 (0E-diet), 9 (0.5E-diet) and 36 (2E-diet) for either 4-week (Phase 1) or 8-week (Phase 2) period. At the end of experiment, animals were slaughtered to measure vitamin E and selenium levels in the brain, liver, spleen, kidney, muscles and blood tissues. Dietary vitamin E levels did not affect feed and water intake and body weight. But whole-blood selenium concentration in rats fed 0E-diet was higher than in rats fed 2E-diet after 4 weeks. Selenium level in muscle, spleen and brain was also higher (p < 0.05) in rats fed the 0E-diet than in rats fed C-diet after 4 weeks of feeding. On the other hand, selenium level in the muscle was lower (p < 0.05) in rats fed 0.5E-diet than in those fed 0E-diet after 4 weeks of feeding, but not after 8 weeks of feeding. Increasing dietary vitamin E level directly influenced selenium content of the spleen and brain after 8 weeks of feeding 2E-diet. Moreover, the twofold increase in vitamin E intake resulted in a tendency to reduce whole-blood selenium level and total selenium in the liver and kidney after 4 and 8 weeks. The results showed that the increasing dietary vitamin E level resulted in a tendency to reduce Se contents in some vital organs of the body such as the liver and kidney, suggesting their close compensatory interrelationship. Therefore, dietary vitamin E level directly influenced selenium metabolism in the animal body. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Inhalation reproductive toxicology studies: Sperm morphology study of n-hexane in B6C3F1 mice: Final report

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

Mast, T.J.; Hackett, P.L.; Decker, J.R.

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate the epididymal sperm morphology of male B6D3F1 mice 5 weeks after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Two concurrent positive control groups of animals were injected intraperitoneally with either 200 or 250 mg/kg ethyl methanesulfonate, a known mutagen, once each day for 5 consecutive days. Themore » mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. During the fifth post-exposure week the animals were killed and examined for gross lesions of the reproductive tract and suspensions of the epididymal sperm were prepared for morphological evaluations. The appearance and behavior of the mice were unremarkable throughout the experiment and there were no deaths. No evidence of lesions in any organ was noted at sacrifice. Mean body weights of male mice exposed to n-hexane were not significantly different from those for the 0-ppM animals at any time during the study. Analyses of the sperm morphology data obtained 5 weeks post-exposure (the only time point examined) indicated that exposure of male mice to relatively high concentrations of n-hexane vapor for 5 days produced no significant effects on the morphology of sperm relative to that of the 0-ppM control group. 24 refs., 2 figs., 7 tabs.« less

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3

PubMed Central

de Rozières, Sohela; Swan, Christina H; Sheeter, Dennis A; Clingerman, Karen J; Lin, Ying-Chuan; Huitron-Resendiz, Salvador; Henriksen, Steven; Torbett, Bruce E; Elder, John H

2004-01-01

Background The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. Results Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p ≤ 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p ≤ 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. Conclusions The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection. PMID:15555065

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3.

PubMed

de Rozières, Sohela; Swan, Christina H; Sheeter, Dennis A; Clingerman, Karen J; Lin, Ying-Chuan; Huitron-Resendiz, Salvador; Henriksen, Steven; Torbett, Bruce E; Elder, John H

2004-11-19

The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p < or = 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p < or = 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection.

Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis.

PubMed

Silva, Paulo Goberlânio de Barros; Ferreira Junior, Antonio Ernando Carlos; Teófilo, Carolina Rodrigues; Barbosa, Maritza Cavalcante; Lima Júnior, Roberto César Pereira; Sousa, Fabrício Bitú; Mota, Mário Rogério Lima; Ribeiro, Ronaldo de Albuquerque; Alves, Ana Paula Negreiros Nunes

2015-09-01

To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA). Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach. All ZA doses showed a higher radiolucent area than the control (p<0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p<0.0001, r(2)=0.8073) and leucocytosis (p<0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p<0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p<0.0001). We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

PubMed Central

Noble, Emily E.; Mavanji, Vijayakumar; Little, Morgan R.; Billington, Charles J.; Kotz, Catherine M.; Wang, ChuanFeng

2014-01-01

Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. PMID:24755094

Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

PubMed

Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

2014-10-01

Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities

PubMed Central

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

Purpose: To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Methods: Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Results: Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. Conclusion: In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye. PMID:26425316

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities.

PubMed

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye.

Morphological changes in the liver and kidneys of rats subjected to terminal ileum exclusion during obstructive cholestasis.

PubMed

Costa, Evandro Luis de Oliveira; Azevedo, Geraldo Magela de; Petroianu, Andy

2014-06-01

To investigate the effects of ileal exclusion on hepatic and renal morphology in extra-hepatic cholestasis. Twenty four rats were distributed into three groups. Group 1 (control) underwent laparotomy and laparorrhaphy. The animals in groups 2 and 3 underwent hepatic duct ligature and kept in cholestasis for four weeks. After this period, the rats in groups 2 and 3 underwent internal biliary derivation. In Group 3, the last ten centimeters of the terminal ileum were by passed and excluded. Four weeks later, histological and biochemical analysis were performed in all animals of the three groups. In Group 1, no abnormalities regarding hepatic morphology were observed. All animals from groups 2 and 3 presented hepatic fibrosis. No difference was observed between the two groups. No morphological differences in renal histology could be identified among the three groups. There were differences in AST (p<0.05), ALT (p<0.05), direct bilirubin (p<0.05), ƔGT (p<0.05), urea (p<0.05) and creatinine (p<0.05) in Group 3 compared to control. The distal ileum exclusion had no influence upon the hepatic and renal morphological alterations, and biochemical liver and kidney tests have worsened.

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Equivalent Thumbnail image of Modeled Snow Water Equivalent Animate: Season --- Two weeks --- One Day Snow Depth Thumbnail image of Modeled Snow Depth Animate: Season --- Two weeks --- One Day Average Snowpack Temp Thumbnail image of Modeled Average Snowpack Temp Animate: Season --- Two weeks --- One Day SWE

Impact of eprinomectin on grazing behaviour and performance in dairy cattle with sub-clinical gastrointestinal nematode infections under continuous stocking management.

PubMed

Forbes, A B; Huckle, C A; Gibb, M J

2004-11-10

Forty spring-calving cows and heifers (20 of each) were allowed to acquire infection with gastrointestinal (GI) nematodes naturally during grazing. The control group (10 cows and 10 heifers) were compared with 20 similar animals treated with eprinomectin in order to evaluate the effect of GI nematodes on grazing behaviour, milk production, body condition score and live weight. The animals were paired according to parity and milk yield during the week prior to treatment, then within replicate pair randomly allocated to a different treatment group. The grazing area was sub-divided into 20 replicated paddocks of equivalent size and topography. Grazing pairs of either control or treated animals were randomly assigned to each paddock over the duration of the study (one pair per paddock). Grazing behaviour was recorded for both groups over a 10-day period commencing 4 days after treatment with eprinomectin. Milk yield was recorded daily and milk quality was recorded weekly. Live weight and body condition score were recorded on the day of allocation, the day of initial treatment and thereafter at weekly intervals until the end of the 4-week trial. Faecal samples were collected from each animal prior to, and after, allocation and submitted for counts of nematode eggs. Additional faecal samples were taken at the end of the study for culture and nematode identification. Individual faecal samples were also analysed for residual digestibility. Pasture samples for nematode larval counts were taken at the same time as faecal sampling. The parasitological results showed low levels of faecal nematode egg output throughout the study, with the heifers having higher counts than the cows. Faecal culture yielded species of Ostertagia, Cooperia, and Trichostrongylus. Pasture larval levels were very low throughout with no value exceeding 68 larvae/kg dry matter (DM) of herbage. There were significant (P < 0.05) effects of treatment on grazing time, eating time, total bites, total grazing jaw movements (TGJM), idling time and mean meal duration. Treated cows and heifers grazed for 47 and 50 min longer per day, respectively, than controls (P = 0.016). Mean meal duration was extended as a result of anthelmintic treatment by 11 and 38 min, in cows and heifers, respectively (P = 0.012). There were no significant (P > 0.05) treatment effects on ruminating time or residual faecal digestibility, but idling time was significantly reduced in both treated cows and heifers, by 50 and 110 min, respectively (P = 0.010). In the treated cattle, there was an increase in solids-corrected milk yield compared with the control cattle, which was significant (P < 0.05) in weeks 2 and 3 after treatment. The response was particularly marked in heifers, where the difference in yield between treated and controls was up to 2.35 kg/day. The differences in live weight gain and condition score over 28 days post-treatment were significant (P < 0.05) in both cows and heifers, in favour of the treated animals.

Development of a microcontroller-based automatic control system for the electrohydraulic total artificial heart.

PubMed

Kim, H C; Khanwilkar, P S; Bearnson, G B; Olsen, D B

1997-01-01

An automatic physiological control system for the actively filled, alternately pumped ventricles of the volumetrically coupled, electrohydraulic total artificial heart (EHTAH) was developed for long-term use. The automatic control system must ensure that the device: 1) maintains a physiological response of cardiac output, 2) compensates for an nonphysiological condition, and 3) is stable, reliable, and operates at a high power efficiency. The developed automatic control system met these requirements both in vitro, in week-long continuous mock circulation tests, and in vivo, in acute open-chested animals (calves). Satisfactory results were also obtained in a series of chronic animal experiments, including 21 days of continuous operation of the fully automatic control mode, and 138 days of operation in a manual mode, in a 159-day calf implant.

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

PubMed Central

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

2016-01-01

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

The effect of animation on learning action symbols by individuals with intellectual disabilities.

PubMed

Fujisawa, Kazuko; Inoue, Tomoyoshi; Yamana, Yuko; Hayashi, Humirhiro

2011-03-01

The purpose of the present study was to investigate whether participants with intellectual impairments could benefit from the movement associated with animated pictures while they were learning symbol names. Sixteen school students, whose linguistic-developmental age ranged from 38?91 months, participated in the experiment. They were taught 16 static visual symbols and the corresponding action words (naming task) in two sessions conducted one week apart. In the experimental condition, animation was employed to facilitate comprehension, whereas no animation was used in the control condition. Enhancement of learning was shown in the experimental condition, suggesting that the participants benefited from animated symbols. Furthermore, it was found that the lower the linguistic developmental age, the more effective the animated cue was in learning static visual symbols.

Sutureless liver repair and hemorrhage control using laser-mediated fusion of human albumin as a solder.

PubMed

Wadia, Y; Xie, H; Kajitani, M

2001-07-01

Major liver trauma has a high mortality because of immediate exsanguination and a delayed morbidity from septicemia, peritonitis, biliary fistulae, and delayed secondary hemorrhage. We evaluated laser soldering using liquid albumin for welding liver injuries. Fourteen lacerations (6 x 2 cm) and 13 nonanatomic resection injuries (raw surface, 8 x 2 cm) were repaired. An 805-nm laser was used to weld 53% liquid albumin-indocyanine green solder to the liver surface, reinforcing it by welding a free autologous omental scaffold. The animals were heparinized and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, 16 soldering repairs were evaluated acutely at 3 hours. Eleven animals were evaluated chronically, two at 2 weeks and nine at 4 weeks. All 27 laser mediated-liver repairs had minimal blood loss compared with the suture controls. No dehiscence, hemorrhage, or bile leakage was seen in any of the laser repairs after 3 hours. All 11 chronic repairs healed without complication. This modality effectively seals the liver surface, joins lacerations with minimal thermal injury, and works independently of the patient's coagulation status.

Postangioplasty restenosis followed with magnetic resonance imaging in an atherosclerotic rabbit model.

PubMed

Hänni, Mari; Leppänen, Olli; Smedby, Orjan

2012-01-01

Rationale and Objectives. Testing a quantitative, noninvasive method to assess postangioplasty vessel wall changes in an animal model. Material and Methods. Six New Zealand white rabbits were subjected to atherosclerotic injury, including cholesterol-enriched diet, deendothelialization, and percutaneous transluminal angioplasty (PTA) in the distal part of abdominal aorta (four weeks after deendothelialization). The animals were examined with a 1.5T MRI scanner at three times as follows: baseline (six weeks after diet start and two days after PTA) and four weeks and 10 weeks after-PTA. Inflow angiosequence (M2DI) and proton-density-weighted sequence (PDW) were performed to examine the aorta with axial slices. To identify the inner and outer vessel wall boundaries, a dynamic contour algorithm (Gradient Vector Flow Snakes) was applied to the images, followed by calculation of the vessel wall dimensions. The results were compared with histopathological analysis. Results. The wall thickness in the lesion was significantly higher than in the control region at 4 and 10 weeks, reflecting induction of experimentally created after-angioplasty lesion. At baseline, no significant difference between the two regions was present. Conclusions. It is possible to follow the development of vessel wall changes after-PTA with MRI in this rabbit model.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis

PubMed Central

2011-01-01

Introduction Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT). Methods Male Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection. Results Interestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes. Conclusions These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments. PMID:22185204

Bioassay of 4'-(chloroacetyl)-acetanilide for possible carcinogenicity.

PubMed

1979-01-01

A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice were killed at the end of the last week of compound administration, while rats were observed for 1 week after compound administration ceased. There were no significant positive associations between the concentration of 4'-(chloroacetyl)-acetanilide administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for males and females of both species, indicating that the concentrations of 4'-(chloroacetyl)-acetanilide administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in rats of either sex or in male mice indicated a significant positive association between compound administration and tumor incidence. Although there was a significant positive association between the concentration of the compound administered and the incidences of hepatocellular adenomas in female mice, the Fischer exact comparisons were not significant. Under the conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.

The effect of methamphetamine on an animal model of erectile function

PubMed Central

Tar, Moses T.; Martinez, Luis R.; Nosanchuk, Joshua D.; Davies, Kelvin P.

2014-01-01

In the U.S. methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine (2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)) i.p. daily for three weeks and erectile function compared to untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals the ICP/BP ratio following 4 and 6mA stimulation decreased by approximately 50% compared to untreated animals and erectile dysfunction was also reversed by tadalafil. Overall our data suggests that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report erectile dysfunction associated with therapeutics containing methamphetamine or amphetamine with PDE5i. PMID:24706617

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

PubMed

Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

2017-06-01

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Implantation of Neural Probes in the Brain Elicits Oxidative Stress

PubMed Central

Ereifej, Evon S.; Rial, Griffin M.; Hermann, John K.; Smith, Cara S.; Meade, Seth M.; Rayyan, Jacob M.; Chen, Keying; Feng, He; Capadona, Jeffrey R.

2018-01-01

Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp), and Stearoyl-Coenzyme A desaturase 1 (Scd1) were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1) relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage following microelectrode implantation. PMID:29487848

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

PubMed Central

Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure.

PubMed

Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ ( p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

Effect of animal-assisted interventions on depression, agitation and quality of life in nursing home residents suffering from cognitive impairment or dementia: a cluster randomized controlled trial.

PubMed

Olsen, Christine; Pedersen, Ingeborg; Bergland, Astrid; Enders-Slegers, Marie-José; Patil, Grete; Ihlebaek, Camilla

2016-12-01

The prevalence of neuropsychiatric symptoms in cognitively impaired nursing home residents is known to be very high, with depression and agitation being the most common symptoms. The possible effects of a 12-week intervention with animal-assisted activities (AAA) in nursing homes were studied. The primary outcomes related to depression, agitation and quality of life (QoL). A prospective, cluster randomized multicentre trial with a follow-up measurement 3 months after end of intervention was used. Inclusion criteria were men and women aged 65 years or older, with a diagnosis of dementia or having a cognitive deficit. Ten nursing homes were randomized to either AAA with a dog or a control group with treatment as usual. In total, 58 participants were recruited: 28 in the intervention group and 30 in the control group. The intervention consisted of a 30-min session with AAA twice weekly for 12 weeks in groups of three to six participants, led by a qualified dog handler. Norwegian versions of the Cornell Scale for Depression, the Brief Agitation Rating Scale and the Quality of Life in Late-stage Dementia scale were used. A significant effect on depression and QoL was found for participants with severe dementia at follow-up. For QoL, a significant effect of AAA was also found immediately after the intervention. No effects on agitation were found. Animal-assisted activities may have a positive effect on symptoms of depression and QoL in older people with dementia, especially those in a late stage. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

PubMed

Aldigier, J C; Cook, J; Delebassée, S; Guibert, F; Touchard, G; Juzan, M; Gualde, N

1992-10-01

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.

Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

PubMed Central

Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

2016-01-01

To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve, and B. infantis) and Lactobacillus (eg, L. helveticus, and L. rhamnosus), with doses between 109 and 1010 colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future. PMID:27413138

Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review.

PubMed

Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

2016-10-30

To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum , B. breve , and B. infantis ) and Lactobacillus (eg, L. helveticus , and L. rhamnosus ), with doses between 10⁸ and 10¹⁰ colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future.

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

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

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

1990-05-01

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

Schistosoma japonicum: An ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes

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

Shi, Y.E.; Jiang, C.F.; Han, J.J.

1990-07-01

Water buffaloes were vaccinated three times with 10,000 Schistosoma japonicum cercariae irradiated with ultraviolet (uv) light at a dose of 400 microW x min/cm2. The irradiation was performed with cheap, simple, and portable equipment in a rural area of Hubei Province (People's Republic of China). A challenge infection of 1000 untreated cercariae was given to six vaccinated and six naive control buffaloes, while two vaccinated animals were not challenged. The experiment was terminated 6 weeks after the challenge. Control animals had lost body weight and harbored a mean of 110 worms and 37 eggs per gram of liver. The vaccinatedmore » animals gained weight after the challenge and developed 89% resistance to infection with S. japonicum. Since schistosomiasis japonica is nowadays transmitted in China predominantly by domestic livestock, a uv-attenuated cercarial vaccine for bovines may contribute to the control of this disease.« less

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

NASA Astrophysics Data System (ADS)

Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

2013-08-01

Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

PubMed Central

Kasten, M.R.; Sunshine, M.D.; Secrist, E.S.; Horner, P.J.; Moritz, C.T.

2013-01-01

Objective Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation improved subsequent volitional control of paretic extremities following injury. Approach We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4–C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main Results Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promotes recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioral tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury. PMID:23715242

Effects of xylitol on blood glucose, glucose tolerance, serum insulin and lipid profile in a type 2 diabetes model of rats.

PubMed

Islam, Md Shahidul; Indrajit, Mitesh

2012-01-01

The present study was conducted to examine the antidiabetic effects of xylitol in a type 2 diabetes rat model. Six-week-old male Sprague-Dawley rats were randomly divided into 3 groups: normal control (NC), diabetic control (DBC) and xylitol (XYL). Diabetes was induced only in the DBC and XYL animal groups by feeding them a 10% fructose solution for 2 weeks followed by an injection (i.p.) of streptozotocin (40 mg/kg body weight). One week after the streptozotocin injection, the animals with a nonfasting blood glucose level of >300 mg/dl were considered to be diabetic. The XYL group was fed further with a 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 5 weeks of intervention, food and fluid intake, body weight, blood glucose, serum fructosamine and most of the serum lipids were significantly decreased, and serum insulin concentration and glucose tolerance ability was significantly increased in the XYL group compared to the DBC group. Liver weight, liver glycogen and serum triglycerides were not influenced by feeding with xylitol. The data of this study suggest that xylitol can be used not only as a sugar substitute but also as a supplement to antidiabetic food and other food products. Copyright © 2012 S. Karger AG, Basel.

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

PubMed

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

1988-01-01

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

Quantity and quality of guinea pig (cavia porcellus) spermatozoa after administration of methanol extract of bitter melon (momordica charantia) seed and depot medroxy progesterone acetate (DMPA)

NASA Astrophysics Data System (ADS)

Ilyas, Syafruddin; Hutahaean, Salomo; Nursal

2018-03-01

The discovery of male contraceptive drugs continues to be pursued, due to the few participation of men associated with the lack of contraceptive options for men. The combination of bitter melon seed methanol extract and DMPA are the options that currently apply to men. Therefore, the use of guinea pigs as experimental animals conducted research using experimental methods with complete randomized design (CRD). There are 4 control groups and 4 treatment groups. The first group, control group of dimethyl sulphoxide (DMSO) for 0 week (K0), The second one, bitter melon seed extract of 50 mg/100g Body Weight/day for 0 week (P0), the third one, control group of dimethyl sulfoxide (DMSO) for 4 weeks (K1), the fourth one, bitter melon seed extract of 50 mg/100g BW/day for 4 weeks + Depot medroxy Progesterone Acetate (P1), the fifth one, control group of dimethyl sulfoxide (DMSO) for 8 weeks (K2), the sixth one, bitter melon seed extract of 50 mg/100g BW/day for 8 weeks + DMPA (P2), the seventh one, control group of dimethyl sulfoxide (DMSO) for 12 weeks (K3), the eighth one, bitter melon seed extract of 50 mg/100g BW/day for 12 weeks + DMPA (P3). Methanol extract of bitter melon seed to decrease the quantity and quality of guinea pig spermatozoa decreased significantly, i.e. viability and normal morphology of spermatozoa (p<0.05).

Depigmentation with tert-butyl hydroquinone using black guinea pigs.

PubMed

Patrick, E; Juberg, D R; O'Donoghue, J; Maibach, H I

1999-01-01

tert-Butyl hydroquinone (TBHQ) has important and functional uses in consumer and commercial applications, some of which involve human exposure primarily through dermal contact. To assist in the safety evaluation of TBHQ, this study was conducted to determine whether TBHQ would produce changes in skin pigmentation after repeated dermal application to black guinea pigs. Hydroquinone (HQ) and hydroquinone monomethyl ether (HQMME) were used as positive controls. TBHQ and HQ were tested at concentrations of 0.1, 1.0 and 5.0%, while HQMME was tested at a concentration of 10.0%. Groups of five males and five females were dosed with TBHQ, HQ, or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. In addition, animals (five males, five females) treated with HQMME received 13 doses over a 3-week period. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% TBHQ and HQ were slightly to moderately irritating, while 0.1% of each of these test materials produced only weak irritant responses. No irritant responses to hydrophilic ointment were observed and HQMME produced weak irritant responses after 2 weeks. Neither 0.1% TBHQ nor HQ produced depigmentation, while 20% of animals dosed with 1.0% TBHQ and 30% of animals dosed with 1.0% HQ had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% TBHQ or HQ were depigmented at the treatment site at the final evaluation. HQMME produced complete depigmentation of the skin and hair in all animals. Hyperpigmentation of the treatment site was observed in 80-100% of animals in all groups (with the exception of HQMME-treated animals, treated for only 3 weeks), which may be attributable to the use of hydrophilic ointment as the vehicle, the application procedure, or simply clipping hair from the skin. Thus, this study showed that TBHQ causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%.

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.

Effects of chronic centrifugation on mice

NASA Technical Reports Server (NTRS)

Janer, L.; Duke, J.

1984-01-01

Previous studies have shown that exposure to excess gravity in vitro alters the developmental sequence in embryonic mouse limbs and palates (Duke, Janer and Campbell, 1984; Duke, 1983). The effects of excess gravity on in vivo mammalian development was investigated using a small animal centrifuge. Four-week old female mice exposed to excess gravities of 1.8-3.5 G for eight weeks weighed significantly less than controls. Mice were mated after five weeks of adaptation to excess G, and sacrificed either at gestational day 12 or 18. There were fewer pregnancies in the centrifuged group (4/36) than in controls (9/31), and crown rump lengths (CRL) of embryos developing in the centrifuge were less than CRLs of 1-G embryos. These results show that although immersed in amniotic fluid, embryos are responsive to Delta-G.

Immunologic studies of poisonous Anacardiaceae: I. Production of tolerance and desensitization to poison Ivy and oak urushiols using esterified urushiol derivatives in guinea pigs.

PubMed

Watson, E S; Murphy, J C; Wirth, P W; Waller, C W; Elsohly, M A

1981-03-01

The development of contact sensitivity to poison ivy urushiol in Hartley guinea pigs was inhibited by i.v. injection of the diacetate esters of poison ivy and oak urushiols into guinea pigs 2 weeks prior to attempted sensitization with homologous antigen. Immune tolerance to urushiols of poison ivy and oak developed in 80% or more of the treated animals and persisted for the duration of the study, 8 weeks. The tolerance was immunologically specific for urushiols since the tolerant animals were sensitizable to the unrelated sensitizer 2, 4-dinitrochlorobenzene. Guinea pigs already sensitive to urushiol were also desensitized or hyposensitizied by i.v. injection of urushiol acetates in successively increasing doses. After receiving the equivalent of 16 mg of poison ivy and oak urushiols in the acetate form over a period of 12 weeks, 54% of a group of guinea pigs were desensitized to poison ivy. all of the remaining 46% of the guinea pigs still sensitive to poison ivy were substantially hyposensitized (no longer responded to 1.5 or 0.80 microgram test doses of PDC). A control group of guinea pigs was not hyposensitized by injection of vehicle, and remained highly sensitive throughout the 15 week study. The majority of treated animals (less than 80%) were also hyposensitized to poison sumac and cashew nut shell liquid allergens.

Biocompatibility and Biocorrosion of Hydroxyapatite-Coated Magnesium Plate: Animal Experiment.

PubMed

Lim, Ho-Kyung; Byun, Soo-Hwan; Woo, Jae-Man; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Bong-Ju; Kim, Hyoun-Ee; Lee, Jung-Woo; Kim, Soung-Min; Lee, Jong-Ho

2017-09-30

Magnesium (Mg) has the advantage of being resorbed in vivo, but its resorption rate is difficult to control. With uncontrolled resorption, Magnesium as a bone fixation material has minimal clinical value. During resorption not only is the strength rapidly weakened, but rapid formation of metabolite also occurs. In order to overcome these disadvantages, hydroxyapatite (HA) surface coating of pure magnesium plate was attempted in this study. Magnesium plates were inserted above the frontal bone of Sprague-Dawley rats in both the control group (Bare-Mg group) and the experimental group (HA-Mg group). The presence of inflammation, infection, hydrogen gas formation, wound dehiscence, and/or plate exposure was observed, blood tests were performed, and the resorption rate and tensile strength of the retrieved metal plates were measured. The HA-Mg group showed no gas formation or plate exposure until week 12. However, the Bare-Mg group showed consistent gas formation and plate exposure beginning in week 2. WBC (White Blood Cell), BUN (Blood Urea Nitrogen), Creatinine, and serum magnesium concentration levels were within normal range in both groups. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) values, however, were above normal range in some animals of both groups. The HA-Mg group showed statistically significant advantage in resistance to degradation compared to the Bare-Mg group in weeks 2, 4, 6, 8, and 12. Degradation of HA-Mg plates proceeded after week 12. Coating magnesium plates with hydroxyapatite may be a viable method to maintain their strength long enough to allow bony healing and to control the resorption rate during the initial period.

Biocompatibility and Biocorrosion of Hydroxyapatite-Coated Magnesium Plate: Animal Experiment

PubMed Central

Woo, Jae-Man; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Hyoun-Ee; Lee, Jung-Woo; Lee, Jong-Ho

2017-01-01

Magnesium (Mg) has the advantage of being resorbed in vivo, but its resorption rate is difficult to control. With uncontrolled resorption, Magnesium as a bone fixation material has minimal clinical value. During resorption not only is the strength rapidly weakened, but rapid formation of metabolite also occurs. In order to overcome these disadvantages, hydroxyapatite (HA) surface coating of pure magnesium plate was attempted in this study. Magnesium plates were inserted above the frontal bone of Sprague-Dawley rats in both the control group (Bare-Mg group) and the experimental group (HA-Mg group). The presence of inflammation, infection, hydrogen gas formation, wound dehiscence, and/or plate exposure was observed, blood tests were performed, and the resorption rate and tensile strength of the retrieved metal plates were measured. The HA-Mg group showed no gas formation or plate exposure until week 12. However, the Bare-Mg group showed consistent gas formation and plate exposure beginning in week 2. WBC (White Blood Cell), BUN (Blood Urea Nitrogen), Creatinine, and serum magnesium concentration levels were within normal range in both groups. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) values, however, were above normal range in some animals of both groups. The HA-Mg group showed statistically significant advantage in resistance to degradation compared to the Bare-Mg group in weeks 2, 4, 6, 8, and 12. Degradation of HA-Mg plates proceeded after week 12. Coating magnesium plates with hydroxyapatite may be a viable method to maintain their strength long enough to allow bony healing and to control the resorption rate during the initial period. PMID:28973984

The M16 mouse: an outbred animal model of early onset polygenic obesity and diabesity.

PubMed

Allan, Mark F; Eisen, Eugene J; Pomp, Daniel

2004-09-01

To characterize the phenotypic consequences of long-term selective breeding for rapid weight gain, with an emphasis on obesity and obesity-induced diabetes (diabesity). M16 is the result of long-term selection for 3- to 6-week weight gain from an ICR base population. Experiment 1 characterized males from both lines for body weights (3, 6, and 8 weeks), feed (4 to 8 weeks) and H(2)O (6 to 8 weeks) consumption, and heat loss, body composition, and levels of several plasma proteins at 8 weeks of age. Experiment 2 characterized differences between lines for both sexes at three ages (6, 8, and 16 weeks) and fed two diets (high and normal fat). Body weight, composition, blood glucose, and plasma insulin and leptin levels were evaluated after an 8-hour fast. At all ages measured, M16 mice were heavier, fatter, hyperphagic, hyperinsulinemic, and hyperleptinemic relative to ICR. M16 males and females were hyperglycemic relative to ICR, with 56% and 22% higher fasted blood glucose levels at 8 weeks of age. M16 mice represent an outbred animal model to facilitate gene discovery and pathway regulation controlling early onset polygenic obesity and type 2 diabetic phenotypes. Phenotypes prevalent in the M16 model, with obesity and diabesity exhibited at a young age, closely mirror current trends in human populations.

Effect of healing time on bone-implant contact of orthodontic micro-implants: a histologic study.

PubMed

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability.

Effect of Healing Time on Bone-Implant Contact of Orthodontic Micro-Implants: A Histologic Study

PubMed Central

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability. PMID:25006463

Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats.

PubMed

McIlwrath, Sabrina L; Westlund, Karin N

2015-01-21

To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters (P < 0.05). Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls. Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls. Hypersensitivity was attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC, or nociceptin, the endogenous ligand for opioid-receptor-like 1 receptor. The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus.

Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats

PubMed Central

McIlwrath, Sabrina L; Westlund, Karin N

2015-01-01

AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters (P < 0.05). Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls. Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls. Hypersensitivity was attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC, or nociceptin, the endogenous ligand for opioid-receptor-like 1 receptor. CONCLUSION: The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus. PMID:25624717

Decreased sensitivity to thermal pain in rats bred for high anxiety-related behaviour is attenuated by citalopram or diazepam treatment.

PubMed

Jochum, Thomas; Boettger, Michael Karl; Wigger, Alexandra; Beiderbeck, Daniela; Neumann, Inga D; Landgraf, Rainer; Sauer, Heinrich; Bär, Karl-Jürgen

2007-10-01

Complex interactions between pain perception, anxiety and depressive symptoms have repeatedly been described. However, pathophysiological or biochemical mechanisms underlying the alterations of pain perception in patients suffering from anxiety or depression still remain a matter of debate. Thus, we aimed to perform an investigation on pain perception in an animal model of extremes in anxiety-related behaviour, which might provide a tool for future studies. Here, thermal pain thresholds were obtained from rats with a genetic predisposition to high anxiety-related behaviour (HAB), including signs of comorbid depression-like behaviour and from controls (low-anxiety rats (LAB); cross-bred HAB and LAB rats; Wistar rats). Furthermore, the effect of eight-week antidepressive treatment using citalopram and of short-term anxiolytic treatment with diazepam on pain-related behaviour was assessed. Simultaneously, anxiety-related behaviour was monitored. At baseline, HAB animals showed 35% higher thresholds for thermal pain than controls. These were normalized to control levels after eight weeks of continuous citalopram treatment paralleled by a reduction of anxiety-related behaviour, but also acutely after diazepam administration. Overall, thermal pain thresholds in HAB animals are shifted in a similar fashion as seen in patients suffering from major depressive disorder. Antidepressive, as well as anxiolytic treatments, attenuated these differences. As the relative importance of the factors anxiety and depression cannot be derived from this study with certainty, extending these investigations to additional animal models might represent a valuable tool for future investigations concerning the interrelations between anxiety, depression, and pain at a molecular level.

Uncultured undifferentiated adipose-derived nucleated cell fractions combined with inside-out artery graft accelerate sciatic nerve regeneration and functional recovery.

PubMed

Mohammadi, R; Asadollahi, A; Amini, K

2014-09-01

Effects of transplantation of adipose-derived nucleated cell fractions (ADNCs) on sciatic nerve regeneration were studied. A 10-mm sciatic nerve defect was bridged using artery graft filled with ADNCs. In control group, artery graft was filled with saline alone. Regenerated nerve fibres were studied for 12 weeks. In sham-operated group, sciatic nerve was only exposed and manipulated. Behavioural and functional studies confirmed faster recovery of regenerated axons in ADNCs transplanted animals than in control group (P<0.05). At the end of study period, animals in ADNCs transplanted group achieved a sciatic functional index (SFI) value of -31.6 ± -3.14, whereas in control group a value of -42.5 ± -3.7 was found. Gastrocnemius muscle mass in ADNCs transplanted animals was found to be significantly higher than that in control group (P=0.001). Morphometric indices of regenerated fibres showed the number and diameter of myelinated fibres to be significantly higher in ADNCs transplanted animals than in control group (P=0.001). On immunohistochemistry, there was more positive staining of S100 in the ADNCs transplanted animals than in control group. ADNCs transplantation into an artery graft could be considered a readily accessible technique that improves functional recovery of sciatic nerve. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

PubMed

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Euterpe oleracea (açai) modifies sterol metabolism and attenuates experimentally-induced atherosclerosis.

PubMed

Feio, Claudine A; Izar, Maria C; Ihara, Silvia S; Kasmas, Soraia H; Martins, Celma M; Feio, Max N; Maués, Luís A; Borges, Ney C; Moreno, Ronilson A; Póvoa, Rui M; Fonseca, Francisco A

2012-01-01

Euterpe Oleracea (açai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis. Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry. At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, β-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ β-sitosterol (p =0.006) ratios than controls. Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.

Skeletal mass change as a function of gravitational loading

NASA Technical Reports Server (NTRS)

Pace, N.; Smith, A. H.; Rahlmann, D. F.

1985-01-01

The hypothesis that increased loading on an animal by chronic centrifugation results in an increase in skeletal mass was tested, using metabolically mature hamsters, rats, guinea pigs, Dutch rabbits and New Zealand rabbits representing a body mass range from 0.15 to 3.8 kg. Groups of 12 male animals of each species were subjeted to 2.0 g for 6 weeks on a 2.74 radius centrifuge with one degree of freedom. Subsequently, six of the animals were killed to measure whole body composition, while the rest comprised the control group, recovering for four weeks at 1.0 g prior to composition analysis. Results show a significant increase in bone mineral mass at 2.0 g. These centrifuge experiment results were then compared with the results of the USSR Cosmos Biosatellite experiment, whereby five rats experienced osteoporosis after 18.5 days of weightlessness. The opposing nature of effects that occurred at 0 g and 2.0 g is indicated schematically of particular interest is the fact that the bone mineral mass of the Cosmos 1129 flight rats was 17 pct less than that of the 1.0 g controls; whereas the bone mineral mass of the centrifuge rats was 18 pct greater than that of their 1.0 g controls. It is concluded that the bone mineral mass of the rat is directly proportional to gravitational loading over the range of 0 g to 2.0 g.

Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

PubMed

Barbieri, Lucas R; Lourenço-Filho, Domingos D; Tavares, Elaine R; Carvalho, Priscila O; Gutierrez, Paulo S; Maranhão, Raul C; Stolf, Noedir A G

2017-08-01

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts. Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments. LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach to coronary allograft vasculopathy. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

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

Tang, Lili; Southern Yangtze University, Wuxi; Guan Hongxia

Modulation by lycopene of aflatoxin B{sub 1} (AFB{sub 1})-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB{sub 1} (250 {mu}g/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB{sub 1} (250 {mu}g/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB{sub 1} and greatly modulated AFB{sub 1} metabolism andmore » metabolic activation. Urinary excretion of AFB{sub 1} phase 1 metabolites, AFM{sub 1}, AFQ{sub 1}, and AFP{sub 1}, was significantly decreased in lycopene-treated animals. Formation of serum AFB{sub 1}-albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p < 0.05) to 67.7% on day 15 (p < 0.001). Lycopene intervention also significantly reduced formation of AFB{sub 1}-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p < 0.05). Levels of AFB{sub 1}-N {sup 7}-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB{sub 1}-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB{sub 1}-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.« less

Intervertebral disc adaptation to wedging deformation.

PubMed

Stokes, Ian A F; Aronsson, David D; Clark, Katherine C; Roemhildt, Maria L

2006-01-01

Although scoliosis includes wedge deformities of both vertebrae and discs, little is known about the causes of the discal changes, and whether they result from mechanical influences on growth and/or remodelling. An external apparatus attached to transvertebral pins applied compression and 15 degrees of angulation to each of two adjacent young rat caudal intervertebral discs for 5 weeks (four animals), or for 10 weeks (four animals). Each week, micro-CT scanning documented the in vivo discal wedging. After euthanasia, tail segments (three vertebrae and the 2 angulated discs) were excised and their flexibility was measured over a range of lateral bending. The angle of maximum flexibility was recorded. Then discs were fixed in situ (with the external apparatus in place) and sectioned for polarized light microscopy. The disc-wedging deformity averaged 15 degrees initially, it averaged 20 degrees after 5 weeks, and then reduced to 10 degrees (in 10 week animals). The lateral bending flexibility showed a distinct maximum at an average of 1.1 degrees from the in vivo position in the 5-week animals, indicating structural remodeling of the discs almost to the deformed geometry. The 10-week animals had maximum flexibility at 1.4 degrees from the in vivo position (no significant difference between 5 and 10-week animals.) Collagen crimp angles [Cassidy et al., Conn Tiss Res 1989, 23:75-88] were not significantly different between convex and concave sides, again suggesting that remodeling had occurred. In a mechanically induced scoliosis deformity in skeletally immature rats, the intervertebral discs underwent remodeling within 5 weeks. This indicates that this animal model is suitable for studying adaptive wedging changes in human scoliosis.

Comparison of packing material in an animal model of middle ear trauma.

PubMed

Perez, Enrique; Hachem, Ralph Abi; Carlton, Daniel; Bueno, Isabel; Vernon, Stephen; Van De Water, Thomas R; Angeli, Simon I

2016-01-01

To compare the performance of absorbable gelatin sponge (AGS) with polyurethane foam (PUF) as middle ear packing material after mucosal trauma. Using a randomized, controlled and blinded study design fifteen guinea pigs underwent middle ear surgery with mucosal trauma performed on both ears. One ear was packed with either PUF or AGS while the contralateral ear remained untreated and used as non-packed paired controls. Auditory brainstem response (ABR) thresholds were measured pre-operatively and repeated at 1, 2, and 6weeks postoperatively. Histological analysis of middle ear mucosa was done in each group to evaluate the inflammatory reaction and wound healing. Another eighteen animals underwent middle ear wounding and packing in one ear while the contralateral ear was left undisturbed as control. Twelve guinea pigs were euthanized at 2weeks postoperatively, and six were euthanized at 3days post-operatively. Mucosal samples were collected for analysis of TGF-β1 levels by enzyme-linked immunosorbent assay. ABR recordings demonstrate that threshold level changes from baseline were minor in PUF packed and control ears. Threshold levels were higher in the AGS packed ears compared with both control and PUF packed ears for low frequency stimuli. Histological analysis showed persistence of packing material at 6weeks postoperatively, inflammation, granulation tissue formation, foreign body reaction and neo-osteogenesis in both AGS and PUF groups. TGF-β1 protein levels did not differ between groups. PUF and AGS packing cause inflammation and neo-osteogenesis in the middle ear following wounding of the mucosa and packing. Copyright © 2016 Elsevier Inc. All rights reserved.

A prospective pilot study to evaluate an animated home-based physical exercise program as a treatment option for patients with rheumatoid arthritis.

PubMed

Zernicke, Jan; Kedor, Claudia; Müller, Angela; Burmester, Gerd-Rüdiger; Reißhauer, Anett; Feist, Eugen

2016-08-18

Physical exercises and physiotherapy are of great importance for maintenance of joint function in patients with rheumatoid arthritis (RA). However, many RA patients complain about problems to receive prescriptions or have a lack of access to physiotherapy. Recent reports have shown positive effects of the Wii game console on physical and psychosocial conditions of patients with other underlying diseases. The primary objectives of this prospective controlled pilot study were to investigate feasibility and patients' assessment using an animated home-based exercise program. This pilot study was conducted as a single-center, cross-over trial with two treatment arms over 24 weeks. Eligibility criteria included patients with RA reaching low disease activity under therapy with a biological disease modifying anti-rheumatic drug (bDMARD). After detailed instruction, 15 patients started with a conventional home-based physical exercise program and 15 patients began with a predefined animated exercise program by using the Wii game console for 12 weeks. Afterwards, patients were crossed-over to the other treatment arm for another period of 12 weeks. Multi-methodical assessments were performed by qualitative analysis of the interview-data as well as statistical analysis of functional tests and patient reported outcomes (PRO's). Evaluation of the interviews indicated feasibility and usefulness of the chosen animated home-based exercise program. Forefoot disabilities were identified as a main limiting factor for performing some of the animated exercises. After 12 weeks, both treatment arms showed improvement of functional tests without significant differences between groups: Overall muscle strength improved for a mean value of 10 Newton (+12 %) and the mean 6-min walk test (6-MWT) distance increased for 28 meters (+5 %). This study showed that an animated home-based exercise program by using a Wii game console was feasible and beneficial for RA patients. Compared to standard physical home exercises, similar effects were observed indicating that such an animated program might be an alternative supportive option for RA patients. ClinicalTrials.gov ID: NCT02658370 (19-Jan-2016).

Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

PubMed

Peterson, C A; Murphy, R J; Dupont-Versteegden, E E; Houlé, J D

2000-01-01

The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

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.

Reduced Ribosomal Protein S6 Phosphorylation following Progressive Resistance Exercise in Growing Adolescent Rats

PubMed Central

Hellyer, Nathan J.; Nokleby, Jessica J.; Thicke, Bethany M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

2011-01-01

The purpose of the present study was to investigate moderate intensity progressive resistance exercise (PRE) in growing adolescent rats and its effect on muscle hypertrophy (defined as an increase in fiber cross-sectional area). We hypothesized that in adolescent animals moderate intensity PRE would increase: 1) fiber cross-sectional area (CSA); 2) myosin heavy chain (MyHC) content; and 3) expression and phosphorylation of cell signaling molecules involved in translational regulation, compared to age-matched sedentary controls (SED). In the PRE group, three-week old male rats were trained to climb a vertical ladder as a mode of PRE training such that by 10 weeks, all animals in the PRE group had progressed to carry an additional 80% of body weight per climb. In agreement with our hypotheses, we observed that 10 weeks of moderate PRE in adolescent animals was sufficient to increase CSA of muscle fibers and increase MyHC content. Average muscle fiber CSA increased by greater than 10% and total MyHC content increased by 35% (p<0.05) in the PRE group compared to SED animals. Concurrently, we investigated sustained changes in the expression and phosphorylation of key signaling molecules that are previously identified regulators of hypertrophy in adult animal models. Contrary to our hypotheses, expression and phosphorylation of the translational regulators mTOR and Akt were not increased in the PRE group. In addition, we observed that the ratio of phosphorylated-to-unphosphorylated ribosomal protein S6 (rpS6) was reduced over six-fold in PRE animals (p<0.05) and total rpS6 protein levels were unchanged between PRE and sedentary animals (p>0.05). We conclude that moderate intensity PRE is sufficient to induce muscle hypertrophy in adolescent animals while the signaling mechanisms associated with muscle hypertrophy may differ between growing adolescents and adults. PMID:22614147

Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

PubMed Central

Kasselman, Lora J.; Veves, Aristidis; Gibbons, Christopher H.; Rutkove, Seward B.

2009-01-01

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23°C) or cold environment (10°C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P = .03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P = .047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted. PMID:20130819

Protection by an oral disubstituted hydroxylamine derivative against loss of retinal ganglion cell differentiation following optic nerve crush.

PubMed

Lindsey, James D; Duong-Polk, Karen X; Dai, Yi; Nguyen, Duy H; Leung, Christopher K; Weinreb, Robert N

2013-01-01

Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

Cardiovascular effects in rats following exposure to a high-boiling coal liquid.

PubMed

Zangar, R C; Sasser, L B; Mahlum, D D; Abhold, R H; Springer, D L

1987-11-01

In previous work, increased blood pressure was observed in anesthetized rats following a subchronic aerosol exposure to solvent-refined coal heavy distillate (HD). To determine if this increase is a permanent, dose-related response, 11-week-old male rats were exposed by inhalation to 0, 0.24, or 0.70 mg/liter (control, low-exposure, and high-exposure groups, respectively) of HD for 6 hr/day, 5 days/week, for 6 weeks. In addition to blood pressure, select cardiovascular parameters were measured to obtain information on other possible toxic effects of the HD and also to gain some insight into potentially altered regulatory mechanisms that could be affecting the blood pressure. The angiotensin-aldosterone hormonal system, body fluid regulation, cardiac function and regulation, and pulmonary gas-exchange capabilities were examined. Two weeks after the end of exposure, mean blood pressures and heart rates of anesthetized animals in the low-and high-exposure groups were elevated relative to the controls. Plasma angiotensin concentrations decreased with increasing dose, whereas aldosterone concentrations were unaffected. In the high-dose group, blood and plasma volumes were 20 and 28%, respectively, higher than those of controls. Seven weeks after exposure, all measured cardiovascular parameters were similar to control values. Results from this study show that a 6-week exposure to HD resulted in dose-dependent, transient changes in a variety of physiological factors considered important in cardiovascular function.

Eight Weeks of Cosmos caudatus (Ulam Raja) Supplementation Improves Glycemic Status in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

PubMed

Cheng, Shi-Hui; Ismail, Amin; Anthony, Joseph; Ng, Ooi Chuan; Hamid, Azizah Abdul; Barakatun-Nisak, Mohd Yusof

2015-01-01

Objectives. Optimizing glycemic control is crucial to prevent type 2 diabetes related complications. Cosmos caudatus is reported to have promising effect in improving plasma blood glucose in an animal model. However, its impact on human remains ambiguous. This study was carried out to evaluate the effectiveness of C. caudatus on glycemic status in patients with type 2 diabetes. Materials and Methods. In this randomized controlled trial with two-arm parallel-group design, a total of 101 subjects with type 2 diabetes were randomly allocated to diabetic-ulam or diabetic controls for eight weeks. Subjects in diabetic-ulam group consumed 15 g of C. caudatus daily for eight weeks while diabetic controls abstained from taking C. caudatus. Both groups received the standard lifestyle advice. Results. After 8 weeks of supplementation, C. caudatus significantly reduced serum insulin (-1.16 versus +3.91), reduced HOMA-IR (-1.09 versus +1.34), and increased QUICKI (+0.05 versus -0.03) in diabetic-ulam group compared with the diabetic controls. HbA1C level was improved although it is not statistically significant (-0.76% versus -0.37%). C. caudatus was safe to consume. Conclusions. C. caudatus supplementation significantly improves insulin resistance and insulin sensitivity in patients with type 2 diabetes.

Morphogenetic events in the perinodal connective tissue in a metastatic cancer model.

PubMed

Conti, G; Minicozzi, A; Merigo, F; Marzola, P; Osculati, F; Cordiano, C; Sbarbati, A

2013-02-01

The modifications of connective tissue surrounding metastatic lymph nodes in a murine model of rectal cancer are described. Athymic nude mice (n=36) were inoculated with 10×10(5) ht-29 cancer cells into the submucosal layer of the rectum. Control mice (n=5) were treated with a sterile buffer. Tumor and the involved lymph nodes were visualized in vivo by magnetic resonance imaging at 1 to 4 weeks after cell injection. After the sacrifice, the excised samples were processed for histology. After one week from cell injection all treated animals developed rectal cancer. Since the first week, neoplastic cells were visible in the nodes. In the surrounding connective tissue, the diameter of the adipocytes was reduced and a mesenchymal-like pattern with stellate cells embedded in an oedematous environment was visible. Since the second week, in the perinodal connective an enlargement of the stroma was present. The tissue was organized in cords and areas with extracellular accumulation of lipids were found. At the fourth week, we observed an enlargement of multilocular areas and lobules of elongated elements almost devoid of lipid droplets. In control animals, in absence of neoplastic masses, pelvic nodes were surrounded by a typical connective tissue characterized by unilocular adipocytes with groups of multilocular adipocytes. We have developed a model of rectal cancer with nodal metastases. Using this model, the work demonstrates that around secondary lesions, the morphogenetic events follow a standard evolution characterized by an early phase with lipolysis and mesenchymalization and later phases with a brown-like phenotype acquisition. Copyright © 2012. Published by Elsevier SAS.

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

Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons.

PubMed

Kaneko, Takao; Tahara, Shoichi; Takabayashi, Fumiyo

2007-11-01

The effects of esculetin (6,7-dihydroxycoumarin) and its 6-glycoside, esculin, on 8-oxo-2'-deoxyguanosine (8-oxodG) formation and carcinogenesis induced by a chemical carcinogen, 1,2-dimethylhydrazine (DMH), were examined in the colons of male Fischer 344 rats. Animals were given water containing esculetin or esculin for 7 d before subcutaneous injection of DMH (20 mg/kg body wt), killed 24 h after DMH treatment, and the levels of thiobarbituric acid reactive substances (TBARS) and 8-oxodG in the colons were determined. Both esculetin and esculin suppressed significantly the DMH-induced increases in 8-oxodG and TBARS in rat colon mucosa. We further investigated the modifying effect of esculin intake on the development of DMH-induced colonic aberrant crypt foci (ACF). Animals were given DMH once a week for 4 weeks to induce ACF. They then received water containing esculin ad libitum for 5 weeks (initiation phase) or 11 weeks after DMH treatment (post-initiation phase). Animals in the positive control group received tap water throughout the experiment. At the end of the experiment (16 weeks), the ingestion of esculin during the initiation phase significantly reduced the incidence of gross tumors, the number of ACF per rat and the mean number of AC per focus, while the esculin treatment during the post-initiation phase significantly decreased only the number of ACF per rat. These results suggest that esculin intake has an inhibitory effect on DMH-induced oxidative DNA damage and carcinogenesis in rat colons.

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.

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)

Health and behavior problems in dogs and cats one week and one month after adoption from animal shelters.

PubMed

Lord, Linda K; Reider, Linda; Herron, Meghan E; Graszak, Kristy

2008-12-01

To characterize health and behavior problems in dogs and cats 1 week and 1 month after adoption from animal shelters and identify factors associated with the likelihood that owners of adopted animals would visit a veterinarian. Cross-sectional study. Sample Population-2,766 (1 week) and 2,545 (1 month) individuals who had adopted an animal from a shelter. Internet and telephone survey responses were collected 1 week and 1 month after animal adoption. Overall, 1,361 of 2,624 (51.9%) dogs and cats had health problems 1 week after adoption, and 239 of 2,312 (10.3%) had a health problem 1 month after adoption. The most common health problem for dogs and cats was respiratory tract disease. A total of 1,630 of 2,689 (60.6%) respondents had taken their animal to a veterinarian within the first week after adoption and 1,865 of 2,460 (75.8%) had within the first month after adoption. Respondents were more likely to have visited a veterinarian if they had adopted a dog versus a cat or if the animal was young (< or = 1 year old), had > or = 1 health problem, or had adjusted moderately to extremely well to its new home within the first month after adoption. Cats had fewer behavior problems than dogs. One week after adoption, the most commonly reported behavior problem was house training for dogs and chewing, digging, or scratching at objects for cats. Results suggested that improvements can be made in the percentage of new owners who visit a veterinarian after adopting an animal from a shelter.

Time course of disassociation of bone formation signals with bone mass and bone strength in sclerostin antibody treated ovariectomized rats.

PubMed

Ma, Yanfei L; Hamang, Matthew; Lucchesi, Jonathan; Bivi, Nicoletta; Zeng, Qianqiang; Adrian, Mary D; Raines, Sarah E; Li, Jiliang; Kuhstoss, Stuart A; Obungu, Victor; Bryant, Henry U; Krishnan, Venkatesh

2017-04-01

Sclerostin antibodies increase bone mass by stimulating bone formation. However, human and animal studies show that bone formation increases transiently and returns to pre-treatment level despite ongoing antibody treatment. To understand its mechanism of action, we studied the time course of bone formation, correlating the rate and extent of accrual of bone mass and strength after sclerostin antibody treatment. Ovariectomized (OVX) rats were treated with a sclerostin-antibody (Scle-ab) at 20mg/kg sc once weekly and sacrificed at baseline and 2, 3, 4, 6, and 8weeks post-treatment. In Scle-ab treated rats, serum PINP and OCN rapidly increased at week 1, peaked around week 3, and returned to OVX control levels by week 6. Transcript analyses from the distal femur revealed an early increase in bone formation followed by a sustained decrease in bone resorption genes. Lumbar vertebral (LV) osteoblast surface increased 88% by week 2, and bone formation rate (BFR/BS) increased 138% by week 4. Both parameters were below OVX control by week 8. Bone formation was primarily a result of modeling based formation. Endocortical and periosteal BFR/BS peaked around week 4 at 313% and 585% of OVX control, respectively. BFR/BS then declined but remained higher than OVX control on both surfaces through week 8. Histomorphometric analyses showed LV-BV/TV did not further increase after week 4, while BMD continued to increase at LV, mid femur (MF), and femoral neck (FN) through week 8. Biomechanical tests showed a similar improvement in bone strength through 8weeks in MF and FN, but bone strength plateaued between weeks 6 and 8 for LV. Our data suggest that bone formation with Scle-ab treatment is rapid and modeling formation dominated in OVX rats. Although transient, the bone formation response persists longer in cortical than trabecular bone. Copyright © 2016 Elsevier Inc. All rights reserved.

Laser myocardial revascularization modulates expression of angiogenic, neuronal, and inflammatory cytokines in a porcine model of chronic myocardial ischemia.

PubMed

Fuchs, Shmuel; Baffour, Richard; Vodovotz, Yoram; Shou, Matie; Stabile, Eugenio; Tio, Fermin O; Leon, Martin B; Kornowski, Ran

2002-01-01

Controversy exists whether transmyocardial laser revascularization (TMR) is associated with angiogenesis or neuromodulation and whether these are time-dependent phenomena. Accordingly, we performed a time-course analysis of the expression of angiogenic and neuronal factors following experimental percutaneous TMR. Five weeks after placing ameroid constrictors on the circumflex coronary artery, 16 pigs underwent left ventricular mapping guided TMR using Ho:YAG laser (2 J x 1 pulse) at 30 sites directed at the ischemic zones and 11 animals were ischemic controls. Histology and immunostaining were obtained at 1 and 2 weeks (4 TMR and 3 controls at each time point) and at 4 weeks (8 TMR and 5 controls) for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), nerve growth factor (betaNGF), substance P (SP), and monocyte chemoattractant protein-1 (MCP-1). Immunoreactivity was scored using a digital image analysis system. Factor VIII staining was used for blood vessel counting. Enhanced regional expression of VEGF, bFGF and MCP-1 in the TMR group was noted at 1 and 2 weeks with a threefold increase at 4 weeks following TMR compared to controls. BetaNGF expression in the TMR group was enhanced at 1 and 2 weeks with subsequent decline at 4 weeks to the controls level. SP expression was not significantly different between groups at all time points. There was a twofold increase in the number of blood vessels in the TMR group at 4 weeks, which was not apparent earlier. These immunohistological findings suggest that cytokines expression compatible with angiogenesis and neuromodulation occurs early after TMR. Up-regulation of angiogenic and inflammatory cytokines may be more sustained than neuromodulation.

Influence of a collagen membrane positioned subjacent the sinus mucosa following the elevation of the maxillary sinus. A histomorphometric study in rabbits.

PubMed

Iida, Takahisa; Carneiro Martins Neto, Evandro; Botticelli, Daniele; Apaza Alccayhuaman, Karol Alí; Lang, Niklaus P; Xavier, Samuel P

2017-12-01

To evaluate the healing after elevation of the sinus mucosa when a collagen membrane was placed between the sinus mucosa and a xenograft used as filler. Eighteen rabbits were used. Sinus mucosa elevation was performed bilaterally, and a collagen membrane was applied subjacent to the sinus mucosa only at a randomly selected test site. At both sites, a collagenated corticocancellous porcine bone was placed within the elevated space and the access window was covered with a collagen membrane. The animals were sacrificed after 2, 4, and 8 weeks of healing, six animals for group. Ground sections were prepared. At the histomorphometric evaluation, the elevated area after 2 and 8 weeks was 11.8 and 8.8 mm 2 at the test, and 10.0 and 5.3 mm 2 at the control sites, respectively. The available area was obtained subtracting the remaining area occupied by the membrane from the elevated area and, after 8 weeks, was 6.7 ± 0.9 mm 2 . After 8 weeks of healing, the mineralized new bone within the elevated space was 18.2 ± 5.5% at the test and 26.7 ± 7.7% at the control sites. Within the available space at the test site, the percentage was 27.3 ± 7.0% after 8 weeks of healing. At 2 and 8 weeks of healing, within the elevated space, the xenograft proportion was 30.9 ± 4.4% and 6.9 ± 2.8% at the test, and 35.2 ± 7.3% and 9.6 ± 4.9% at the control sites, respectively. The placement of a collagen membrane subjacent the sinus mucosa did not reveal any major morphometric difference. The collagen membrane was not completely resorbed after 8 weeks. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experimental evidence supports the abscess theory of development of radicular cysts.

PubMed

Nair, P N R; Sundqvist, Göran; Sjögren, Ulf

2008-08-01

The objective of this study was to experimentally induce inflammatory cysts in an animal model so as to test the hypothesis that radicular cysts develop via the "abscess pathway." Twenty-eight perforated custom-made Teflon cages were surgically implanted into defined locations in the back of 7 Sprague Dawley rats. A week after the implantation of the cages, a known quantity of freshly grown, close allogeneic oral keratinocytes in phosphate buffer solution (PBS) was injected into each cage. One cage per animal was treated as the control that received only epithelial cells. The remaining 3 cages of each animal were trials. Seven days post epithelial cell inoculation; a suspension of 0.2 mL of Fusobacterium nucleatum (10(8) bacteria per mL) was injected into each of the 3 trial cages. Two, 12, and 24 weeks after the inoculation of the bacteria, the cages were taken out, and the tissue contents were fixed and processed by correlative light and transmission electron microscopy. Sixteen of the 21 trial cages could be processed and yielded results. Inoculations of epithelial cells followed 1 week later by F. nucleatum into tissue cages resulted in the development inflammatory cysts in 2 of the 16 cages. The 2 cages contained a total of 4 cystic sites. None of the control cages showed the presence of any cyst-like pathology. Inflammatory cysts were induced by initiating acute inflammatory foci (abscess/necrotic area) by bacterial injection that got enclosed by a proliferating epithelium. This finding provides strong experimental evidence in support of the "abscess theory" of development of radicular cysts.

Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.

PubMed

Serafín, Anna; Molín, Jessica; Márquez, Merce; Blasco, Ester; Vidal, Enric; Foradada, Laia; Añor, Sonia; Rabanal, Rosa M; Fondevila, Dolors; Bosch, Fàtima; Pumarola, Martí

2010-05-01

Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.

Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat model.

PubMed

Angeline, Michael E; Ma, Richard; Pascual-Garrido, Cecilia; Voigt, Clifford; Deng, Xiang Hua; Warren, Russell F; Rodeo, Scott A

2014-01-01

Few studies have considered hormonal influences, particularly vitamin D, on healing. Vitamin D deficiency would have a negative effect on the structure of the healing tendon-bone interface in a rat model and would result in decreased tendon attachment strength. Controlled laboratory study. Vitamin D deficiency was induced in 28 male Sprague-Dawley rats using a specialized vitamin D-deficient diet and ultraviolet light restriction. Serum levels of vitamin D were measured after 6 weeks. These vitamin D-deficient animals (experimental group) plus 32 rats with normal vitamin D levels (controls) underwent unilateral detachment of the right supraspinatus tendon from the greater tuberosity of the humerus, followed by immediate repair using bone tunnel suture fixation. The animals were sacrificed at 2- and 4-week intervals after surgery for biomechanical analysis. A paired t test was used to compare serum vitamin D levels at day 0 and at 6 weeks. A nonparametric Mann-Whitney U test was used to compare load-to-failure and stiffness values between the experimental group and controls. Bone density and new bone formation at the tendon insertion site on the greater tuberosity were assessed with micro-computed tomography (CT). The organization of collagen tissue, new bone formation, vascularity at the tendon-bone interface, fibrocartilage at the tendon-bone interface, and collagen fiber continuity between the tendon and bone tissue were evaluated with safranin O and picrosirius red staining. Blood draws confirmed vitamin D deficiency at 6 weeks compared with time zero/baseline for rats in the experimental group (10.9 ng/mL vs 6.5 ng/mL, respectively; P < .001). Biomechanical testing demonstrated a significant decrease in load to failure in the experimental group compared with controls at 2 weeks (5.8 ± 2.0 N vs 10.5 ± 4.4 N, respectively; P < .006). There was no difference in stiffness at 2 weeks between the control and experimental groups. At 4 weeks, there was no significant difference in load to failure or stiffness between the control and experimental groups. Histological analysis showed less bone formation and less collagen fiber organization in the vitamin D-deficient specimens at 4 weeks as compared with controls. Micro-CT analysis showed no significant difference between groups for total mineral density and bone volume fraction of cortical, whole, or trabecular bone at 4 weeks. The biomechanical and histological data from this study suggest that low vitamin D levels may negatively affect early healing at the rotator cuff repair site. It is estimated that 1 billion people worldwide are vitamin D deficient. In the deficient state, acutely injured rotator cuffs may have a reduced ability for tendon healing. Further studies are needed to determine the exact mechanism by which vitamin D affects tendon healing and whether vitamin D supplementation can improve rotator cuff tendon healing and reduce the incidence of retears.

Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

PubMed

O'Connor, Gregory; Jeffrey, Elisabeth; Madorma, Derik; Marcillo, Alexander; Abreu, Maria T; Deo, Sapna K; Dietrich, W Dalton; Daunert, Sylvia

2018-06-07

Although there has been a significant amount of research focused on the pathophysiology of spinal cord injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals because of the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we used a thoracic SCI rat model and investigated changes to the microbiota, proinflammatory cytokine levels, and bacterial communication molecule levels post-injury and gentamicin treatment for 7 days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 operational taxonomic units were enriched in the SCI animal group and three were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Proinflammatory cytokines interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha were found to be significantly elevated in intestinal tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

Experimental Model of Tuberculosis in the Domestic Goat after Endobronchial Infection with Mycobacterium caprae ▿

PubMed Central

Pérez de Val, Bernat; López-Soria, Sergio; Nofrarías, Miquel; Martín, Maite; Vordermeier, H. Martin; Villarreal-Ramos, Bernardo; Romera, Nadine; Escobar, Manel; Solanes, David; Cardona, Pere-Joan; Domingo, Mariano

2011-01-01

Caprine tuberculosis (TB) has increased in recent years, highlighting the need to address the problem the infection poses in goats. Moreover, goats may represent a cheaper alternative for testing of prototype vaccines in large ruminants and humans. With this aim, a Mycobacterium caprae infection model has been developed in goats. Eleven 6-month-old goats were infected by the endobronchial route with 1.5 × 103 CFU, and two other goats were kept as noninfected controls. The animals were monitored for clinical and immunological parameters throughout the experiment. After 14 weeks, the goats were euthanized, and detailed postmortem analysis of lung lesions was performed by multidetector computed tomography (MDCT) and direct observation. The respiratory lymph nodes were also evaluated and cultured for bacteriological analysis. All infected animals were positive in a single intradermal comparative cervical tuberculin (SICCT) test at 12 weeks postinfection (p.i.). Gamma interferon (IFN-γ) antigen-specific responses were detected from 4 weeks p.i. until the end of the experiment. The humoral response to MPB83 was especially strong at 14 weeks p.i. (13 days after SICCT boost). All infected animals presented severe TB lesions in the lungs and associated lymph nodes. M. caprae was recovered from pulmonary lymph nodes in all inoculated goats. MDCT allowed a precise quantitative measure of TB lesions. Lesions in goats induced by M. caprae appeared to be more severe than those induced in cattle by M. bovis over a similar period of time. The present work proposes a reliable new experimental animal model for a better understanding of caprine tuberculosis and future development of vaccine trials in this and other species. PMID:21880849

Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques.

PubMed

Marcario, Joanne K; Pendyala, Gurudutt; Riazi, Mariam; Fleming, Kandace; Marquis, Janet; Callen, Shannon; Lisco, Steven J; Fowler, Stephen C; Cheney, Paul D; Buch, Shilpa J

2016-06-01

The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results is that behavioral decline occurred with high CSF viral loads but not necessarily with high plasma viral loads. Compared to saline controls, all treated animals showed significant decreases in performance on all three behavioral tasks during the morphine-only dependency period. During the post infection period, only the morphine plus SIV group showed a significant further decline and this only occurred for the MS task. Taken together, these data demonstrate a clear effect of morphine to produce behavioral deficits and also suggest that morphine can act synergistically with SIV/HIV to exacerbate behavioral deficits.

Effects of morphine on behavioral task performance in SIV-infected Rhesus macaques

PubMed Central

Marcario, Joanne K; Pendyala, Gurudutt; Riazi, Mariam; Fleming, Kandace; Marquis, Janet; Callen, Shannon; Lisco, Steven J; Fowler, Stephen C.; Cheney, Paul D; Buch, Shilpa J

2016-01-01

The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results is that behavioral decline occurred with high CSF viral loads but not necessarily with high plasma viral loads. Compared to saline controls, all treated animals showed significant decreases in performance on all three behavioral tasks during the morphine-only dependency period. During the post infection period, only the morphine plus SIV group showed a significant further decline and this only occurred for the MS task. Taken together, these data demonstrate a clear effect of morphine to produce behavioral deficits and also suggest that morphine can act synergistically with SIV/HIV to exacerbate behavioral deficits. PMID:27039332

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kawata, Daisuke; Wu, Zetang

2017-09-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

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.

Evaluation of the phosphodiesterase 3 inhibitor ORG 9935 as a contraceptive in female macaques: initial trials.

PubMed

Jensen, Jeffrey T; Stouffer, Richard L; Stanley, Jessica E; Zelinski, Mary B

2010-02-01

The study was conducted to determine whether a phosphodiesterase (PDE) 3 inhibitor has potential as a novel contraceptive in primates. Regularly cycling adult female cynomolgus macaques of proven fertility (n=16) were treated for 7 months with placebo (controls) or the PDE3 inhibitor ORG 9935 as a daily food treat (150 mg/kg) or as a weekly depot injection (150 mg/kg, sc). After 1 month, a male of proven fertility was introduced into each group. Females underwent weekly monitoring of progesterone (P) and ultrasound evaluation for pregnancy if P remained elevated (1.0 ng/mL) >3 weeks. ORG 9935 values were evaluated using high-performance liquid chromatography. Overall, the pregnancy rate in ORG 9935-treated monkeys (4/8, 50%) did not differ from controls (7/8, 88%; p=.5). However, no animal became pregnant in a cycle when the serum level of ORG 9935 exceeded 300 nmol/L. Moreover, two treated monkeys who mated throughout the treatment phase and did not conceive became pregnant within four cycles after stopping ORG 9935. The other two animals were discontinued prematurely from the protocol. These results demonstrate that ORG 9935 may prevent pregnancy in primates at serum concentrations above 300 nmol/L and that the effect is reversible.

Metabolic alkalosis during immobilization in monkeys (M. nemestrina)

NASA Technical Reports Server (NTRS)

Young, D. R.; Yeh, I.; Swenson, R. S.

1983-01-01

The systemic and renal acid-base response of monkeys during ten weeks of immobilization was studied. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

Postangioplasty Restenosis Followed with Magnetic Resonance Imaging in an Atherosclerotic Rabbit Model

PubMed Central

Hänni, Mari; Leppänen, Olli; Smedby, Örjan

2012-01-01

Rationale and Objectives. Testing a quantitative, noninvasive method to assess postangioplasty vessel wall changes in an animal model. Material and Methods. Six New Zealand white rabbits were subjected to atherosclerotic injury, including cholesterol-enriched diet, deendothelialization, and percutaneous transluminal angioplasty (PTA) in the distal part of abdominal aorta (four weeks after deendothelialization). The animals were examined with a 1.5T MRI scanner at three times as follows: baseline (six weeks after diet start and two days after PTA) and four weeks and 10 weeks after-PTA. Inflow angiosequence (M2DI) and proton-density-weighted sequence (PDW) were performed to examine the aorta with axial slices. To identify the inner and outer vessel wall boundaries, a dynamic contour algorithm (Gradient Vector Flow Snakes) was applied to the images, followed by calculation of the vessel wall dimensions. The results were compared with histopathological analysis. Results. The wall thickness in the lesion was significantly higher than in the control region at 4 and 10 weeks, reflecting induction of experimentally created after-angioplasty lesion. At baseline, no significant difference between the two regions was present. Conclusions. It is possible to follow the development of vessel wall changes after-PTA with MRI in this rabbit model. PMID:23316216

Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

NASA Astrophysics Data System (ADS)

Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

1989-06-01

Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

Effect of experimental glaucoma on the non-image forming visual system.

PubMed

de Zavalía, Nuria; Plano, Santiago A; Fernandez, Diego C; Lanzani, María Florencia; Salido, Ezequiel; Belforte, Nicolás; Sarmiento, María I Keller; Golombek, Diego A; Rosenstein, Ruth E

2011-06-01

Glaucoma is a leading cause of blindness worldwide, characterized by retinal ganglion cell degeneration and damage to the optic nerve. We investigated the non-image forming visual system in an experimental model of glaucoma in rats induced by weekly injections of chondroitin sulphate (CS) in the eye anterior chamber. Animals were unilaterally or bilaterally injected with CS or vehicle for 6 or 10 weeks. In the retinas from eyes injected with CS, a similar decrease in melanopsin and Thy-1 levels was observed. CS injections induced a similar decrease in the number of melanopsin-containing cells and superior collicular retinal ganglion cells. Experimental glaucoma induced a significant decrease in the afferent pupil light reflex. White light significantly decreased nocturnal pineal melatonin content in control and glaucomatous animals, whereas blue light decreased this parameter in vehicle- but not in CS-injected animals. A significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was observed in glaucomatous animals. General rhythmicity and gross entrainment appear to be conserved, but glaucomatous animals exhibited a delayed phase angle with respect to lights off and a significant increase in the percentage of diurnal activity. These results indicate the glaucoma induced significant alterations in the non-image forming visual system. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease.

PubMed

Kirsch, Richard; Sijtsema, Helene P; Tlali, Mpho; Marais, Adrian D; Hall, Pauline de la M

2006-12-01

This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD). Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and DL-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated. Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P < 0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P < 0.02) and decreased hepatic steatosis (P < 0.01), hepatic triglyceride levels (P < 0.01), hepatic-conjugated dienes (CD; P < 0.02) and serum ALT levels (P < 0.002) at 12 weeks. Reduced hepatic steatosis (P < 0.005) and CD (P < 0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content. Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.

Concentration of ofloxacin in canine prostate tissue and prostate fluid after intraprostatic injection of biodegradable sustained-releasing microspheres containing ofloxacin.

PubMed

Bahk, J Y; Hyun, J S; Lee, J Y; Kim, J; Cho, Y H; Lee, J H; Park, J S; Kim, M O

2000-05-01

Excellent treatment results in chronic prostatitis by direct intra-prostatic injection of antibiotic were reported several decades ago with only minimal scientific background. We examined the distribution, in prostatic tissue and fluid, of the antibiotic in canines after intra-prostatic injection of biodegradable sustained-releasing microspheres containing 12 mg. of ofloxacin. A total of 36 male dogs, 12 controls and 24 experimental, older than 2 years, were used. Experimental dogs were given biodegradable sustained releasing microspheres containing ofloxacin 12 mg. and poly(D,L-lactic) acid 28 mg., designed to release over more than a 4 week period. The 12 control animals were divided into 2 groups, and oral ofloxacin 100 mg. was given twice a day for 2 and 4 weeks. The 24 experimental animals were divided into 4 subgroups of 6 dogs each, 4 for prostatic tissue and 2 for prostatic fluid level of ofloxacin determination. Anesthesia was initiated with ketamine HCl and xylazine, and maintained with intermittent ketamine HCl. In the experimental groups, 1 ml. of resolved formula was injected into one lobe of surgically exposed prostates. The concentration of ofloxacin was measured by high performance liquid chromatography (HPLC) of blood, prostatic tissue and prostatic fluid. Pilocarpine 0.5 mg./kg. was used for the collection of the prostatic fluid. The total ofloxacin of controls were 2,800 (2 weeks) and 5,600 (4 weeks) mg. In control groups, tissue concentrations of ofloxacin were relatively even at all segments of prostate, 7.4 +/- 0.8 (2 weeks) and 9.2 +/- 1.1 microg./ml. (4 weeks). The blood level ranged between 3.6 to 5.1 microg./ml. The prostatic fluid level ranged from 3.1 to 5.7 microg. /ml. In the experimental groups, the tissue levels of ofloxacin were 10.5 +/- 3.0 (1 week), 13.8 +/- 4.5 (2 weeks), 7.1 +/- 0.9 (3 weeks) and 7.7 +/- 3.0 microg./ml. (4 weeks) in the injected lobe. The opposite lobes were 8.0 +/- 1.1 (1 week), 10.2 +/- 4.2 (2 weeks), 5. 1 +/- 1.4 (3 weeks) and 7.6 +/- 0.8 (4 weeks) microg./ml. The blood level in the experimental groups ranged between 0.16 to 0.59 microg./ml. The prostate fluid level ranged from 2.9 to 6.1 microg./ml. in 8 dogs. Upon pathologic examination, the microspheres were interposed between prostate stroma and their size was reduced over time. Our study indicates that there is communication between the right and left prostate lobes. Direct injection of biodegradable sustained releasing ofloxacin formula into the prostate may be a substitute for long term antibiotic medication in humans for chronic prostatitis in the future without hurting the minimal inhibitory concentration(MIC)90.

Evaluation of Polyurethane Nasolacrimal Duct Stents: In Vivo Studies in New Zealand Rabbits

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

Wilhelm, K.E., E-mail: wilhelm@uni-bonn.de; Grabolle, B.; Urbach, H.

2006-10-15

The purpose of this study was to evaluate the radiographic and biological effects of different polyurethane nasolacrimal duct stents in an animal model. Fifteen polyurethane nasolacrimal duct stents (n = 5 mushroom-type stents, n = 5 newly designed S-shaped TearLeader stents without hydrophilic coating, and n = 5 S-shaped TearLeader stents with hydrophilic coating) were implanted in the nasolacrimal ducts of eight unaffected New Zealand rabbits. One nasolacrimal system served as control. Clinical and radiographic follow-up was performed at 1-, 2-, and 4-week intervals, then after a 3-month interval, after which the animals were euthanized. All stents were implanted withoutmore » major periprocedural complications. The stents proved to be patent by the end of the procedure. During follow-up, all mushroom-type stents were occluded at 4 weeks. None of these stents opened to forced irrigation. Clinically, all rabbits demonstrated severe dacryocystitis. Three out of five TearLeader stents without hydrophilic coating were blocked at 4 weeks; one out of five was open to irrigation. Best results were observed in the stent group with hydrophilic coating. Follow-up dacryocystography demonstrated patent stents in nasolacrimal ducts of all animals after 4 weeks. In only one of five cases, the coated stent became partially occluded after 2 months. These animals were free of clinical symptoms. After 3 months, at least three out of five stents still opened to forced irrigation and only one stent was completely blocked. Dislocation of the stents was not observed. Refinement of the stent surface and stent design improves the results of nasolacrimal duct stenting in this animal model. Implantation of hydrophilic-coated S-shaped stents is highly superior to conventional mushroom-type stents and noncoated stent types. Hydrophilic coating seems to prevent foreign-body reactions, resulting in maximized stent patency.« less

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Moderate intensity physical activity prevents increased blood glucose concentrations, fat pad deposition and cardiac action potential prolongation following diet-induced obesity in a juvenile-adolescent rat model.

PubMed

van Waveren, Alannah; Duncan, Mitch J; Coulson, Fiona R; Fenning, Andrew

2014-01-01

Both obesity and a lack of physical activity have been associated with an elevated risk of cardiovascular disease (CVD). The incidence of obesity is increasing, especially in juvenile-adolescents. While there is limited research examining the chronic effects of obesity in adolescent humans and animal models of this condition, little is also known concerning how moderate physical activity might prevent or attenuate secondary cardiovascular complications induced by obesity during adolescence. We investigated the effects of diet-induced obesity (consisting of a high-fat, high-carbohydrate diet (HFHC)) on biometric indices, vascular and airway function, cardiovascular function, systemic oxidative stress and markers of inflammation in a juvenile-adolescent rodent model. Four groups were used: control (CON), physical activity (PA) treated, HFHC and HFHC + PA (n = 16 per group). HFHC feeding started at 4 weeks of age for a period of 12 weeks. Physical activity treatment was initiated (PA and HFHC + PA groups) when the animals were 8 weeks of age, for 8 weeks. Physical activity in juvenile-adolescent healthy rats showed no change in comparison to the CON group in all experimental parameters except for increases in lipid peroxidation, decreases in inflammatory cytokines, improvements in vascular reactivity and decreased atrial responses to positive chronotropic agents. The HFHC animals were mildly hyperglycemic, hypertensive, displayed renal hypertrophy and showed increased retroperitoneal fat pad deposition compared to the CON group. HFHC + PA rats were also hypertensive, however showed improvements in cardiac electrophysiology, body weight, fat pad deposition and inflammatory signaling, in comparison to the HFHC fed rats and CON animals. In conclusion, in a juvenile-adolescent animal model of diet-induced obesity engagement in physical activity is beneficial in reducing the inflammatory effects of obesity.

Effect of cutaneous and digestive colonization in the induction of anti-Candida albicans antibodies: experimental study.

PubMed

Nogueira, J M; Garcia-de-Lomas, J; Buesa, F J; Prat, J; Mir, A; Camarena, J J

1985-10-01

Candida albicans colonization induces antibodies, which must be taken into account in the serological diagnosis of candidiasis. In order to determine the degree of this effect, an experimental study in rabbits free of specific anti-Candida antibodies by cutaneous and digestive inoculation has been carried out. The evolution of humoral response was studied over 8 weeks by indirect immunofluorescence (IIF), direct agglutination (DA), counterimmunoelectrophoresis (CIE) and double diffusion (DD). The cutaneous colonization detectable by culture was maintained until the second week in 70% of the animals and the presence of antibodies detectable by IIF and DA was observed after the 2nd week. The highest antibody titre by IFF and DA was 1/64, and was reached in the 5th week, with a tendency to drop in the following weeks. Precipitins were only detected by CIE in 15% of the animals in the 7th week. Elimination of yeast in stools continued only in 20% of the animals in the 2nd week of the experiment. Antibodies were detected by IIF and DA after the 2nd week, with the highest titres detectable by IFF in the 5th week. Precipitant antibodies detectable by CIE appeared in 15% of the animals in the 8th week.

Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists.

PubMed

Mills, P K; Annegers, J F; Phillips, R L

1988-03-01

Seventh-day Adventist women experience lower mortality rates from breast cancer than other white females in the United States. To evaluate the role of diet in relation to breast cancer within this unique population (more than one-half of all Adventist women are lacto-ovo-vegetarians), a nested case-control study was conducted including 142 cases of fatal breast cancer and 852 matched controls among California Seventh-day Adventist women in 1960-1980. No significant relations between the consumption of animal products (meat, milk, cheese, and eggs) and breast cancer were evident. Odds ratios of 1.00, 1.22, and 1.03 were observed for meat consumption categories of none or occasional, 1-3 days/week, and 4+ days/week, respectively. However, among those women who experienced a relatively early age at natural menopause (less than or equal to 48 years), a suggestive though nonsignificant, positive association between meat consumption and risk was noted. These relations remained unchanged after simultaneously controlling for the effects of other covariates (menstrual characteristics and obesity) via conditional logistic regression analysis. Risk was not related to age at first exposure to the vegetarian lifestyle nor to duration of exposure to the vegetarian lifestyle.

Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress.

PubMed

Strekalova, Tatyana; Gorenkova, Natalia; Schunk, Edward; Dolgov, Oleg; Bartsch, Dusan

2006-05-01

A stress-induced decrease in sucrose preference in rodents is regarded as an analog of anhedonia, a key symptom of depression. We investigated the effects of citalopram, administrated via drinking water (15 mg/kg/day), in a mouse model of stress-induced anhedonia. In this model, chronic stress induces anhedonia in a subset of C57BL/6N mice, while the remaining animals do not show a hedonic deficit or other depressive-like behaviors, although they are exposed to the same stressors as the anhedonic mice. Pre-stress and post-stress treatment with citalopram counteracted the development and maintenance of anhedonia and rescued normal floating in the forced swim test, demonstrating an antidepressant-like action. During the post-stress treatment, citalopram selectively increased sucrose preference and intake on the fourth week of treatment in anhedonic mice without affecting non-anhedonic animals. Citalopram also decreased elevated water consumption in the anhedonic group. Citalopram, administered 1 week before and during a 4-week stress procedure, decreased the percentage of anhedonic mice and reduced the increase of water intake in stressed mice. This study suggests that our chronic stress paradigm can serve as a model of anhedonia, in which antidepressant treatment is selectively effective in animals with a hedonic deficit.

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

PubMed

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

2015-07-16

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

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure

NASA Technical Reports Server (NTRS)

Ding, B.; Price, R. L.; Goldsmith, E. C.; Borg, T. K.; Yan, X.; Douglas, P. S.; Weinberg, E. O.; Bartunek, J.; Thielen, T.; Didenko, V. V.;

Moderate Aerobic Training Improves Cardiorespiratory Parameters in Elastase-Induced Emphysema

PubMed Central

Henriques, Isabela; Lopes-Pacheco, Miquéias; Padilha, Gisele A.; Marques, Patrícia S.; Magalhães, Raquel F.; Antunes, Mariana A.; Morales, Marcelo M.; Rocha, Nazareth N.; Silva, Pedro L.; Xisto, Débora G.; Rocco, Patricia R. M.

2016-01-01

Aim: We investigated the therapeutic effects of aerobic training on lung mechanics, inflammation, morphometry and biological markers associated with inflammation, and endothelial cell damage, as well as cardiac function in a model of elastase-induced emphysema. Methods: Eighty-four BALB/c mice were randomly allocated to receive saline (control, C) or 0.1 IU porcine pancreatic elastase (emphysema, ELA) intratracheally once weekly for 4 weeks. After the end of administration period, once cardiorespiratory impairment associated with emphysema was confirmed, each group was further randomized into sedentary (S) and trained (T) subgroups. Trained mice ran on a motorized treadmill, at moderate intensity, 30 min/day, 3 times/week for 4 weeks. Results: Four weeks after the first instillation, ELA animals, compared to C, showed: (1) reduced static lung elastance (Est,L) and levels of vascular endothelial growth factor (VEGF) in lung tissue, (2) increased elastic and collagen fiber content, dynamic elastance (E, in vitro), alveolar hyperinflation, and levels of interleukin-1β and tumor necrosis factor (TNF)-α, and (3) increased right ventricular diastolic area (RVA). Four weeks after aerobic training, ELA-T group, compared to ELA-S, was associated with reduced lung hyperinflation, elastic and collagen fiber content, TNF-α levels, and RVA, as well as increased Est,L, E, and levels of VEGF. Conclusion: Four weeks of regular and moderate intensity aerobic training modulated lung inflammation and remodeling, thus improving pulmonary function, and reduced RVA and pulmonary arterial hypertension in this animal model of elastase-induced emphysema. PMID:27536247

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.

Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning.

PubMed

Cardoso, Armando; Marrana, Francisco; Andrade, José P

2016-09-01

It is widely known that caloric restriction (CR) has benefits on several organic systems, including the central nervous system. However, the majority of the CR studies was performed in adult animals and the information about the consequences on young populations is limited. In this study, we analyzed the effects of young-onset CR, started at 4weeks of age, in the number of neuropeptide Y (NPY)-containing neurons and in neurogenesis of the hippocampal formation, using doublecortin (DCX) and Ki67 as markers. Knowing that CR treatment could interfere with exploratory activity, anxiety, learning and memory we have analyzed the performance of the rats in the open-field, elevated plus-maze and Morris water maze tests. Animals aged 4weeks were randomly assigned to control or CR groups. Controls were maintained in the ad libitum regimen during 2months. The adolescent CR rats were fed, during 2months, with 60% of the amount of food consumed by controls. We have found that young-onset CR treatment did not affect the total number of NPY-immunopositive neurons in dentate hilus, CA3 and CA1 hippocampal subfields and did not change the exploratory activity and anxiety levels. Interestingly, we have found that young-onset CR might affect spatial learning process since those animals showed worse performance during the acquisition phase of Morris water maze. Furthermore, young-onset CR induced alterations of neurogenesis in the dentate subgranular layer that seems to underlie the impairment of spatial learning. Our data suggest that adolescent animals are vulnerable to CR treatment and that this diet is not suitable to be applied in this age phase. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of a cold-adapted, intranasal, equine influenza vaccine: challenge trials.

PubMed

Townsend, H G; Penner, S J; Watts, T C; Cook, A; Bogdan, J; Haines, D M; Griffin, S; Chambers, T; Holland, R E; Whitaker-Dowling, P; Youngner, J S; Sebring, R W

2001-11-01

A randomised, controlled, double-blind, influenza virus, aerosol challenge of horses was undertaken to determine the efficacy of a cold-adapted, temperature sensitive, modified-live virus, intranasal, equine influenza vaccine. Ninety 11-month-old influenza-naïve foals were assigned randomly to 3 groups (20 vaccinates and 10 controls per group) and challenged 5 weeks, 6 and 12 months after a single vaccination. Challenges were performed on Day 0 in a plastic-lined chamber. Between Days 1 and 10, animals were examined daily for evidence of clinical signs of influenza. Nasal swabs for virus isolation were obtained on Day 1 and Days 1 to 8 and blood samples for serology were collected on Days 1, 7 and 14. There was no adverse response to vaccination in any animal. Following challenge at 5 weeks and 6 months, vaccinates had significantly lower clinical scores (P = 0.0001 and 0.005, respectively), experienced smaller increases in rectal temperature (P = 0.0008 and 0.0007, respectively) and shed less virus (P<0.0001 and P = 0.03, respectively) over fewer days (P<0.0001 and P = 0.002, respectively) than did the controls. After the 12 month challenge, rectal temperatures (P = 0.006) as well as the duration (P = 0.03) and concentration of virus shed (P = 0.04) were significantly reduced among vaccinated animals. The results of this study showed that 6 months after a single dose of vaccine the duration and severity of clinical signs were markedly reduced amongst vaccinated animals exposed to a severe live-virus challenge. Appropriate use of this vaccine should lead to a marked reduction in the frequency, severity and duration of outbreaks of equine influenza in North America.

Bariatric Embolization: Pilot Study on the Impact of Gastroprotective Agents and Arterial Distribution on Ulceration Risk and Efficacy in a Porcine Model.

PubMed

Paxton, Ben E; Arepally, Aravind; Alley, Christopher L; Kim, Charles Y

2016-12-01

To assess whether the number of fundal arteries embolized and use of gastroprotective agents have an impact on ghrelin suppression and gastric ulceration rates. Twenty-two healthy, growing swine (mean, 38.4 kg; range, 30.3-47.0 kg) were evaluated. Six control swine underwent a sham procedure. Gastric embolization was performed by the infusion of 40-µm microspheres selectively into some or all gastric arteries supplying the gastric fundus. In group 1, 6 swine underwent embolization of all 4 arteries to the gastric fundus. In group 2, 5 swine underwent embolization of 2 gastric fundal arteries. In group 3, 5 swine underwent embolization of 1 gastric fundal artery. Animals in groups 2 and 3 were treated with gastroprotective agents (sucralfate and omeprazole). Weight and fasting plasma ghrelin levels were analyzed at baseline and at week 4. Upon animal euthanasia, gross analysis was performed for identification of ulcers. Only group 1 animals exhibited changes in serum ghrelin levels that rendered them significantly lower than those in control animals (P = .049). Group 3 animals exhibited marked elevations in serum ghrelin levels compared with control animals (P = .001). Gross pathologic evaluation revealed 0 ulcers in the control animals, 3 ulcers (50%) in group 1, 2 ulcers (40%) in group 2, and 2 ulcers (40%) in group 3. Administration of gastroprotective agents and embolization of fewer arteries to the gastric fundus did not prevent gastric ulceration in treated animals. Only animals that underwent embolization of all gastric arteries exhibited significant decreases in serum ghrelin levels. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

A Novel Multi-Phosphonate Surface Treatment of Titanium Dental Implants: A Study in Sheep

PubMed Central

von Salis-Soglio, Marcella; Stübinger, Stefan; Sidler, Michéle; Klein, Karina; Ferguson, Stephen J.; Kämpf, Käthi; Zlinszky, Katalin; Buchini, Sabrina; Curno, Richard; Péchy, Péter; Aronsson, Bjorn-Owe; von Rechenberg, Brigitte

2014-01-01

The aim of the present study was to evaluate a new multi-phosphonate surface treatment (SurfLink®) in an unloaded sheep model. Treated implants were compared to control implants in terms of bone to implant contact (BIC), bone formation, and biomechanical stability. The study used two types of implants (rough or machined surface finish) each with either the multi-phosphonate Wet or Dry treatment or no treatment (control) for a total of six groups. Animals were sacrificed after 2, 8, and 52 weeks. No adverse events were observed at any time point. At two weeks, removal torque showed significantly higher values for the multi-phosphonate treated rough surface (+32% and +29%, Dry and Wet, respectively) compared to rough control. At 52 weeks, a significantly higher removal torque was observed for the multi-phosphonate treated machined surfaces (+37% and 23%, Dry and Wet, respectively). The multi-phosphonate treated groups showed a positive tendency for higher BIC with time and increased new-old bone ratio at eight weeks. SEM images revealed greater amounts of organic materials on the multi-phosphonate treated compared to control implants, with the bone fracture (from the torque test) appearing within the bone rather than at the bone to implant interface as it occurred for control implants. PMID:25215424

Delayed puberty caused by hyperthyroidism in ram lambs is not a result of suppression in body growth.

PubMed

Chandrasekhar, Y; D'Occhio, M J; Setchell, B P

1986-03-01

Over a period of 8 weeks ram lambs (16 weeks old) were made hyperthyroidal (serum thyroxine approximately equal to 150 ng/ml, compared with control approximately equal to 48 ng/ml) by daily subcutaneous injections of thyroxine or maintained at a constant body weight by restriction of the feed intake. Hyperthyroidal and restricted-intake lambs remained at a constant body weight during the period of treatment whilst control rams gained body weight. Testicular growth was normal in restricted-intake lambs but was suppressed in hyperthyroidal animals. Hyperthyroidism, but not feed restriction, was also associated with decrease in LH pulse frequency (1.3 +/- 0.3/12 h compared with controls 4.8 +/- 0.9/12 h. Hyperthyroidal lambs showed normal LH responses to exogenous LHRH. After cessation of treatment testicular growth continued to be suppressed for up to 16 weeks in previously hyperthyroidic rams; thereafter testes began to increase in size but at 30 weeks after treatment were still smaller than those of control rams. It is concluded that elevated thyroxine concentrations directly influence sexual maturation in ram lambs through actions at hypothalamic and/or higher brain centres which control LH secretion. Transient hyperthyroidism during sexual maturation may cause permanent impairment of sexual development.

[Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

PubMed

Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

1997-12-01

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

PubMed

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P < 0.05). Tissue-engineered bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

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 chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

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

Heidor, Renato; Advanced Research Center in Food Science and Nutrition; Furtado, Kelly Silva

2014-04-15

The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MDmore » group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.« less

Gonadal and extra-gonadal sperm reserves and sperm production of pubertal rabbits fed dietary fumonisin B1.

PubMed

Ewuola, E O; Egbunike, G N

2010-06-01

The influence of fumonisin B(1) (a mycotoxin produced by Fusarium verticillioides) on sperm reserves and production of crossbred pubertal rabbits was studied using an experimental model that lasted 28 weeks. Forty-eight male rabbits, 7 weeks old and with average weight of 757.50+/-0.50 g, were allotted to four dietary fumonisin B(1) concentrations of 0.13, 5.0, 7.5 and 10.0 mg kg(-1) constituting diets 1 (control), 2, 3 and 4, respectively. The paired testes weight of rabbits fed diet 3 was significantly (P<0.05) higher than those fed diet 2 and the control. However, the epididymal weight was significantly (P<0.05) lower in rabbits fed the control diet as compared to others on test diets. The gonadal sperm reserves of the animals were significantly (P<0.05) reduced by the toxin with increased concentrations of the toxin in the diets. The sperm reserves per testis and per gram testis were significantly (P<0.05) higher in the control rabbits than those fed diets 3 and 4. The sperm reserves in caput, corpus and caudal epididymis declined significantly with each increase in the fumonisin concentration in the diets. The number of spermatozoa in total caput, corpus and cauda was significantly (P<0.05) higher in rabbits fed the control diet and the least in rabbits fed diet 4 containing 10.0mg fumonisin B(1)/kg. Extra-gonadal sperm reserves significantly decreased (P<0.05) in rabbits fed diets 3 and 4 compared to the control. The daily sperm production of the animals fed diets 2, 3 and 4 declined significantly to 67, 59 and 36% relative to those animals fed the control diet. This study suggests that exposure of breeding male rabbits to diets contaminated with fumonisin B(1) up to 7.5 mg fumonisin B(1)/kg will depress testicular and epididymal sperm reserves and sperm production and potentially impair reproduction in the animals. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Enzymatic recontouring of auricular cartilage in a rabbit model.

PubMed

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

2005-01-01

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

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.

Vasculogenesis and Diabetic Erectile Dysfunction: How Relevant Is Glycemic Control?

PubMed

Castela, Angela; Gomes, Pedro; Silvestre, Ricardo; Guardão, Luísa; Leite, Liliana; Chilro, Rui; Rodrigues, Ilda; Vendeira, Pedro; Virag, Ronald; Costa, Carla

2017-01-01

Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2017-05-15

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

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.

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

PubMed

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

2009-05-06

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

Immunogenicity and protective efficacy of heparan sulphate binding proteins of Entamoeba histolytica in a guinea pig model of intestinal amoebiasis.

PubMed

Kaur, Upninder; Khurana, Sumeeta; Saikia, Uma Nahar; Dubey, M L

2013-11-01

Entamoeba histolytica infection is associated with considerable morbidity and mortality in the form of intestinal and extraintestinal amoebiasis. No vaccine is yet available for amoebiasis. Heparan Sulphate Binding Proteins (HSBPs) from E. histolytica were evaluated for immunogenicity and protective efficacy in a Guinea pig model. Animals were immunized subcutaneously with 30μg of HSBP by three weekly inoculations. The immunogenicity of HSBP was determined by antibody response (IgG, IgM and IgA), splenocyte proliferation assay and in vitro direct amoebicidal assay with splenic lymphocytes and monocytes from vaccinated and control animals. The efficacy of the vaccine was evaluated by challenge infection to vaccinated and control animals by intra-caecal inoculation of E. histolytica trophozoites and comparing gross and histopathological findings in caeca of these animals. HSBP was found to induce specific anti-amoebic response as seen by specific antibody production and direct amoebicidal activity of splenocytes. The vaccine also showed partial protection against challenge infection in vaccinated animals as shown by mild/absent lesions and histopathological findings. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of x-radiation to brain on cerebral glucose utilization in the rat.

PubMed

D'Aquino, S; Cicciarello, R; D'Avella, D; Mesiti, M; Albiero, F; Princi, P; Gagliardi, M E; Russi, E; D'Aquino, A

1990-01-01

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

Bariatric Radioembolization: A Pilot Study on Technical Feasibility and Safety in a Porcine Model.

PubMed

Pasciak, Alexander S; Bourgeois, Austin C; Paxton, Ben E; Nodit, Laurentia; Coan, Patricia N; Kraitchman, Dara; Stinnett, Sandra S; Patel, Vijay M; Fu, Yingli; Adams, Joleen K; Tolbert, M Katherine; Lux, Cassie N; Arepally, Aravind; Bradley, Yong C

2016-10-01

To evaluate feasibility of left gastric artery (LGA) yttrium-90 ((90)Y) radioembolization as potential treatment for obesity in a porcine model. This study included 8 young female pigs (12-13 weeks, 21.8-28.1 kg). Six animals received infusions of (90)Y resin microspheres (46.3-105.1 MBq) into the main LGA and the gastric artery arising from the splenic artery. Animal weight and serum ghrelin were measured before treatment and weekly thereafter. Animals were euthanized 69-74 days after treatment, and histologic analyses of mucosal integrity and ghrelin immunoreactive cell density were performed. Superficial mucosal ulcerations < 3.0 cm(2) were noted in 5 of 6 treated animals. Ghrelin immunoreactive cell density was significantly lower in treated versus untreated animals in the stomach fundus (13.5 vs 34.8, P < .05) and stomach body (11.2 vs 19.8, P < .05). Treated animals gained less weight than untreated animals over the study duration (40.2 kg ± 5.4 vs 54.7 kg ± 6.5, P = .053). Average fundic parietal area (165 cm(2) vs 282 cm(2), P = .067) and average stomach weight (297.2 g vs 397.0 g, P = .067) were decreased in treated versus untreated animals. Trichrome staining revealed significantly more fibrosis in treatment animals compared with control animals (13.0 vs 8.6, P < .05). No significant differences were identified in plasma ghrelin concentrations (P = .24). LGA (90)Y radioembolization is promising as a potential treatment for obesity. A larger preclinical study is needed to evaluate the safety and efficacy of this procedure further. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-07-01

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

[Influence of feeding rumen-protected choline to transition dairy cows. Part 2: Health and reproduction].

PubMed

Furken, C; Hoedemaker, M

2014-01-01

To determine the effects of rumen-protected choline (RPC) on health and reproduction in dairy cows. A total of 298 primi- and multiparous German Holstein cows of a high-production dairy herd (average daily milk yield: 32 l) were assigned randomly to a control or treatment group and were hand fed with 0 or 60 g/d of RPC as ReaShure®, respectively, from 21 days before expected calving to 21 days post partum (p. p.) as a top dressing. Health data was analyzed for the incidence of fever within the first 10 days in milk (DIM) as well as the incidence of diseases and the culling rate within the first 200 DIM. Reproduction data were evaluated in terms of the calving data, uterine involution on days 10, 21 and 42 p. p., uterine cytology at day 42 p. p., progesterone concentrations during weeks 3 and 5 p. p. and certain fertility measures. In the statistical analysis, it was differentiated between the control and treatment groups and between primi- and multiparous animals, and their interactions were analyzed. The treatment group had less cows with subclinical endometritis, higher sickness rates after day 100 p. p., lower numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the control group (p  <  0.05). Primipara in contrast to multipara had fever more frequently, higher rates of subclinical ketosis p. p., metritis and lameness, higher numbers of sick cows in the first 30 DIM, higher rates of stillbirths and dystocia, showed impaired involution of the uterus on day 10 p. p., fewer animals were cyclic during week 5 p. p. and less animals were culled (p < 0.05). Statistically significant interactions indicated that more heifers of the treatment group were lame, more heifers of the control group developed fever and subclinical endometritis, cows of the treatment group suffered more metritis and were sick more often in the first 30 DIM, and cows of the control group had more dystocia (p < 0.05). Overall, supplementing RPC had only minor effects on the health status and reproduction. Further research in other dairy herds should focus on this topic.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-03-01

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

The effect of methamphetamine on an animal model of erectile function.

PubMed

Tar, M T; Martinez, L R; Nosanchuk, J D; Davies, K P

2014-07-01

In the US methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies, we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine [2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)] i.p. daily for 3 weeks and erectile function compared with untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies, we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6 mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals, the ICP/BP ratio following 4 and 6 mA stimulation decreased by approximately 50% compared with untreated animals and erectile dysfunction (ED) was also reversed by tadalafil. Overall, our data suggest that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report ED associated with therapeutics-containing methamphetamine or amphetamine with PDE5i. © 2014 American Society of Andrology and European Academy of Andrology.

Enhancing emotion recognition in children with autism spectrum conditions: an intervention using animated vehicles with real emotional faces.

PubMed

Golan, Ofer; Ashwin, Emma; Granader, Yael; McClintock, Suzy; Day, Kate; Leggett, Victoria; Baron-Cohen, Simon

2010-03-01

This study evaluated The Transporters, an animated series designed to enhance emotion comprehension in children with autism spectrum conditions (ASC). n = 20 children with ASC (aged 4-7) watched The Transporters everyday for 4 weeks. Participants were tested before and after intervention on emotional vocabulary and emotion recognition at three levels of generalization. Two matched control groups of children (ASC group, n = 18 and typically developing group, n = 18) were also assessed twice without any intervention. The intervention group improved significantly more than the clinical control group on all task levels, performing comparably to typical controls at Time 2. We conclude that using The Transporters significantly improves emotion recognition in children with ASC. Future research should evaluate the series' effectiveness with lower-functioning individuals.

Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage

PubMed Central

2014-01-01

Introduction Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. Methods sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. Results All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Conclusions Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced subchondral sclerosis, synovial macrophage activation, and osteophyte formation. PMID:24472689

Effects of Reducing Antimicrobial Use and Applying a Cleaning and Disinfection Program in Veal Calf Farming: Experiences from an Intervention Study to Control Livestock-Associated MRSA

PubMed Central

Bos, Marian E. H.; Verstappen, Koen M.; Van Cleef, Brigitte A. G. L.; Kluytmans, Jan A. J. W.; Wagenaar, Jaap A.; Heederik, Dick J. J.

2015-01-01

With the ultimate aim of containing the emergence of resistant bacteria, a Dutch policy was set in place in 2010 promoting a reduction of antimicrobial use (AMU) in food-producing animals. In this context, a study evaluated strategies to curb livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA). Fifty-one veal calf farms were assigned to one of 3 study arms: RAB farms reducing antimicrobials by protocol; RAB-CD farms reducing antimicrobials by protocol and applying a cleaning and disinfection program; and Control farms without interventions. MRSA carriage was tested in week 0 and week 12 of 2 consecutive production cycles in farmers, family members and veal calves. Interventions were validated and a cyclic rise in MRSA-prevalence in animals was shown with a more moderate increase in RAB farms. Prevalence in humans declined parallel over time in the study arms but RAB farms were at the lowest MRSA levels from the beginning of the study. In RAB-CD farms, human and animal prevalence did not differ from Control farms and MRSA air loads were significantly higher than in the other study arms. Mimicking the national trend, an overall AMU decrease (daily dosages per animal per cycle (DDDA/C)) was observed over 4 pre-study and the 2 study cycles; this trend did not have a significant effect on a set of evaluated farm technical parameters. AMU was positively associated with MRSA across study arms (ORs per 10 DDDA/C increase = 1.26 for both humans (p = 0.07) and animals (p = 0.12 in first cycle)). These results suggest that AMU reduction might be a good strategy for curbing MRSA in veal calf farming, however the specific cleaning and disinfecting program in RAB-CD farms was not effective. The drop in MRSA prevalence in people during the study could be attributed to the observed long-term AMU decreasing trend. PMID:26305895

Effects of Reducing Antimicrobial Use and Applying a Cleaning and Disinfection Program in Veal Calf Farming: Experiences from an Intervention Study to Control Livestock-Associated MRSA.

PubMed

Dorado-García, Alejandro; Graveland, Haitske; Bos, Marian E H; Verstappen, Koen M; Van Cleef, Brigitte A G L; Kluytmans, Jan A J W; Wagenaar, Jaap A; Heederik, Dick J J

2015-01-01

With the ultimate aim of containing the emergence of resistant bacteria, a Dutch policy was set in place in 2010 promoting a reduction of antimicrobial use (AMU) in food-producing animals. In this context, a study evaluated strategies to curb livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA). Fifty-one veal calf farms were assigned to one of 3 study arms: RAB farms reducing antimicrobials by protocol; RAB-CD farms reducing antimicrobials by protocol and applying a cleaning and disinfection program; and Control farms without interventions. MRSA carriage was tested in week 0 and week 12 of 2 consecutive production cycles in farmers, family members and veal calves. Interventions were validated and a cyclic rise in MRSA-prevalence in animals was shown with a more moderate increase in RAB farms. Prevalence in humans declined parallel over time in the study arms but RAB farms were at the lowest MRSA levels from the beginning of the study. In RAB-CD farms, human and animal prevalence did not differ from Control farms and MRSA air loads were significantly higher than in the other study arms. Mimicking the national trend, an overall AMU decrease (daily dosages per animal per cycle (DDDA/C)) was observed over 4 pre-study and the 2 study cycles; this trend did not have a significant effect on a set of evaluated farm technical parameters. AMU was positively associated with MRSA across study arms (ORs per 10 DDDA/C increase = 1.26 for both humans (p = 0.07) and animals (p = 0.12 in first cycle)). These results suggest that AMU reduction might be a good strategy for curbing MRSA in veal calf farming, however the specific cleaning and disinfecting program in RAB-CD farms was not effective. The drop in MRSA prevalence in people during the study could be attributed to the observed long-term AMU decreasing trend.

Body mass, composition, and food intake in rabbits during altered acceleration fields

NASA Technical Reports Server (NTRS)

Katovich, M. J.; Smith, A. H.

1978-01-01

Mature male Polish rabbits were subjected to varying gravitational fields in an animal centrifuge in order to evaluate the effects of acceleration and deacceleration on body mass, body composition, and food intake. The acceleration field intensity was increased by 0.25-G increments to a maximum of 2.5 G at intervals which permitted physiological adaptation at each field. Control animals of the same age were maintained at earth gravity under identical conditions of constant-light environment at a room temperature of 23 + or - 5 C. It is shown that increasing the acceleration-field intensity leads to a decrease in body mass. The regulated nature of this decreased body mass is tested by the response to an additional three-day fasting of animals adapted physiologically to 2.5 G. Ad libitum food intake per kg body mass per day tends to increase in chronically accelerated animals above 1.75 G. Increase in water content in centrifuged animals after physiological adaptation to 2.5 G is the result of decreasing body fat. Body mass and food intake returned to the precentrifuged levels of control animals within six weeks after cessation of centrifugation.

A randomized controlled trial of dexamethasone as an adjunctive therapy to propylene glycol for treatment of hyperketonemia in postpartum dairy cattle.

PubMed

Tatone, Elise H; Duffield, Todd F; Capel, Michael B; DeVries, Trevor J; LeBlanc, Stephen J; Gordon, Jessica L

2016-11-01

Treatment of hyperketonemia with oral propylene glycol has proven efficacy but the cure rate remains moderate. Dexamethasone has long been suggested as a treatment for hyperketonemia, even though evidence of its efficacy is contradictory. The objective of this randomized controlled trial was to evaluate the effect of adding a single intramuscular injection of 20mg of dexamethasone to oral propylene glycol therapy for hyperketonemia [blood β-hydroxybutyrate (BHB) ≥1.2mmol/L]. All cows between 3 and 16d in milk on 4 dairy farms in New York State were tested once weekly for hyperketonemia using a handheld ketone meter. All enrolled animals received 312g (300mL) of propylene glycol orally once daily for 4d and either a single injection of dexamethasone or an equivalent volume of sterile saline. A total of 509 animals were enrolled, with 254 and 255 in the placebo and dexamethasone groups, respectively. Treatment with dexamethasone decreased the odds of being hyperketonemic in the second week posttreatment; however, the odds of hyperketonemia in the first week posttreatment only decreased in those animals that were treated at a BHB blood concentration between 1.2 and 1.5mmol/L. For the 8% of cows with blood BHB >3.2mmol/L at enrollment, receiving dexamethasone increased the odds of being hyperketonemic the following week. We detected no difference between treatment groups in the odds of postpartum disease or in milk production. For cows with initial BHB of 1.2 to 1.5mmol/L, treatment with dexamethasone tended to reduce the odds of pregnancy at first insemination. Based on the small and conditional benefits of dexamethasone and a lack of difference in milk yield or disease incidence, we do not recommend the use of dexamethasone to treat hyperketonemia. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Altered defaecatory behaviour and faecal incontinence in a video-tracked animal model of pudendal neuropathy.

PubMed

Devane, L A; Lucking, E; Evers, J; Buffini, M; Scott, S M; Knowles, C H; O'Connell, P R; Jones, J F X

2017-05-01

The aim was to develop a behavioural animal model of faecal continence and assess the effect of retro-uterine balloon inflation (RBI) injury. RBI in the rat causes pudendal neuropathy, a risk factor for obstetric related faecal incontinence in humans. Video-tracking of healthy rats (n = 12) in a cage containing a latrine box was used to monitor their defaecatory behaviour index (DBI) over 2 weeks. The DBI (range 0-1) was devised by dividing the defaecation rate (pellets per hour) outside the latrine by that of the whole cage. A score of 0 indicates all pellets were deposited in the latrine. Subsequently, the effects of RBI (n = 19), sham surgery (n = 4) and colostomy (n = 2) were determined by monitoring the DBI for 2 weeks preoperatively and 3 weeks postoperatively. The DBI for healthy rats was 0.1 ± 0.03 with no significant change over 2 weeks (P = 0.71). In the RBI group, 13 of 19 rats (68%) showed no significant change in DBI postoperatively (0.08 ±  -0.05 vs 0.11 ±  -0.07) while in six rats the DBI increased from 0.16 ±  -0.09 to 0.46 ± 0.23. The negative control, sham surgery, did not significantly affect the DBI (0.09 ± 0.06 vs 0.08 ± 0.04, P = 0.14). The positive control, colostomy, increased the DBI from 0.26 ± 0.03 to 0.86 ± 0.08. This is the first study showing a quantifiable change in defaecatory behaviour following injury in an animal model. This model of pudendal neuropathy affects continence in 32% of rats and provides a basis for research on interventions for incontinence. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Achilles tendinosis – a morphometrical study in a rat model

PubMed Central

Silva, Rafael Duarte; Glazebrook, Mark Anthony; Campos, Vinicius Castro; Vasconcelos, Anilton Cesar

2011-01-01

This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis. PMID:22076169

Blunted sympathoinhibitory responses in obesity-related hypertension are due to aberrant central but not peripheral signalling mechanisms

PubMed Central

How, Jackie M Y; Wardak, Suhail A; Ameer, Shaik I; Davey, Rachel A; Sartor, Daniela M

2014-01-01

The gut hormone cholecystokinin (CCK) acts at subdiaphragmatic vagal afferents to induce renal and splanchnic sympathoinhibition and vasodilatation, via reflex inhibition of a subclass of cardiovascular-controlling neurons in the rostroventrolateral medulla (RVLM). These sympathoinhibitory and vasodilator responses are blunted in obese, hypertensive rats and our aim in the present study was to determine whether this is attributable to (i) altered sensitivity of presympathetic vasomotor RVLM neurons, and (ii) aberrant peripheral or central signalling mechanisms. Using a diet-induced obesity model, male Sprague–Dawley rats exhibited either an obesity-prone (OP) or obesity-resistant (OR) phenotype when placed on a medium high fat diet for 13–15 weeks; control animals were placed on a low fat diet. OP animals had elevated resting arterial pressure compared to OR/control animals (P < 0.05). Barosensitivity of RVLM neurons was significantly attenuated in OP animals (P < 0.05), suggesting altered baroreflex gain. CCK induced inhibitory responses in RVLM neurons of OR/control animals but not OP animals. Subdiaphragmatic vagal nerve responsiveness to CCK and CCK1 receptor mRNA expression in nodose ganglia did not differ between the groups, but CCK induced significantly less Fos-like immunoreactivity in both the nucleus of the solitary tract and the caudal ventrolateral medulla of OP animals compared to controls (P < 0.05). These results suggest that blunted sympathoinhibitory and vasodilator responses in obesity-related hypertension are due to alterations in RVLM neuronal responses, resulting from aberrant central but not peripheral signalling mechanisms. In obesity, blunted sympathoinhibitory mechanisms may lead to increased regional vascular resistance and contribute to the development of hypertension. PMID:24492842

Placement of a covered polyester stent prevents complications from a colorectal anastomotic leak and supports healing: randomized controlled trial in a large animal model.

PubMed

Tsereteli, Zurab; Sporn, Emanuel; Geiger, Timothy M; Cleveland, Dava; Frazier, Shellaine; Rawlings, Arthur; Bachman, Sharon L; Miedema, Brent W; Thaler, Klaus

2008-11-01

Anastomotic leaks after colorectal operation continue to be a significant cause of morbidity. A covered endoluminal stent could seal a leak and eliminate the need for diversion. The aim of this study was to test the efficacy of a temporary covered stent to prevent leak related complications. Sixteen adult pigs (80-120 lbs) underwent open transection of the rectosigmoid followed by anastomosis with a circular stapler. Eight animals (study group) underwent endoscopic placement of a 21-mm covered polyester stent. Eight control group animals were left without stents. In all animals, a 2-cm leak was created along the anterior portion of the anastomosis. The animals were killed after 2 weeks and evaluated for abdominal infection, fistulae, and adhesions. The anastomosis was excised and the following parameters were assessed by a pathologist blinded to treatment: mucosal interruption (mm), inflammatory response, collagen type I and III, granulation, and fibrosis (grade 0-4). Stents were spontaneously expelled between postoperative days 6 and 9. At necropsy, none of the animals in the study group had leak related complications, whereas in the control group, 5 (63%) developed intraabdominal infection (4 abscesses, 1 fistula) at the anastomosis (P = .002). Dense adhesions to the anastomosis were found in 7 (88%) control animals. On histology, anastomotic sites in the study group had significantly less mucosal interruption and granulation. Two pigs in the study group died on postoperative day 7, one due to evisceration and one from bladder necrosis. The mortality result is not different from controls (P = .47), both events seem to be unrelated to stent placement. Temporary placement of a covered polyester stent across a colorectal anastomosis prevents leak-related complications and supports the healing of anastomotic leaks.

Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep

PubMed Central

Gavidia, Cesar M.; Gonzalez, Armando E.; Barron, Eduardo A.; Ninaquispe, Berenice; Llamosas, Monica; Verastegui, Manuela R.; Robinson, Colin; Gilman, Robert H.

2010-01-01

Background Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep. Methodology/Principal Findings A randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. “Noninfective” sheep were those that had no viable PSCs; “low-medium infective” were those that had 1% to 60% PSC viability; and “high infective” were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either “noninfective” or “low-medium infective” sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% “noninfective” or “low-medium infective” for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05). Conclusions/Significance We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans. PMID:20186332

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures

PubMed Central

Wu, Yuhsin; Schomisch, Steve J.; Cipriano, Cassandra; Chak, Amitabh; Lash, Richard H.; Ponsky, Jeffrey L.

2015-01-01

Background Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Methods Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. Results The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Conclusions Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy. PMID:24100858

Evaluation of oxfendazole, praziquantel and albendazole against cystic echinococcosis: a randomized clinical trial in naturally infected sheep.

PubMed

Gavidia, Cesar M; Gonzalez, Armando E; Barron, Eduardo A; Ninaquispe, Berenice; Llamosas, Monica; Verastegui, Manuela R; Robinson, Colin; Gilman, Robert H

2010-02-23

Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep. A randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. "Noninfective" sheep were those that had no viable PSCs; "low-medium infective" were those that had 1% to 60% PSC viability; and "high infective" were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either "noninfective" or "low-medium infective" sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% "noninfective" or "low-medium infective" for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05). We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.

The effects of healing abutments of different size and anatomic shape placed immediately in extraction sockets on peri-implant hard and soft tissues. A pilot study in foxhound dogs.

PubMed

López-López, Patricia J; Mareque-Bueno, Javier; Boquete-Castro, Ana; Aguilar-Salvatierra Raya, Antonio; Martínez-González, José M; Calvo-Guirado, José L

2016-01-01

The aim of this animal study was to compare the effects of narrow, concave-straight and wide anatomic healing abutments on changes to soft tissues and crestal bone levels around implants immediately placed into extraction sockets in foxhound dogs. Forty-eight titanium implants (Bredent Medical GMBH, Germany) of the same dimensions were placed in six foxhound dogs. They were divided into two groups (n = 24): test (implants with anatomic abutment) and control (implants with concave-straight abutment). The implants were inserted randomly in the post extraction sockets of P2 , P3 , P4, and M1 bilaterally in six dogs. After eight and twelve weeks, the animals were sacrificed and samples extracted containing the implants and the surrounding soft and hard tissues. Soft tissue and crestal bone loss (CBL) were evaluated by histology and histomorphometry. All implants were clinically and histologically osseointegrated. Healing patterns were examined microscopically at eight and twelve weeks. After eight and twelve weeks, for hard tissues, the distance from the implant shoulder to the first bone-to-implant contact (IS-C) was higher for control group in the lingual aspect with statistical significance (P < 0.05). For soft tissues (STL), the distance from the top of the peri-implant mucosa to the apical portion of the junction epithelium (PM-Je) was significantly less on the lingual aspect in the test group (with wider abutment) at eight and twelve weeks (P < 0.05). The distance from the top of the apical portion of the junction epithelium to the first bone-to-implant contact (Je-C) was significantly higher in the test group (wider abutment) in the lingual aspect at eight and twelve weeks (P < 0.05). There was no connective tissue contact with any abutment surface. Within the limitations of this animal study, anatomic healing abutments protect soft and hard tissues and reduce crestal bone resorption compared with concave-straight healing abutments. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

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

Okura, Hanayuki; Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047; Saga, Ayami

Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion ofmore » the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.« less

Economic value of urea-treated straw fed to lactating buffaloes during the dry season in Nepal.

PubMed

Chemjong, P B

1991-08-01

An experiment was conducted to study the effects of feeding urea-treated rice straw to lactating buffaloes in the Koshi Hills. Six pairs of similar buffaloes on farms were selected. All were given a conventional diet based on rice straw for four weeks, then one of each pair was given 15 to 20 kg/day of urea-treated rice straw for a period of four weeks while the control group received untreated rice straw. In the final four week period all animals were given the conventional diet. Feeding straw treated with 4% urea increased the voluntary intake of straw by 25% and increased milk yield by 1.6 litres/day compared with buffaloes fed the conventional diet containing untreated straw. Milk production remained elevated after the four-week treatment period had finished. The results show that buffalo cows fed urea-treated straw achieved better weight gain, and milk yield increased significantly (P less than 0.01) compared with the control animals. During the treatment period the net benefit was 4.0 (i.e. US$1.16) Nepalese currency rupees (NCRs) per day and the incremental rate of return was 46 per cent. Moreover, in the four weeks following the treatment period the net benefit was 10.0 NCRs (i.e. US$0.40) per day. Ensiling rice straw with 4% urea can be recommended as a safe, economical and suitable method for improving the nutritional value of rice straw on small farms in Nepal thus increasing milk production and liveweight of lactating buffaloes. The practice of feeding urea-treated straw is economic for farmers during the dry season from January to April.(ABSTRACT TRUNCATED AT 250 WORDS)

Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model.

PubMed

Hussein, Mahmoud R; Ahmed, Omyma G; Hassan, Asmaa F; Ahmed, Marwa A

2007-02-01

Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptor-mediated effects. The clinical ramifications of these effects await further investigations.

Effect of vanadium on colonic aberrant crypt foci induced in rats by 1,2 Dimethyl hydrazine

PubMed Central

Kanna, P Suresh; Mahendrakumar, CB; Chakraborty, T; Hemalatha, P; Banerjee, Pratik; Chatterjee, M

2003-01-01

AIM: To investigate the chemo preventive effects of vanadium on rat colorectal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). METHODS: Male Sprague-Dawley Rats were randomly divided into four groups. Rats in Group A received saline vehicle alone for 16 weeks. Rats in Group B were given DMH injection once a week intraperitoneally for 16 weeks; rats in Group C, with the same DMH treatment as in the Group B, but received 0.5-ppm vanadium in the form ammonium monovanadate ad libitum in drinking water. Rats in the Group D received vanadium alone as in the Group C without DMH injection. RESULTS: Aberrant crypt foci (ACF) were formed in animals in DMH-treated groups at the end of week 16. Compared to DMH group, vanadium treated group had less ACF (P < 0.001). At the end of week 32, all rats in DMH group developed large intestinal tumors. Rats treated with vanadium contained significantly few colonic adenomas and carcinomas (P < 0.05) compared to rats administered DMH only. In addition, a significant reduction (P < 0.05) in colon tumor burden (sum of tumor sizes per animal) was also evident in animals of Group C when compared to those in rats of carcinogen control Group B. The results also showed that vanadium significantly lowered PCNA index in ACF (P < 0.005). Furthermore, vanadium supplementation also elevated liver GST and Cyt P-450 activities (P < 0.001 and P < 0.02, respectively). CONCLUSION: Vanadium in the form of ammonium monovanadate supplemented in drinking water ad libitum has been found to be highly effective in reducing tumor incidence and preneoplastic foci on DMH-induced colorectal carcinogenesis. These findings suggest that vanadium administration can suppress colon carcinogenesis in rats. PMID:12717849

The influence of sex and diet on the characteristics of hibernation in Syrian hamsters.

PubMed

Trefna, Marie; Goris, Maaike; Thissen, Cynthia M C; Reitsema, Vera A; Bruintjes, Jojanneke J; de Vrij, Edwin L; Bouma, Hjalmar R; Boerema, Ate S; Henning, Robert H

2017-07-01

Research on deep hibernators almost exclusively uses species captured from the wild or from local breeding. An exception is Syrian hamster (Mesocricetus auratus), the only standard laboratory animal showing deep hibernation. In deep hibernators, several factors influence hibernation quality, including body mass, sex and diet. We examined hibernation quality in commercially obtained Syrian hamsters in relation to body mass, sex and a diet enriched in polyunsaturated fatty acids. Animals (M/F:30/30, 12 weeks of age) were obtained from Harlan (IN, USA) and individually housed at 21 °C and L:D 14:10 until 20 weeks of age, followed by L:D 8:16 until 27 weeks. Then conditions were changed to 5 °C and L:D 0:24 for 9 weeks to induce hibernation. Movement was continuously monitored with passive infrared detectors. Hamsters were randomized to control diet or a diet 3× enriched in linoleic acid from 16 weeks of age. Hamsters showed a high rate of premature death (n = 24, 40%), both in animals that did and did not initiate torpor, which was unrelated to body weight, sex and diet. Time to death (31.7 ± 3.1 days, n = 12) or time to first torpor bout (36.6 ± 1.6 days, n = 12) was similar in prematurely deceased hamsters. Timing of induction of hibernation and duration of torpor and arousal was unaffected by body weight, sex or diet. Thus, commercially obtained Syrian hamsters subjected to winter conditions showed poor survival, irrespective of body weight, sex and diet. These factors also did not affect hibernation parameters. Possibly, long-term commercial breeding from a confined genetic background has selected against the hibernation trait.

The differential effects of chronic imipramine or citalopram administration on physiological and behavioral outcomes in naïve mice.

PubMed

Strekalova, Tatyana; Anthony, Daniel C; Dolgov, Oleg; Anokhin, Konstantin; Kubatiev, Aslan; Steinbusch, Harry M W; Schroeter, Careen

2013-05-15

Tricyclics and selective serotonin reuptake inhibitors (SSRIs) are probably the most widely employed reference antidepressants in animal studies on depression. Using imipramine and citalopram, we sought to assess which drug would be more appropriate as pharmacological reference in paradigms of depression in C57BL6N mice by measuring their effect on liquid consumption, home cage activity, body weight and long-term memory in naïve animals treated with each compound at generally used dose of 15 mg/kg/day. Continuous logging of home cage movement, weekly monitoring of vertical activity in a novel cage, and body weight was recorded during four-week treatment period and for four weeks after discontinuation of the antidepressant; sucrose preference was evaluated at weekly intervals during drug administration. A novel object recognition memory test was performed in mice treated the antidepressants for two weeks. Compared to control, imipramine-treated mice displayed increased sucrose and water intake, as well as enhanced home-cage and novelty exploration activities, and reduced body weight. Imipramine also impaired learning in the object recognition task, but citalopram diminished object exploration sufficiently to invalidate the test. Citalopram-treated animals demonstrated no changes in a sucrose test and had elevated body mass. Thus basic physiological and behavioral outcomes in naïve mice were significantly altered by the chronic administration of imipramine and, to a lesser extent, citalopram. As altered variables are crucial for the evaluation of antidepressant-like effects in mice, our data suggest that, at commonly used doses, both drugs must be applied in mouse models of depression with caution. Copyright © 2013 Elsevier B.V. All rights reserved.

Accumulation of cadmium in tissue and its effect on live performance

NASA Astrophysics Data System (ADS)

Akyolcu, M. C.; Ozcelik, D.; Dursun, S.; Toplan, S.; Kahraman, R.

2003-05-01

Heavy metal pollution has gained more importance for environment as a result of increased industrialization rate all over the world. In present study investigation of effects of cadmium on live-weight due to accumulation in different tissues that taken in food were aimed. For such a purpose after their birth for four weeks chickens were fed by Cd added fodder (25 mg Cd/kg as cadmium sulfate). At the end offour weeks feeding period the chickens were scaled and sacrificed. For tissue cadmium level measurements, liver, kidney, muscle and bone dissections were performed on both experimental and same age contrai group animals. The measurements were performed in atomic absorption spectrophotometer. At the end of evaluation of data it was observed that live mean weight of experimental group was significantly lower than that of control group animals (p < 0.001). On the other hand tissue cadmium concentrations of experimental group were found to be significantly higher than that of control group values. So accumulation of cadmium in tissue as a heavy metal may lead decreased rate of growth.

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.

Immunization of cattle against East Coast fever using Theileria parva (Marikebuni) and relaxation of tick control in North Rift, Kenya.

PubMed

Wanjohi, J M; Ngeranwa, J N; Rumberia, R M; Muraguri, G R; Mbogo, S K

2001-09-01

A total of 90 animals was immunized against East Coast fever (ECF) using Theileria parva (Marikebuni) stock on three large-scale farms in Kiminini Division, Trans-Nzoia District, North Rift, Kenya. Another 90 cattle served as non-immunized controls. Following immunization the number of cattle with significant indirect fluorescent antibody (IFA) titres increased from 43.9% to 84.4% and 6.7% of the cattle developed clinical ECF reactions. Two months after immunization, the immunized and non-immunized cattle were divided into two groups one of which was dipped every 3 weeks and the other dipped when total full body tick counts reached 100. All the animals were monitored for 51 weeks for incidences of ECF and other tick-borne diseases. Twenty-four cases of ECF were diagnosed among the non-immunized cattle compared to four cases among the immunized cattle; a difference that was significant (P > 0.05). There was no significant difference in the incidences of babesiosis and anaplasmosis between the immunized and non-immunized cattle.

Antiadhesive effect of polyurethane foam packing in the guinea pig middle ear.

PubMed

Choi, Cheol Hee; Jang, Chul Ho

2015-02-01

No significant subepithelial healing differences were found between Gelfoam and polyurethane foam (PUF). However, levels of hyperplasia of the mucosal lining and inflammation were lower with PUF packing. PUF packing is not feasible as a middle ear packing material for abraded mucosa. Further studies are required before clinical application. To date, there have been few reports on the antiadhesive effect of PUF as a middle ear packing. The purpose of this study was to investigate the antiadhesive effect of PUF soaked with saline in an animal model of mucosal trauma. Bioresorbable PUF soaked with saline was placed over abraded mucosa in the experimental group (n = 7), and compressed Gelfoam soaked with saline was placed in the control group (n = 7). After measurement of auditory brainstem responses (ABRs), the animals were sacrificed 3 weeks after packing placement for histological observation. The ABR results at postoperative week 3 showed no statistically significant difference between the preoperative and post-packing values. An adhesion pattern with subepithelial thickening was observed in the control group. Adhesion was not observed in the experimental group; however, subepithelial fibrous thickening was noted.

The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats.

PubMed

Makarchian, Hamid Reza; Kasraianfard, Amir; Ghaderzadeh, Pezhman; Javadi, Seyed Mohammad Reza; Ghorbanpoor, Manoochehr

2017-01-01

To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

Changes in the Influence of Alcohol-Paired Stimuli on Alcohol Seeking across Extended Training

PubMed Central

Corbit, Laura H.; Janak, Patricia H.

2016-01-01

Previous work has demonstrated that goal-directed control of alcohol-seeking and other drug-related behaviors is reduced following extended self-administration and drug exposure. Here, we examined how the magnitude of stimulus influences on responding changes across similar training and drug exposure. Rats self-administered alcohol or sucrose for 2 or 8 weeks. Previous work has shown that 8 weeks, but not 2 weeks of self-administration produces habitual alcohol seeking. Next, all animals received equivalent Pavlovian conditioning sessions where a discrete stimulus predicted the delivery of alcohol or sucrose. Finally, the impact of the stimuli on ongoing instrumental responding was examined in a Pavlovian–instrumental transfer (PIT) test. While a significant PIT effect was observed following 2 weeks of either alcohol or sucrose self-administration, the magnitude of this effect was greater following 8 weeks of training. The specificity of the PIT effect appeared unchanged by extended training. While it is well established that evaluation of the outcome of responding contributes less to behavioral control following extended training and/or drug exposure, our data indicate that reward–predictive stimuli have a stronger contribution to responding after extended training. Together, these findings provide insight into the factors that control behavior after extended drug use, which will be important for developing effective methods for controlling and ideally reducing these behaviors. PMID:27777560

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys.

PubMed

Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Fanales-Belasio, Emanuele; Moretti, Sonia; Sernicola, Leonardo; Cara, Andrea; Negri, Donatella R M; Buttò, Stefano; Fiorelli, Valeria; Tripiciano, Antonella; Scoglio, Arianna; Caputo, Antonella; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Ciccozzi, Massimo; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

2004-09-03

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

Eight Weeks of Cosmos caudatus (Ulam Raja) Supplementation Improves Glycemic Status in Patients with Type 2 Diabetes: A Randomized Controlled Trial

PubMed Central

Cheng, Shi-Hui; Ismail, Amin; Anthony, Joseph; Ng, Ooi Chuan; Hamid, Azizah Abdul; Barakatun-Nisak, Mohd Yusof

2015-01-01

Objectives. Optimizing glycemic control is crucial to prevent type 2 diabetes related complications. Cosmos caudatus is reported to have promising effect in improving plasma blood glucose in an animal model. However, its impact on human remains ambiguous. This study was carried out to evaluate the effectiveness of C. caudatus on glycemic status in patients with type 2 diabetes. Materials and Methods. In this randomized controlled trial with two-arm parallel-group design, a total of 101 subjects with type 2 diabetes were randomly allocated to diabetic-ulam or diabetic controls for eight weeks. Subjects in diabetic-ulam group consumed 15 g of C. caudatus daily for eight weeks while diabetic controls abstained from taking C. caudatus. Both groups received the standard lifestyle advice. Results. After 8 weeks of supplementation, C. caudatus significantly reduced serum insulin (−1.16 versus +3.91), reduced HOMA-IR (−1.09 versus +1.34), and increased QUICKI (+0.05 versus −0.03) in diabetic-ulam group compared with the diabetic controls. HbA1C level was improved although it is not statistically significant (−0.76% versus −0.37%). C. caudatus was safe to consume. Conclusions. C. caudatus supplementation significantly improves insulin resistance and insulin sensitivity in patients with type 2 diabetes. PMID:26713097

Urinary arsenic and porphyrin profile in C57BL/6J mice chronically exposed to monomethylarsonous acid (MMAIII) for two years.

PubMed

Krishnamohan, Manonmanii; Qi, Lixia; Lam, Paul K S; Moore, Michael R; Ng, Jack C

2007-10-01

Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMA(III)), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 microg/L arsenic as MMA(III)ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA(V) was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 microg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 microAs/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMA(V) and porphyrin profile can be used as an early warning biomarker for chronic MMA(III) exposure before the onset of cancer.

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

HOMO-AUTOPLASTIC SURGERY IN BURNS OF IRRADIATED ANIMALS

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

Khaydarov, A.Kh.; Galayko, S.M.; Levin, S.I.

1962-01-01

Twenty-six rabbits of about the same weight and age were subjected to charring burns on their backs (9 cm/sup 2/) The necrotic scab was removed at regular time intervals and an auto- or homograft was immediately transplanted into the opened wound. Twenty rabbits were subjected to repeated x irradiation (2 x 600 r). Penetrating radiation affected the recipient of the homograft, which, when transplanted during the height of radiation sickness dissolved rapidly. The healing process of autografts was slower in the irradiated animals than in the controls. Homografts transplanted from irradiated animals, 7 days after irradiation with 600 r, tomore » healthy animals, remained alive for a long time and the epithelization of the wound occurred after 4 to 5 weeks. (OTS)« less

Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination.

PubMed

Boyer, J D; Ugen, K E; Wang, B; Agadjanyan, M; Gilbert, L; Bagarazzi, M L; Chattergoon, M; Frost, P; Javadian, A; Williams, W V; Refaeli, Y; Ciccarelli, R B; McCallus, D; Coney, L; Weiner, D B

1997-05-01

Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark for the use of DNA vaccine technology for the production of protective immune responses.

Enrofloxacin and Macrolides Alone or in Combination with Rifampicin as Antimicrobial Treatment in a Bovine Model of Acute Chlamydia psittaci Infection

PubMed Central

Prohl, Annette; Lohr, Markus; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Schroedl, Wieland; Rothe, Michael; Schubert, Evelyn; Sachse, Konrad; Reinhold, Petra

2015-01-01

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6–8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e. cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks. PMID:25768665

A rationale for treating leg length discrepancy using photodynamic therapy

NASA Astrophysics Data System (ADS)

Bisland, Stuart K.; Johnson, Crystal; Diab, Mohammed; Wilson, Brian C.; Burch, Shane

2005-09-01

This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1α was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized effects on bone development that may be applicable to other related skeletal deformities.

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

PubMed

Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

2017-11-01

To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biochemical and histological responses of Rattus novergicus (Wistar) infected by Echinostoma paraensei (Trematoda: Echinostomatidae).

PubMed

Garcia, Juberlan S; Hooper, Cleber S; Simões, Raquel O; Dos Santos, Marcos Antônio J; Maldonado, Arnaldo; Pinheiro, Jairo

2011-05-31

Tests were performed to evaluate the biochemical alterations in Rattus norvegicus after infection by the intestinal trematode Echinostoma paraensei. The rodents received 150 metacercariae each, serum samples were collected and the parasite load was quantified weekly until the fifth week of infection. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), gamma-glutamyl transferase (GGT), bilirubin, glucose, total proteins and fractions and hepatic glycogen were determined. All the animals exposed to the metacercariae were infected in the first week and worms were recovered up to the third week after infection. The levels of AST, ALT, GGT, bilirubin and globulin rose in the first and/or second week and declined thereafter to levels near those of the control group. In contrast, the level of total proteins in the plasma fell significantly in the first week while the ALKP activity went down only in the fourth and fifth weeks in relation to the control group. There was no significant difference in the levels of albumin, glycogen and glucose. Infection by E. paraensei in R. norvegicus causes changes in the hepatic function, possibly resulting from the cholestasis produced by the partial obstruction of the bile duct by the helminths. Copyright © 2011 Elsevier B.V. All rights reserved.

Biocompatibility of single-walled carbon nanotube composites for bone regeneration.

PubMed

Gupta, A; Liberati, T A; Verhulst, S J; Main, B J; Roberts, M H; Potty, A G R; Pylawka, T K; El-Amin Iii, S F

2015-05-01

The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70-7. ©2015 The British Editorial Society of Bone & Joint Surgery.

Biocompatibility of single-walled carbon nanotube composites for bone regeneration

PubMed Central

Gupta, A.; Liberati, T. A.; Verhulst, S. J.; Main, B. J.; Roberts, M. H.; Potty, A. G. R.; Pylawka, T. K.; El-Amin III, S. F.

2015-01-01

Objectives The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. Results No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Conclusions Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70–7 PMID:25943595

Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

PubMed

Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

2014-09-24

The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid Hemorrhage: Choroidal Artery Vasospasm-Related Ependymal Cell Degeneration and Aqueductal Stenosis-First Experimental Study.

PubMed

Yolas, Coskun; Ozdemir, Nuriye Guzin; Kanat, Ayhan; Aydin, Mehmet Dumlu; Keles, Papatya; Kepoglu, Umit; Aydin, Nazan; Gundogdu, Cemal

2016-06-01

Hydrocephalus is a serious complication of subarachnoid hemorrhage (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH. Although various etiologic theories have been put forward, choroidal artery vasospasm-related ependymal desquamation and subependymal basal membrane rupture as mechanisms of aqueductal stenosis have not been suggested in the literature. This study was conducted on 26 hybrid rabbits. Five rabbits were placed in a control group, 5 were placed in a sham group, and the remaining rabbits (n = 16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH group died. The other 21 animals were decapitated after the 4-week follow-up period. Choroidal artery changes resulting from vasospasm, aqueduct volume, ependymal cell density, and Evans index values of brain ventricles were obtained and compared statistically. Mean aqueduct volume was 1.137 mm(3) ± 0.096, normal ependymal cell density was 4560/mm(2) ± 745, and Evans index was 0.32 ± 0.05 in control animals (n = 5); these values were 1.247 mm(3) ± 0.112, 3568/mm(2) ± 612, and 0.34 ± 0.15 in sham animals (n = 5); 1.676 mm(3) ± 0.123, 2923/mm(2) ± 591, and 0.43 ± 0.09 in animals without aqueductal stenosis (n = 5); and 0.650 mm(3) ± 0.011, 1234/mm(2) ± 498, and 0.60 ± 0.18 in animals with severe aqueductal stenosis (n = 6). The choroidal vasospasm index values were 1.160 ± 0.040 in the control group, 1.150 ± 0.175 in the sham group, 1.760 ± 0.125 in the nonstenotic group, and 2.262 ± 0.160 in the stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and choroidal artery vasospasm index values were statistically significantly different between groups (P < 0.05). Ependymal cell desquamation and subependymal basal membrane destruction related to choroidal artery vasospasm may lead to aqueductal stenosis and hydrocephalus after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Motility and fertility of boar semen after liquid preservation at 5°C for more than 2 weeks.

PubMed

Namula, Zhao; Sato, Yoko; Kodama, Risa; Morinaga, Kouta; Luu, Vien Viet; Taniguchi, Masayasu; Nakai, Michiko; Tanihara, Fuminori; Kikuchi, Kazuhiro; Nagai, Takashi; Otoi, Takeshige

2013-08-01

This study investigated the effects of skim milk on the quality and fertility of boar spermatozoa under long-term chilled preservation. Semen samples were stored in Modena solution supplemented with 0 (control) to 50 mg/mL skim milk at 5°C for 4 weeks; spermatozoa stored with 7.5 and 15 mg/mL of skim milk (7.5-SM and 15-SM groups, respectively) exhibited significantly higher motility indices than those of the control group up to 3 weeks (P < 0.05), and the 7.5-SM group showed improved motility indices even after 4 weeks (P < 0.05). In vitro fertilization using spermatozoa in the 7.5-SM and 15-SM groups stored at 5°C for 2 weeks showed significantly higher fertilization rates of spermatozoa and the development rates to blastocyst than the control group (P < 0.05), and the 7.5-SM group showed similar rates of fertilization and blastocyst formation in the fresh non-stored spermatozoa group. After artificial insemination using spermatozoa stored for 2 weeks in the 7.5-SM group, healthy piglets were obtained. Boar spermatozoa can be stored at 5°C in a Modena solution containing skim milk. Supplementation of 7.5 mg/mL skim milk improves boar spermatozoa motility and fertility even after liquid preservation at 5°C for 2 weeks. © 2013 Japanese Society of Animal Science.

Subcutaneous administration of a 10-fold-lower dose of a commercial human tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guerin Danish, induced levels of protection against bovine tuberculosis and responses in the tuberculin intradermal test similar to those induced by a standard cattle dose.

PubMed

Buddle, Bryce M; Hewinson, R Glyn; Vordermeier, H Martin; Wedlock, D Neil

2013-10-01

Vaccination of cattle with a commercial human tuberculosis (TB) vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG) Danish, at a dose equivalent to 5 human doses of BCG has protected these animals against TB in field and experimental trials. There is interest in determining whether a 10-fold-lower dose could still protect cattle but not induce a tuberculin intradermal test response. Two groups of calves (n = 9/group) were vaccinated subcutaneously with a lyophilized BCG Danish vaccine containing either 0.5 (1 × 10(5) to 4 × 10(5) CFU) or 5 (1 × 10(6) to 4 × 10(6) CFU) human doses of BCG Danish, with an additional group of 10 calves serving as nonvaccinated controls. Fifteen weeks after vaccination, these animals were challenged intratracheally with 5 × 10(3) CFU of virulent M. bovis and another 15 weeks later were slaughtered and examined for the presence of tuberculous lesions. Vaccination of the calves with either 0.5 or 5 equivalent human doses of BCG Danish induced similar levels of protection against challenge with M. bovis, with both groups showing significant reductions in the pathological and microbiological parameters compared to those for the the control group (P < 0.05). Vaccination with either of the two BCG doses induced similar numbers of animals responding to the tuberculin intradermal test at 11 weeks postvaccination. Vaccination with a 0.5 equivalent human dose of a commercial lyophilized BCG vaccine can protect cattle against challenge with M. bovis.

The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking

PubMed Central

Hall, Brandon J.; Pearson, Laura S.; Terry, Alvin V.; Buccafusco, Jerry J.

2011-01-01

In this study, the use-dependent, nicotinic receptor antagonist bis (2, 2, 6, 6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was evaluated for its ability to attenuate the adverse consequences associated with morphine in rats in all three phases of an abstinence model of drug seeking: self-administration, acute withdrawal, and delayed test of drug seeking. Rats were allowed to self-administer morphine (FR1 schedule) with an active response lever, on a 24hr basis inside operant chambers, for 14 days. Each rat was subsequently evaluated for stereotypical behaviors associated with spontaneous morphine withdrawal. Rats were then placed in standard housing cages for a six week period of protracted abstinence from morphine. After this period, each rat was placed back into its respective operant chamber for a 14 day assessment of unrewarded drug seeking responses. BTMPS was administered to the animals in all three clinically relevant phases in three separate sets of experiments. BTMPS treatment during the self-administration phase resulted in up to a 34% reduction of lever responses to morphine when compared to vehicle treated control animals, as well as a 32% reduction in the dose of morphine self-administered. When given during self-administration and acute withdrawal, BTMPS treatment decreased acute withdrawal symptoms (up to 64%) of morphine use and reduced (up to 45%) drug seeking responses after six weeks of protracted withdrawal compared to control animals. BTMPS treatment after six weeks of abstinence from morphine had no effect. These results offer insight into the role of central cholinergic receptors in the onset and maintenance of drug addiction. PMID:21651919

Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection.

PubMed

Fujimoto, Ai; Uraoka, Toshio; Nishizawa, Toshihiro; Shimoda, Masayuki; Goto, Osamu; Ochiai, Yasutoshi; Maehata, Tadateru; Akimoto, Teppei; Mitsunaga, Yutaka; Sasaki, Motoki; Yamamoto, Hiroyuki; Yahagi, Naohisa

2018-04-01

Rebamipide is administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model. An endoscopist blinded to the test agents performed ESDs of hypothetical 30 mm lesions using a 2% rebamipide solution at 2 sites (rebamipide group) and a saline solution at 2 other sites (control group) in the stomachs of 8 pigs. The technical outcomes were compared between the 2 groups. The gastric ulcer stages were evaluated by endoscopy once weekly for 4 weeks after the ESD to determine the healing score (1-6). The pigs were killed at 1 week (n = 2), 2 weeks (n = 2), and 4 weeks (n = 4) after the ESD for pathologic evaluation of ESD-induced ulcers and scarring. There were no significant differences in any of the technical outcomes between the 2 groups, and no adverse events related to the ESD in any of the animals. The healing score was significantly higher in the rebamipide group than in the control group at 2 weeks (P = .027), 3 weeks (P = .034), and 4 weeks (P = .012). In the histopathologic assessment, fibrosis was significantly less extensive in the rebamipide group than in the control group at 2 weeks (P = .02) and 4 weeks (P = .04). The rebamipide solution appeared to promote both the speed and quality of healing of ESD-induced ulcers by suppressing fibrosis. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

PubMed Central

Melnikovova, Ingrid; Fait, Tomas; Kolarova, Michaela; Fernandez, Eloy C.

2015-01-01

Background/Aims. Products of Lepidium meyenii Walp. (maca) are touted worldwide as an alimentary supplement to enhance fertility and restore hormonal balance. Enhancing properties of maca on semen parameters in animals were previously reported by various authors, but we present to the best of our knowledge the first double-blind, randomized, placebo-controlled pilot trial in men. The aim of this study was to evaluate the effects of maca on semen parameters and serum hormone levels in healthy adult men. Methods. A group of 20 volunteers aged 20–40 years was supplied by milled hypocotyl of maca or placebo (1.75 g/day) for 12 weeks. Negative controls of semen were compared to the samples after 6 and 12 weeks of maca administration; negative blood controls were compared to the samples after 12 weeks of treatment. Results. Sperm concentration and motility showed rising trends compared to placebo even though levels of hormones did not change significantly after 12 weeks of trial. Conclusion. Our results indicate that maca possesses fertility enhancing properties in men. As long as men prefer to use alimentary supplement to enhance fertility rather than prescribed medication or any medical intervention, it is worth continuing to assess its possible benefits. PMID:26421049

Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

PubMed

Melnikovova, Ingrid; Fait, Tomas; Kolarova, Michaela; Fernandez, Eloy C; Milella, Luigi

2015-01-01

Background/Aims. Products of Lepidium meyenii Walp. (maca) are touted worldwide as an alimentary supplement to enhance fertility and restore hormonal balance. Enhancing properties of maca on semen parameters in animals were previously reported by various authors, but we present to the best of our knowledge the first double-blind, randomized, placebo-controlled pilot trial in men. The aim of this study was to evaluate the effects of maca on semen parameters and serum hormone levels in healthy adult men. Methods. A group of 20 volunteers aged 20-40 years was supplied by milled hypocotyl of maca or placebo (1.75 g/day) for 12 weeks. Negative controls of semen were compared to the samples after 6 and 12 weeks of maca administration; negative blood controls were compared to the samples after 12 weeks of treatment. Results. Sperm concentration and motility showed rising trends compared to placebo even though levels of hormones did not change significantly after 12 weeks of trial. Conclusion. Our results indicate that maca possesses fertility enhancing properties in men. As long as men prefer to use alimentary supplement to enhance fertility rather than prescribed medication or any medical intervention, it is worth continuing to assess its possible benefits.

Swimming exercise enhances the hippocampal antioxidant status of female Wistar rats.

PubMed

Stone, Vinícius; Kudo, Karen Yurika; Marcelino, Thiago Beltram; August, Pauline Maciel; Matté, Cristiane

2015-05-01

Moderate exercise is known to have health benefits, while both sedentarism and strenuous exercise have pro-oxidant effects. In this study, we assessed the effect of moderate exercise on the antioxidant homeostasis of rats' hippocampi. Female Wistar rats were submitted to a 30-minute swimming protocol on 5 days a week, for 4 weeks. Control rats were immersed in water and carefully dried. Production of hippocampal reactive species, activity of antioxidant enzymes, and glutathione levels in these animals were determined up to 30 days after completion of the 4-week protocol. Production of reactive species and hippocampal glutathione levels were increased 1 day after completion of the 4-week protocol, and returned to control levels after 7 days. Antioxidant enzyme activities were increased both 1 day (catalase) and 7 days (superoxide dismutase and glutathione peroxidase) after completion of the protocol. Thirty days after completion of the protocol, none of the antioxidant parameters evaluated differed from those of controls. Our results reinforce the benefits of aerobic exercise, which include positive modulation of antioxidant homeostasis in the hippocampi. The effects of exercise are not permanent; rather, an exercise regimen must be continued in order to maintain the neurometabolic adaptations.

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.

Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

PubMed

Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

2017-02-14

Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

PubMed Central

Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

2016-01-01

Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal. PMID:26962395

Memory Deficit Recovery after Chronic Vanadium Exposure in Mice.

PubMed

Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

2016-01-01

Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

NTP Studies of Magnetic Field Promotion (DMBA Initiation) in Female Sprague-Dawley Rats (Whole-body Exposure/Gavage Studies).

PubMed

1999-08-01

Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus, the potential for human exposure is high. These elec-tric and magnetic fields are predominantly of low fre-quency (60 Hz in the United States and 50 Hz in Europe) and generally of low intensity. Because some epidemiology studies and initiation/promotion studies in rats have suggested a potential for increased breast cancer rates with increasing magnetic field exposure, the ability of 50- and 60-Hz magnetic fields to pro-mote mammary gland tumors initiated by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) was examined in female Sprague-Dawley rats in 13- and 26-week whole-body exposure studies. Additional animals were evaluated for changes in pineal gland and serum melatonin concentrations. FIRST 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 20 mg DMBA (four weekly gavage doses of 5 mg in sesame oil) and exposed to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 rats administered 20 mg DMBA served as DMBA controls. A group of 100 vehicle control rats was administered only sesame oil on the same schedule. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All vehicle control rats survived to the end of the study. Of the animals administered 20 mg DMBA, 6 rats in the DMBA control group, 13 in the DMBA/1 G 50-Hz group, eight in the DMBA/5 G 50-Hz group, and five in the DMBA/1 G 60-Hz group died or were removed from the study prior to the final necropsy. Final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/1 G 60-Hz groups and the mean body weight gain of the DMBA/5 G 50-Hz group were slightly greater than those of the DMBA control group. Clinical findings including torso masses and ulcers (on the mammary masses) were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. SECOND 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 8 mg DMBA (four weekly gavage doses of 2 mg in sesame oil) and exposed to 1 G 50-Hz or 5 G 50-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 female rats administered 8 mg DMBA served as DMBA controls. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. Except for one rat in the DMBA/5 G 50-Hz group, all rats survived until the end of the study. Final mean body weights of DMBA/magnetic field groups were similar to those of the DMBA control group. Clinical findings including torso masses and ulcers were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. 26-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were administered 10 mg DMBA (in sesame oil) by gavage followed by exposure to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 26 weeks. A group of 100 female rats administered 10 mg DMBA served as DMBA controls. Another 100 vehicle control rats were administered only sesame oil. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All rats in the vehicle control group survived until the end of the study. Twelve rats in the DMBA control group, 15 in the DMBA/1 G 50-Hz group, 9 in the DMBA/5 G 50-Hz group, and six in the DMBA/1 G 60-Hz group died or were removed during the study. The final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/5 G 50-Hz groups were significantly greater than those of the DMBA control group. Clinical findings including torso masses, abscesses, and ulcers were attributed to DMBA administration. The pineal gland melatonin concentrations of DMBA/5 G 50-Hz and DMBA/1 G 60-Hz rats were significantly greater than that of the DMBA controls at week 12; however, these data were highly variable between individual animals within each group. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA controls. The incidences of mammary gland carci-noma (including multiple) in the DMBA/1 G 60-Hz group were significantly decreased relative to the DMBA control group. CONCLUSIONS: In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 5 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. The prevalence and multiplicity of mammary gland carcinomas in all DMBA groups limited the ability of this assay to detect a promoting effect of magnetic fields. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 2 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by a single 10 mg DMBA dose at 50 days of age and then exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 26 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms.

Reprint of: From the 90׳s to now: A brief historical perspective on more than two decades of estrogen neuroprotection.

PubMed

Engler-Chiurazzi, E B; Singh, M; Simpkins, J W

2016-08-15

Historical perspective abstract:From the 90׳s to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90׳s, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer׳s Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen׳s neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be among these. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats: We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-βE2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions. ChAT activity was decreased in the hippocampus but not the frontal cortex of 5-week OVX animals. E2 replacement resulted in a reversal of this effect. At the 28-week time period, an unexpected decrease in ChAT activity was observed across all treatment groups. Interestingly, E2-pellet animals demonstrated the least severe decline in ChAT. This phenomenon was most evident in the frontal cortex where ChAT decreased by 61 and 56% in INTACT and OVX animals, respectively, whereas the decline in E2-pellet animals was only 16% over the same time period, suggesting a previously unreported cytoprotective effect of E2. Taken together, these findings demonstrate important effects of estrogens on cholinergic neurons and support the potential use of estrogen therapy in treatment of dementias in postmenopausal women. © 1994. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

From the 90's to now: A brief historical perspective on more than two decades of estrogen neuroprotection.

PubMed

Engler-Chiurazzi, E B; Singh, M; Simpkins, J W

2016-02-15

Historical perspective abstract:From the 90's to now: a historical perspective on more than two decades of estrogen neuroprotection: In the early 90's, estrogens were known to exert organizational and activational effects on reproductive tissues and sexual behavior. As well, the role of sex and gonadal hormones in altering the risk for developing Alzheimer's Disease (AD) was only beginning to be elucidated. Preliminary investigations suggested that estrogen-containing therapies typically given for the management of disruptive menopausal symptoms could reduce AD risk, attenuate disease-associated cognitive deficits, and modulate brain substrates known to be dysregulated by the condition, such as the cholingeric system. The findings from our seminal paper demonstrating cognitive benefits and cholinergic impacts with exogenous estrogen treatment in a rodent model of surgical hormone depletion provided initial support for use of estrogen-containing therapies as a treatment for age-related brain disorders. We then went on to demonstrate neuroprotective actions of estrogen in several other in vivo and in vitro models of neurological challenge, including stroke and AD. Further, our findings of the chemical structure requirements for estrogen's neuroprotective effects identified a novel approach for optimizing future estrogen-containing hormone therapy options. These early efforts laid the groundwork for later, large-scale clinical investigations into the potential of estrogen-based menopausal hormone therapies for the prevention of a variety of age-related disorders. Although findings of these studies were equivocal, the neuroprotective actions of estrogen, and specifically 17β-estradiol, identified by early investigations, remain well-documented. Future development of interventions that optimize cognitive aging are crucial and, with proper understanding of the factors that influence the realization of beneficial impacts, estrogen-containing treatments may still be among these. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats: We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-βE2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions. ChAT activity was decreased in the hippocampus but not the frontal cortex of 5-week OVX animals. E2 replacement resulted in a reversal of this effect. At the 28-week time period, an unexpected decrease in ChAT activity was observed across all treatment groups. Interestingly, E2-pellet animals demonstrated the least severe decline in ChAT. This phenomenon was most evident in the frontal cortex where ChAT decreased by 61 and 56% in INTACT and OVX animals, respectively, whereas the decline in E2-pellet animals was only 16% over the same time period, suggesting a previously unreported cytoprotective effect of E2. Taken together, these findings demonstrate important effects of estrogens on cholinergic neurons and support the potential use of estrogen therapy in treatment of dementias in postmenopausal women. © 1994. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effect of selenium on methylmercury toxicity: a possible mechanism

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

Chang, L.W.; Suber, R.

1982-09-01

Young adult male Charles River rats were injected (i.p.) with 2.0 mg/kg b.w. methylmercury chloride (MeHg), with 2.0 mg/kg b.w. sodium selenite (Se), or with 2.0 mg/kg b.w. MeHg and 2.0 mg/kg b.w. Se. Erythrocytic glutathione peroxidase activity was determined and the rate of oxidation of NADPH with t-butyl-hydroperoxide as a substrate was followed at 340 nm and 25/sup 0/C. Toxic signs (crossing reflex of the hind limbs) were displayed by MeHg-treated animals by the 6th week of intoxication. By 8 weeks of the experiment, overt neurological signs (crossing reflex, ataxic gait, and weight loss) were observed in MeHg-treated animals.more » No observable toxic signs or symptoms were evident in the control animals (saline or Se-treated) and in the MeHg/Se treated rats. Results have confirmed that exposure to methyl-mercury suppresses the activity of glutathione peroxidase. Furthermore, it was demonstrated that with co-administration of selenium (sodium selenite), the inhibitory effect of MeHg on GSH-Px was totally alleviated. These findings suggest that the level of GSH-Px level is important in influencing the toxic consequences in MeHg-intoxicated animals and may be useful as a predictive indicator for methylmercury toxic conditions of the animals. (JMT)« less

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

PubMed

Vuola, J; Göransson, H; Böhling, T; Asko-Seljavaara, S

1996-09-01

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.

Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold.

PubMed

Zhou, X Z; Leung, V Y; Dong, Q R; Cheung, K M; Chan, D; Lu, W W

2008-06-01

This study investigates the capacity of a composite scaffold composed of polyglycolic acid-hydroxyapatite (PGA-HA) and autologous mesenchymal stem cells (MSCs) to promote repair of osteochondral defects. MSCs from culture-expanded rabbits were seeded onto a PGA and HA scaffold. After a 72-hour co-culture period, the cell-adhered PGA and HA were joined together, forming an MSCs-PGA-HA composite. Full-thickness cartilage defects in the intercondylar fossa of the femur were then implanted with the MSC-PGA-HA composite, the PGA-HA scaffold only, or they were left empty (n=20). Animals were sacrificed 16 or 32 weeks after surgery and the gross appearance of the defects was evaluated. The specimens were examined histologically for morphologic features, and stained immunohistochemically for type 2 collagen. Specimens of the MSCs-PGA-HA composite implantation group demonstrated hyaline cartilage and a complete subchondral bone formation. At 16 weeks post-implantation, significant integration of the newly formed tissue with surrounding normal cartilage and subchondral bone was observed when compared to the two control groups. At 32 weeks, no sign of progressive degeneration of the newly formed tissue was found. A significant difference in histological grading score was found compared with the control groups. The novel MSCs-seeded, PGA-HA biphasic graft facilitated both articular cartilage and subchondral bone regeneration in an animal model and might serve as a new approach for clinical applications.

Effects of Two Training Programs on Transcriptional Levels of Neurotrophins and Glial Cells Population in Hippocampus of Experimental Multiple Sclerosis.

PubMed

Naghibzadeh, Maryam; Ranjbar, Rouhollah; Tabandeh, Mohammad Reza; Habibi, Abdolhamid

2018-05-18

The aim of the present study was to investigate the effects of high-intensity interval training (HIIT) versus low-intensity continuous training (LICT) on transcriptional levels of neurotrophic factors and oligodendrocyte/microglia cell loss in a cuprizone (CP) induced animal model of demyelination. Male C57BL/6 mice were assigned to six groups: control (C), cuprizone-induced demyelination (CP), interval training (IT), continuous training (CT), IT plus CP (ITCP), and CT plus CP (CTCP). Training programs on the treadmill were performed for four weeks, and then demyelination was induced by feeding mice a diet containing 0.2% cuprizone for five weeks. Animals that received cuprizone showed poorer motor function, lower expression of BDNF, GDNF, NGF, and fewer oligodendrocytes in the hippocampus compared to the control animals. The numbers of oligodendrocyte and microglia cells increased in the ITCP group compared to the CTCP group (P<0.05). Both training programs increased the mRNA levels of BDNF, GDNF and NGF, and the HIIT program was more effective than the LICT program (P<0.05). Both exercise programs prevented the abnormal neurological movements induced by cuprizone. Our results indicated that HIIT versus LICT had a greater neuroprotective effect against multiple sclerosis by improving gene expression for abnormal neurotrophins and cellular loss in the hippocampus. © Georg Thieme Verlag KG Stuttgart · New York.

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

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.

The Association Between Effective Dose of Magnesium and Mild Compulsive Exercise on Spatial Learning, Memory, and Motor Activity of Adult Male Rats.

PubMed

Hajizade Ghonsulakandi, Shahnaz; Sheikh, Mahmuod; Dehghan Shasaltaneh, Marzieh; Chopani, Samira; Naghdi, Nasser

2017-08-01

One of the most important survival mechanisms is learning and memory processes. To emphasize the role of physical exercises and magnesium (Mg) in improvement of cognitive performance, we planned to investigate the effect of Mg and mild compulsive exercise on spatial learning and memory of adult male rats. Accordingly, we divided male Wistar rats into four groups: (I) control, (II) Mg treatment, (III) exercise, and (IV) Mg-exercise in the different dosages of Mg (0.5, 1, 1.5, and 2 mmol/kbw) were injected in the form of gavage during 1 week. Also, 1-week mild running on treadmill was used for exercise treatment. The Morris water maze (MWM) test and open field tool were used to evaluate spatial learning, memory, and motor activity, respectively. Our results clearly showed that 1 mmol/kbw Mg was applied as an effective dosage. Strikingly, 1-week mild exercise on treadmill had no significant effect on spatial motor activity, learning, and memory. Feeding 1 mmol/kbw Mg for a week showed a significant difference in learning and exploration stages. Compared to control animals, these results reveal exercise and Mg simultaneously had effect on learning and reminding. As a consequence, although mild exercise had no effect on motor activity and memory, Mg intake improved spatial learning, memory, and locomotor activity. The Mg feeding could be a promising supplemental treatment in the neurodegenerative disease. It is worthwhile to mention consumption of Mg leads to enhancement of memory, so animals find the hidden platform with the highest velocity.

Adolescent Traumatic Brain Injury Induces Chronic Mesolimbic Neuroinflammation with Concurrent Enhancement in the Rewarding Effects of Cocaine in Mice during Adulthood.

PubMed

Merkel, Steven F; Razmpour, Roshanak; Lutton, Evan M; Tallarida, Christopher S; Heldt, Nathan A; Cannella, Lee Anne; Persidsky, Yuri; Rawls, Scott M; Ramirez, Servio H

2017-01-01

Clinical psychiatric disorders of depression, anxiety, and substance abuse are most prevalent after traumatic brain injury (TBI). Pre-clinical research has focused on depression and anxiety post-injury; however, virtually no data exist examining whether the preference for illicit drugs is affected by traumatic injury in the developing adolescent brain. Using the controlled cortical impact (CCI) model of TBI and the conditioned place preference (CPP) assay, we tested the underlying hypothesis that brain injury during adolescence exacerbates the rewarding properties of cocaine in adulthood possibly through an active inflammatory status in the mesolimbic pathway. Six-week old, C57BL/6 mice sustained a single CCI-TBI to the right somatosensory cortex. CPP experiments with cocaine began 2 weeks post-TBI. Animals receiving cocaine displayed significant place preference shifts compared to saline controls. Further, within the cocaine-experienced cohort, moderate CCI-TBI during adolescence significantly increased the preference shift in adulthood when compared to naïve controls. Additionally, persistent neuroinflammatory responses were observed in the cortex, nucleus accumbens (NAc), and ventral tegmental area post-CCI-TBI. Significant increases in both astrocytic, glial fibrillary acidic protein, and microglial, ionization basic acid 1, markers were observed in the NAc at the end of CPP testing. Moreover, analysis using focused array gene expression panels identified the upregulation of numerous inflammatory genes in moderate CCI-TBI animals, compared to naïve controls, both in the cortex and NAc at 2 weeks post-TBI, before onset of cocaine administration. These results suggest that sustaining moderate TBI during adolescence may augment the rewarding effects of psychostimulants in adulthood, possibly by induction of chronic mesolimbic neuroinflammation.

Physiological and biochemical changes after boldenone injection in adult rabbits.

PubMed

Tousson, Ehab; El-Moghazy, Mostafa; Massoud, Ahmed; El-Atrash, Afaf; Sweef, Osama; Akel, Amani

2016-01-01

Boldenone (BOL) is an androgenic steroid that improves the growth and food conversion in food-producing animals. In most countries worldwide, this anabolic steroid is forbidden for human uses and meat production as it was developed for veterinary use. Recently, BOL is used by bodybuilders in both off season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the physiological and biochemical changes in rabbits after injection with the growth promoter BOL. A total of 32 adult New Zealand rabbits were divided into four groups, where the control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. The remaining three experimental groups included animals that received one, two and three intramuscular injections of 5 mg/kg body weight BOL, respectively, and were dissected after 3, 6 and 9 weeks, respectively. The animals from practice appeared healthy and did not show clinical signs of disease and none of the rabbits died during the experimental period. Serum total protein, globulin, alanine aminotransferase, asparate aminotransferase, urea, creatinine, testosterone, luteinizing hormone and follicle-stimulating hormone levels were significantly increased while serum direct bilirubin, albumin and albumin/globulin ratio were significantly decreased (p < 0.05) after one, two and three intramuscular injections of BOL as compared to their relative values in the control group. These findings explain the common phenomena in athletes and bodybuilders who suffer from infertility, renal and hepatic alterations following injection with some drugs as steroids (BOL) to build muscles. © The Author(s) 2013.

Prosthesis Control with an Implantable Multichannel Wireless Electromyography System for High-Level Amputees: A Large-Animal Study.

PubMed

Bergmeister, Konstantin D; Hader, Marie; Lewis, Soeren; Russold, Michael-Friedrich; Schiestl, Martina; Manzano-Szalai, Krisztina; Roche, Aidan D; Salminger, Stefan; Dietl, Hans; Aszmann, Oskar C

2016-01-01

Myoelectric prostheses lack a strong human-machine interface, leading to high abandonment rates in upper limb amputees. Implantable wireless electromyography systems improve control by recording signals directly from muscle, compared with surface electromyography. These devices do not exist for high amputation levels. In this article, the authors present an implantable wireless electromyography system for these scenarios tested in Merino sheep for 4 months. In a pilot trial, the electrodes were implanted in the hind limbs of 24 Sprague-Dawley rats. After 8 or 12 weeks, impedance and histocompatibility were assessed. In the main trial, the system was tested in four Merino sheep for 4 months. Impedance of the electrodes was analyzed in two animals. Electromyographic data were analyzed in two freely moving animals repeatedly during forward and backward gait. Device implantation was successful in all 28 animals. Histologic evaluation showed a tight encapsulation after 8 weeks of 78.2 ± 26.5 µm subcutaneously and 92.9 ± 31.3 µm on the muscular side. Electromyographic recordings show a distinct activation pattern of the triceps, brachialis, and latissimus dorsi muscles, with a low signal-to-noise ratio, representing specific patterns of agonist and antagonist activation. Average electrode impedance decreased over the whole frequency range, indicating an improved electrode-tissue interface during the implantation. All measurements taken over the 4 months of observation used identical settings and showed similar recordings despite changing environmental factors. This study shows the implantation of this electromyography device as a promising alternative to surface electromyography, providing a potentially powerful wireless interface for high-level amputees.

Pronation-Supination Motion Is Altered in a Rat Model of Post-Traumatic Elbow Contracture.

PubMed

Dunham, Chelsey L; Castile, Ryan M; Chamberlain, Aaron M; Galatz, Leesa M; Lake, Spencer P

2017-07-01

The elbow joint is highly susceptible to joint contracture, and treating elbow contracture is a challenging clinical problem. Previously, we established an animal model to study elbow contracture that exhibited features similar to the human condition including persistent decreased range of motion (ROM) in flexion-extension and increased capsule thickness/adhesions. The objective of this study was to mechanically quantify pronation-supination in different injury models to determine if significant differences compared to control or contralateral persist long-term in our animal elbow contracture model. After surgically inducing soft tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II (anterior capsulotomy with lateral collateral ligament transection), limbs were immobilized for 6 weeks (immobilization (IM)). Animals were evaluated after the IM period or following an additional 6 weeks of free mobilization (FM). Total ROM for pronation-supination was significantly decreased compared to the uninjured contralateral limb for both IM and FM, although not different from control limbs. Specifically, for both IM and FM, total ROM for Injury I and Injury II was significantly decreased by ∼20% compared to contralateral. Correlations of measurements from flexion-extension and pronation-supination divulged that FM did not affect these motions in the same way, demonstrating that joint motions need to be studied/treated separately. Overall, injured limbs exhibited persistent motion loss in pronation-supination when comparing side-to-side differences, similar to human post-traumatic joint contracture. Future work will use this animal model to study how elbow periarticular soft tissues contribute to contracture.

Thermal acclimation and nutritional history affect the oxidation of different classes of exogenous nutrients in Siberian hamsters, Phodopus sungorus.

PubMed

McCue, Marshall D; Voigt, Christian C; Jefimow, Małgorzata; Wojciechowski, Michał S

2014-11-01

During acclimatization to winter, changes in morphology and physiology combined with changes in diet may affect how animals use the nutrients they ingest. To study (a) how thermal acclimation and (b) nutritional history affect the rates at which Siberian hamsters (Phodopus sungorus) oxidize different classes of dietary nutrients, we conducted two trials in which we fed hamsters one of three (13) C-labeled compounds, that is, glucose, leucine, or palmitic acid. We predicted that under acute cold stress (3 hr at 2°C) hamsters previously acclimated to cold temperatures (10°C) for 3 weeks would have higher resting metabolic rate (RMR) and would oxidize a greater proportion of dietary fatty acids than animals acclimated to 21°C. We also investigated how chronic nutritional stress affects how hamsters use dietary nutrients. To examine this, hamsters were fed four different diets (control, low protein, low lipid, and low-glycemic index) for 2 weeks. During cold challenges, hamsters previously acclimated to cold exhibited higher thermal conductance and RMR, and also oxidized more exogenous palmitic acid during the postprandial phase than animals acclimated to 21°C. In the nutritional stress trial, hamsters fed the low protein diet oxidized more exogenous glucose, but not more exogenous palmitic acid than the control group. The use of (13) C-labeled metabolic tracers combined with breath testing demonstrated that both thermal and nutritional history results in significant changes in the extent to which animals oxidize dietary nutrients during the postprandial period. © 2014 Wiley Periodicals, Inc.

Effects of a post-weaning cafeteria diet in young rats: metabolic syndrome, reduced activity and low anxiety-like behaviour.

PubMed

Lalanza, Jaume F; Caimari, Antoni; del Bas, Josep M; Torregrosa, Daniel; Cigarroa, Igor; Pallàs, Mercè; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M

2014-01-01

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.

Effects Of A Post-Weaning Cafeteria Diet In Young Rats: Metabolic Syndrome, Reduced Activity And Low Anxiety-Like Behaviour

PubMed Central

Lalanza, Jaume F.; Caimari, Antoni; del Bas, Josep M.; Torregrosa, Daniel; Cigarroa, Igor; Pallàs, Mercè; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M.

2014-01-01

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight. PMID:24482678

Disruption of Locomotion in Response to Hindlimb Muscle Stretch at Acute and Chronic Time Points after a Spinal Cord Injury in Rats.

PubMed

Keller, Anastasia V P; Wainwright, Grace; Shum-Siu, Alice; Prince, Daniella; Hoeper, Alyssa; Martin, Emily; Magnuson, David S K

2017-02-01

After spinal cord injury (SCI) muscle contractures develop in the plegic limbs of many patients. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCI. The purpose of the current study was to determine the effects of stretching on locomotor function at acute and chronic time points after moderately severe contusive SCI. Female Sprague-Dawley rats with 25 g-cm T10 contusion injuries received our standard 24-min stretching protocol starting 4 days (acutely) or 10 weeks (chronically) post-injury (5 days/week for 5 or 4 weeks, respectively). Locomotor function was assessed using the BBB (Basso, Beattie, and Bresnahan) Open Field Locomotor Scale, video-based kinematics, and gait analysis. Locomotor deficits were evident in the acute animals after only 5 days of stretching and increasing the perceived intensity of stretching at week 4 resulted in greater impairment. Stretching initiated chronically resulted in dramatic decrements in locomotor function because most animals had BBB scores of 0-3 for weeks 2, 3, and 4 of stretching. Locomotor function recovered to control levels for both groups within 2 weeks once daily stretching ceased. Histological analysis revealed no apparent signs of overt and persistent damage to muscles undergoing stretching. The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.

Brief electrical stimulation after facial nerve transection and neurorrhaphy: a randomized prospective animal study.

PubMed

Mendez, Adrian; Seikaly, Hadi; Biron, Vincent L; Zhu, Lin Fu; Côté, David W J

2016-02-01

Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurement in these studies has not been precise or accurate. The objective of this study is to assess the effect of BES on accelerating facial nerve functional recovery from a transection injury in the rat model. A prospective randomized animal study using a rat model was performed. Two groups of 9 rats underwent facial nerve surgery. Both group 1 and 2 underwent facial nerve transection and repair at the main trunk of the nerve, with group 2 additionally receiving BES on post-operative day 0 for 1 h using an implantable stimulation device. Primary outcome was measured using a laser curtain model, which measured amplitude of whisking at 2, 4, and 6 weeks post-operatively. At week 2, the average amplitude observed for group 1 was 4.4°. Showing a statistically significant improvement over group 1, the group 2 mean was 14.0° at 2 weeks post-operatively (p = 0.0004). At week 4, group 1 showed improvement having an average of 9.7°, while group 2 remained relatively unchanged with an average of 12.8°. Group 1 had an average amplitude of 13.63° at 6-weeks from surgery. Group 2 had a similar increase in amplitude with an average of 15.8°. There was no statistically significant difference between the two groups at 4 and 6 weeks after facial nerve surgery. This is the first study to use an implantable stimulator for serial BES following neurorrhaphy in a validated animal model. Results suggest performing BES after facial nerve transection and neurorrhaphy at the main trunk of the facial nerve is associated with accelerated whisker movement in a rat model compared with a control group.

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

PubMed

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

2007-07-01

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

Interleukin-2-dependent mechanisms are involved in the development of glomerulosclerosis after partial renal ablation in rats.

PubMed

Hamar, P; Peti-Peterdi, J; Szabó, A; Becker, G; Flach, R; Rosivall, L; Heemann, U

2001-01-01

Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-beta (TGF-beta(1)), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney. Copyright 2001 S. Karger AG, Basel

Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations.

PubMed

Belkacemi, Louiza; Selselet-Attou, Ghalem; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

2010-11-01

This study deals with the effects of daily intermittent fasting for 15 h upon the development of diabetes in sand rats exposed to a hypercaloric diet. The same pattern of daily intermittent fasting was imposed on sand rats maintained on a purely vegetal diet (control animals). Over the last 30 days of the present experiments, non-fasting animals gained weight, whilst intermittently fasting sand rats lost weight. In this respect, there was no significant difference between control animals and either diabetic or non-diabetic sand rats exposed to the hypercaloric diet. The postprandial glycemia remained fairly stable in the control animals. During a 3-week transition period from a purely vegetal to a hypercaloric diet, the post-prandial glycemia increased by 5.95 ± 1.26 mM (n=6) in diabetic sand rats, as distinct from an increase of only 0.45 ± 0.56 mM (n=6) in the non-diabetic animals. During the intermittent fasting period, the postprandial glycemia decreased significantly in the diabetic animals, but not so in the non-diabetic sand rats. Before the switch in food intake, the peak glycemia at the 30th min of an intraperitoneal glucose tolerance test was already higher in the diabetic than non-diabetic rats. In both the non-diabetic and diabetic sand rats, intermittent fasting prevented the progressive deterioration of glucose tolerance otherwise observed in non-fasting animals. These findings reveal that, at least in sand rats, intermittent daily fasting prevents the progressive deterioration of glucose tolerance otherwise taking place when these animals are exposed to a hypercaloric diet.

[Effectiveness of dog-assisted therapy in the elderly. A preliminary study].

PubMed

Folch, Anabel; Torrente, Margarita; Heredia, Luis; Vicens, Paloma

2016-01-01

Animal-assisted therapy is increasingly present in several educational and health areas. The aim of this study is to assess the effectiveness of such interventions in the elderly population living in residential settings. A 12-week dog-assisted intervention program was designed, with 16 participants from a nursing home divided into an experimental group and a control group. Several physical and psychological variables were assessed before and after the intervention. While there were no significant differences in the control group, the experimental group improved significantly after participating in the program. The results support the hypothesis that animal-assisted interventions may be beneficial for residents in elderly care homes. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Chronic diabetes increases advanced glycation end products on cardiac ryanodine receptors/calcium-release channels.

PubMed

Bidasee, Keshore R; Nallani, Karuna; Yu, Yongqi; Cocklin, Ross R; Zhang, Yinong; Wang, Mu; Dincer, U Deniz; Besch, Henry R

2003-07-01

Decrease in cardiac contractility is a hallmark of chronic diabetes. Previously we showed that this defect results, at least in part, from a dysfunction of the type 2 ryanodine receptor calcium-release channel (RyR2). The mechanism(s) underlying RyR2 dysfunction is not fully understood. The present study was designed to determine whether non-cross-linking advanced glycation end products (AGEs) on RyR2 increase with chronic diabetes and if formation of these post-translational complexes could be attenuated with insulin treatment. Overnight digestion of RyR2 from 8-week control animals (8C) with trypsin afforded 298 peptides with monoisotopic mass (M+H(+)) >or=500. Digestion of RyR2 from 8-week streptozotocin-induced diabetic animals (8D) afforded 21% fewer peptides, whereas RyR2 from 6-week diabetic/2-week insulin-treated animals generated 304 peptides. Using an in-house PERLscript algorithm, search of matrix-assisted laser desorption ionization-time of flight mass data files identified several M+H(+) peaks corresponding to theoretical RyR2 peptides with single N(epsilon)-(carboxymethyl)-lysine, imidazolone A, imidazone B, pyrraline, or 1-alkyl-2-formyl-3,4-glycosyl pyrrole modification that were present in 8D but not 8C. Insulin treatment minimized production of some of these nonenzymatic glycation products. These data show for the first time that AGEs are formed on intracellular RyR2 during diabetes. Because AGE complexes are known to compromise protein activity, these data suggest a potential mechanism for diabetes-induced RyR2 dysfunction.

Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.

Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

PubMed

McCall, M A; Tieman, D G; Hirsch, H V

1982-11-04

In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

Science Education in Primary Schools: Is an Animation Worth a Thousand Pictures?

NASA Astrophysics Data System (ADS)

Barak, Miri; Dori, Yehudit J.

2011-10-01

Science teaching deals with abstract concepts and processes that very often cannot be seen or touched. The development of Java, Flash, and other web-based applications allow teachers and educators to present complex animations that attractively illustrate scientific phenomena. Our study evaluated the integration of web-based animated movies into primary schools science curriculum. Our goal was to examine teachers' methods for integrating animated movies and their views about the role of animations in enhancing young students' thinking skills. We also aimed at investigating the effect of animated movies on students' learning outcomes. Applying qualitative and quantitative tools, we conducted informal discussions with science teachers (N = 15) and administered pre- and post-questionnaires to 4th (N = 641) and 5th (N = 694) grade students who were divided into control and experimental groups. The experimental group students studied science while using animated movies and supplementary activities at least once a week. The control group students used only textbooks and still-pictures for learning science. Findings indicated that animated movies support the use of diverse teaching strategies and learning methods, and can promote various thinking skills among students. Findings also indicated that animations can enhance scientific curiosity, the acquisition of scientific language, and fostering scientific thinking. These encouraging results can be explained by the fact that the students made use of both visual-pictorial and auditory-verbal capabilities while exploring animated movies in diverse learning styles and teaching strategies.

Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

PubMed

Heemann, U W; Azuma, H; Tullius, S G; Schmid, C; Philipp, T; Tilney, N L

1996-07-01

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that developing in non-treated rats at 24 weeks. Activation of graft endothelium and/or host leucocytes increased the pace of graft infiltration and the expression of cytokines and other molecules. These events accelerate the process of chronic rejection.

N-Acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure

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

Pinho, R.A.; Silveira, P.C.L.; Silva, L.A.

2005-11-01

Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8),more » and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n = 8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust.« less

40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the mating period and, approximately, two weeks post-mating). In view of the limited pre-mating dosing...) Selection of animal species. This test standard is designed for use with the rat. If other species are used... three test groups and a control group should be used. Dose levels may be based on information from acute...

40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the mating period and, approximately, two weeks post-mating). In view of the limited pre-mating dosing...) Selection of animal species. This test standard is designed for use with the rat. If other species are used... three test groups and a control group should be used. Dose levels may be based on information from acute...

40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the mating period and, approximately, two weeks post-mating). In view of the limited pre-mating dosing...) Selection of animal species. This test standard is designed for use with the rat. If other species are used... three test groups and a control group should be used. Dose levels may be based on information from acute...

High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.

PubMed

Ranganathan, Kavitha; Hong, Xiaowei; Cholok, David; Habbouche, Joe; Priest, Caitlin; Breuler, Christopher; Chung, Michael; Li, John; Kaura, Arminder; Hsieh, Hsiao Hsin Sung; Butts, Jonathan; Ucer, Serra; Schwartz, Ean; Buchman, Steven R; Stegemann, Jan P; Deng, Cheri X; Levi, Benjamin

2018-04-01

Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n=5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. Using SUSI, HO was visualized as early as 1week after injury. HO was visualized earliest by 4weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n=5). Spectroscopic foci of HO present at 1week that persisted throughout all time points correlated with the HO present at 9weeks on micro CT imaging. SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO. Copyright © 2018 Elsevier Inc. All rights reserved.

The efficacy of deferiprone on tissues aluminum removal and copper, zinc, manganese level in rabbits.

PubMed

Liu, Ping; Yao, Yu-Na; Wu, Shi-De; Dong, Huai-Jun; Feng, Guo-Chang; Yuan, Xiao-Yan

2005-08-01

The effect of 1,2-dimethyl-3-hydroxypyrid-4-one [deferiprone (DE)] on aluminum mobilization and elimination from tissues and serum as well as the influence on the excretion of trace elements, copper, zinc and manganese in rabbits was investigated. Sixteen New Zealand rabbits were randomly divided into three groups: control, Al-only and Al+DE. The Al-only and Al+DE animals received injections of Al2(SO43.18H2O 600 micromol Al/kg 5 days per week for 3 weeks. One week after the last Al injection the Al+DE rabbits were given deferiprone 750 micromol/kg/day intragastrically for 2 weeks. At the 42nd day the animals were sacrificed and the organs were taken and digested. Blood was taken from the ear artery three times (at the initiation of the experiment, before and after deferiprone administration). The aluminum and copper, zinc, manganese were determined by atomic absorption spectrophotometry. Our results showed that deferiprone could highly mobilize aluminum stores from tissues. At the end of experiment the aluminum contents of bone, kidney, liver and brain in Al+DE were significantly lower than that in Al-only rabbits. The copper, zinc, manganese contents were not affected by deferiprone administration.

Chemoprevention of oral cancer by lyophilized strawberries.

PubMed

Casto, Bruce C; Knobloch, Thomas J; Galioto, Rebecca L; Yu, Zhangsheng; Accurso, Brent T; Warner, Blake M

2013-11-01

Oral cancer represents approximately 2.5% of all cancers in the United States, with five- and 10-year survival rates of 62% and 51%. In the present study, lyophilized strawberries (LS) were evaluated for their potential to inhibit tumorigenesis in the hamster cheek pouch (HCP) model of oral cancer and for their ability to modify expression of several genes relevant to oral cancer development. HCPs were painted three times a week for six weeks with 0.2% 7,12-dimethylbenz(a)anthracene (DMBA). Hamsters were given 5% or 10% LS in their diet prior to, during, and after, or only after carcinogen treatment. Animals were sacrificed 12 weeks from the beginning of DMBA treatment and the number of total lesions and tumors was determined. A significant difference (p<0.01-0.04) in the number of tumors was found between the LS-treated groups and the carcinogen controls. Histological examination of HCPs revealed a significant reduction in mild and severe dysplasia following 12 weeks of treatment with LS. Molecular analysis revealed that genes related to tumor development were modulated by LS. These experiments support previous studies in HCP that demonstrated a chemopreventive activity by black raspberries and show, to our knowledge for the first time, that strawberries can inhibit tumor formation in an animal model of oral cancer.

[Karyometry of BBN-induced precancerosis of the urothelium : An experimental analysis].

PubMed

Dahm, H H; Lehnen-Holtum, V; Rübben, H

2016-10-01

The morphology of experimental precancerous lesions of the urinary bladder has been interpreted quite differently by various authors. The aim of this investigation was to quantify these lesions by karyometry and, thus, to gain a more reliable understanding of the process. A total of 60 Wistar rats were fed with N‑butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a concentration of 0.05 % in their drinking water to induce preneoplastic changes of the urothelium. After the second week of BBN exposition, 6 animals were killed every 2 weeks up to week 20. Smears of the scraped off urothelium of 3 urinary bladders of each group were analyzed cytologically and karyometrically. BBN exposition led to statistically significant changes of the karyometric values using the χ 2 test to differentiate the control animals from the ones that had ingested BBN and the 2‑week groups from each other. These changes consisted mainly in significant deviations of the size of the nuclear area within the different groups. Morphological and karyometrical analysis showed that biologically relevant stages in the development of chemically induced urothelial precancerous lesions could be realized much earlier than had been assumed in recent publications. Karyometric analysis offered a valid basis to describe the early morphologic alterations of carcinogenesis.

Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in a model of type 2 diabetes

PubMed Central

Nam, Sung Min; Kim, Jong Whi; Yoo, Dae Young; Jung, Hyo Young; Choi, Jung Hoon; Hwang, In Koo; Seong, Je Kyung

2016-01-01

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals. PMID:27051335

In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.

PubMed

Hansen, Jennifer K; Thibeault, Susan L; Walsh, Jennifer F; Shu, Xiao Zheng; Prestwich, Glenn D

2005-09-01

A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.

The benefits of endurance training in cardiomyocyte function in hypertensive rats are reversed within four weeks of detraining.

PubMed

Carneiro-Júnior, Miguel Araujo; Quintão-Júnior, Judson Fonseca; Drummond, Lucas Rios; Lavorato, Victor Neiva; Drummond, Filipe Rios; da Cunha, Daise Nunes Queiroz; Amadeu, Marco Aurélio; Felix, Leonardo Bonato; de Oliveira, Edilamar Menezes; Cruz, Jader Santos; Prímola-Gomes, Thales Nicolau; Mill, José Geraldo; Natali, Antonio José

2013-04-01

The aim of the present study was to verify the effects of low-intensity endurance training and detraining on the mechanical and molecular properties of cardiomyocytes from spontaneously hypertensive rats (SHRs). Male SHRs and normotensive control Wistar rats at 16-weeks of age were randomly divided into eight groups of eight animals: NC8 and HC8 (normotensive and hypertensive control for 8weeks); NT8 and HT8 (normotensive and hypertensive trained at 50-60% of maximal exercise capacity for 8weeks); NC12 and HC12 (normotensive and hypertensive control for 12weeks); NDT and HDT (normotensive and hypertensive trained for 8weeks and detrained for 4weeks). The total exercise time until fatigue (TTF) was determined by a maximal exercise capacity test. Resting heart rate (RHR) and systolic arterial pressure (SAP) were measured. After the treatments, animals were killed by cervical dislocation and left ventricular myocytes were isolated by enzymatic dispersion. Isolated cells were used to determine intracellular global Ca(2+) ([Ca(2+)]i) transient and cardiomyocyte contractility (1Hz; ~25°C). [Ca(2+)]i regulatory proteins were measured by Western blot, and the markers of pathologic cardiac hypertrophy by quantitative real-time polymerase chain reaction (q-RT-PCR). Exercise training augmented the TTF (NC8, 11.4±1.5min vs. NT8, 22.5±1.4min; HC8, 11.7±1.4min vs. HT8, 24.5±1.3min; P<0.05), reduced RHR (NT8initial, 340±8bpm vs. NT8final, 322±10bpm; HT8initial, 369±8bpm vs. HT8final, 344±10bpm; P<0.05), and SBP in SHR animals (HC8, 178±3mmHg vs. HT8, 161±4mmHg; P<0.05). HC8 rats showed a slower [Ca(2+)]i transient (Tpeak, 83.7±1.8ms vs. 71.7±2.4ms; T50%decay, 284.0±4.3ms vs. 264.0±4.1ms; P<0.05) and cell contractility (Vshortening, 86.1±6.7μm/s vs. 118.6±6.7μm/s; Vrelengthening, 57.5±7.4μm/s vs. 101.3±7.4μm/s; P<0.05), and higher expression of ANF (300%; P<0.05), skeletal α-actin (250%; P<0.05) and a decreased α/β-MHC ratio (70%; P<0.05) compared to NC8. Exercise training increased [Ca(2+)]i transient (NC8, 2.39±0.06F/F0 vs. NT8, 2.72±0.06F/F0; HC8, 2.28±0.05F/F0 vs. HT8, 2.82±0.05F/F0; P<0.05), and cell contractility (NC8, 7.4±0.3% vs. NT8, 8.4±0.3%; HC8, 6.8±0.3% vs. HT8, 7.8±0.3%; P<0.05). Furthermore, exercise normalized the expression of ANF, skeletal α-actin, and the α/β-MHC ratio in HT8 rats, augmented the expression of SERCA2a (NC8, 0.93±0.15 vs. NT8, 1.49±0.14; HC8, 0.83±0.13 vs. HT8, 1.32±0.14; P<0.05) and PLBser16 (NC8, 0.89±0.18 vs. NT8, 1.23±0.17; HC8, 0.77±0.17 vs. HT8, 1.32±0.16; P<0.05), and reduced PLBt/SERCA2a (NC8, 1.21±0.19 vs. NT8, 0.50±0.21; HC8, 1.38±0.17 vs. HT8, 0.66±0.21; P<0.05). However, all these adaptations returned to control values within 4weeks of detraining in both SHR and normotensive control animals. In conclusion, low-intensity endurance training induces positive benefits to left ventricular myocyte mechanical and molecular properties, which are reversed within 4weeks of detraining. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantifying subtle but persistent peri-spine inflammation in vivo to submicron cobalt-chromium alloy particles.

PubMed

Hallab, Nadim James; Chan, Frank W; Harper, Megan L

2012-12-01

We evaluated the consequences of cobalt-chromium alloy (CoCr) wear debris challenge in the peri-spine region to determine the inflammation and toxicity associated with submicron particulates of CoCr-alloy and nickel on the peri-spine. The lumbar epidural spaces of (n = 50) New Zealand white rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy and Ni particles had a mean diameter of 0.2 and 0.6 μm, respectively. Five rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues were analyzed histologically and quantitatively analyzed immunohistochemically (TNF-α and IL-6). Histologically, wear particles were observed in all animals. There was no evidence of toxicity or local irritation noted during macroscopic observations in any CoCr-dosed animals. However, Ni-treated control animals experienced bilateral hind leg paralysis and were euthanized at Day 2. Histopathology of the Ni particle-treated group revealed severe neuropathy. Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent increase in cytokines (IL-6, TNF-α, p < 0.05) at 12 and 24 weeks. Subtle peri-spine inflammation associated with CoCr-alloy implant particles was dose dependent and persistent. Neuropathy can be induced by highly reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant debris (e.g., TDA) is consistent with past reports using titanium alloy particles, i.e., mild persistent inflammation.

Design and validation of a novel learning tool, the "Anato-Rug," for teaching equine topographical anatomy.

PubMed

Braid, Francesca; Williams, Sarah B; Weller, Renate

2012-01-01

Recognition of anatomical landmarks in live animals (and humans) is key for clinical practice, but students often find it difficult to translate knowledge from dissection-based anatomy onto the live animal and struggle to acquire this vital skill. The purpose of this study was to create and evaluate the use of an equine anatomy rug ("Anato-Rug") depicting topographical anatomy and key areas of lung, heart, and gastrointestinal auscultation, which could be used together with a live horse to aid learning of "live animal" anatomy. Over the course of 2 weeks, 38 third year veterinary students were randomly allocated into an experimental group, revising topographical anatomy from the "Anato-Rug," or a control group, learning topographical anatomy from a textbook. Immediately post activity, both groups underwent a test on live anatomy knowledge and were retested 1 week later. Both groups then completed a questionnaire to ascertain their perceptions of their learning experiences. Results showed that the experimental groups scored significantly higher than the control group at the first testing session, experienced more enjoyment during the activity and gained more confidence in identifying anatomical landmarks than the control group. There was not a significant difference in scores between groups at the second testing session. The findings indicate that the anatomy rug is an effective learning tool that aids understanding, confidence, and enjoyment in learning equine thorax and abdominal anatomy; however it was not better than traditional methods with regards to longer term memory recall. Copyright © 2012 American Association of Anatomists.

Exposure to mobile phone electromagnetic field radiation, ringtone and vibration affects anxiety-like behaviour and oxidative stress biomarkers in albino wistar rats.

PubMed

Shehu, Abubakar; Mohammed, Aliyu; Magaji, Rabiu Abdussalam; Muhammad, Mustapha Shehu

2016-04-01

Research on the effects of Mobile phone radio frequency emissions on biological systems has been focused on noise and vibrations as auditory stressors. This study investigated the potential effects of exposure to mobile phone electromagnetic field radiation, ringtone and vibration on anxiety-like behaviour and oxidative stress biomarkers in albino wistar rats. Twenty five male wistar rats were randomly divided into five groups of 5 animals each: group I: exposed to mobile phone in switched off mode (control), group II: exposed to mobile phone in silent mode, group III: exposed to mobile phone in vibration mode, group IV: exposed to mobile phone in ringtone mode, group V: exposed to mobile phone in vibration and ringtone mode. The animals in group II to V were exposed to 10 min call (30 missed calls for 20 s each) per day for 4 weeks. Neurobehavioural studies for assessing anxiety were carried out 24 h after the last exposure and the animals were sacrificed. Brain samples were collected for biochemical evaluation immediately. Results obtained showed a significant decrease (P < 0.05) in open arm duration in all the experimental groups when compared to the control. A significant decrease (P < 0.05) was also observed in catalase activity in group IV and V when compared to the control. In conclusion, the results of the present study indicates that 4 weeks exposure to electromagnetic radiation, vibration, ringtone or both produced a significant effect on anxiety-like behavior and oxidative stress in young wistar rats.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model.

PubMed

Chen, C C; Chang, M W; Chang, C P; Chan, S C; Chang, W Y; Yang, C L; Lin, M T

2014-10-01

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Cerebrovasculoprotective effects of azilsartan medoxomil in diabetes.

PubMed

Abdelsaid, Mohammed; Coucha, Maha; Ergul, Adviye

2014-11-01

We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by the age of 18 weeks, which is characterized by increased media thickness and matrix deposition. Although early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II type 1 receptor blockers reverse pathologic vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new angiotensin II type 1 receptor blocker, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. Control Wistar and diabetic GK rats (n = 6-8 per group) were treated with vehicle (water) or azilsartan medoxomil (3 mg/kg/d) from the age of 14 to 18 or 18 to 22 weeks before or after vascular remodeling is established, respectively. Blood glucose and blood pressure were monitored and middle cerebral artery structure and function were evaluated using pressurized arteriography. Blood glucose was higher in GK rats compared with Wistar rats. Azilsartan treatment lowered blood glucose in diabetic animals with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross-sectional area compared with control group animals, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure. Published by Elsevier Inc.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

PubMed Central

Chen, C.C.; Chang, M.W.; Chang, C.P.; Chan, S.C.; Chang, W.Y.; Yang, C.L.; Lin, M.T.

2014-01-01

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use. PMID:25140816

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Viguiliouk, Effie; Stewart, Sarah E.; Jayalath, Viranda H.; Ng, Alena Praneet; Mirrahimi, Arash; de Souza, Russell J.; Hanley, Anthony J.; Bazinet, Richard P.; Blanco Mejia, Sonia; Leiter, Lawrence A.; Josse, Robert G.; Kendall, Cyril W.C.; Jenkins, David J.A.; Sievenpiper, John L.

2015-01-01

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%), FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L) and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321. PMID:26633472

Effects of Olanzapine, Risperidone and Haloperidol on Prepulse Inhibition in Schizophrenia Patients: A Double-Blind, Randomized Controlled Trial

PubMed Central

Wynn, Jonathan K.; Green, Michael F.; Sprock, Joyce; Light, Gregory A.; Widmark, Clifford; Reist, Christopher; Erhart, Stephen; Marder, Stephen R.; Mintz, Jim; Braff, David L.

2009-01-01

Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can “normalize” PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications. PMID:17662577

Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan.

PubMed Central

Kurokawa, Y; Takayama, S; Konishi, Y; Hiasa, Y; Asahina, S; Takahashi, M; Maekawa, A; Hayashi, Y

1986-01-01

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis. Images FIGURE 3. FIGURE 4. PMID:3816726

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

PubMed Central

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

2009-01-01

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

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.

Neurotoxicity of misonidazole in rats following intravenous administration.

PubMed

Graziano, M J; Henck, J W; Meierhenry, E F; Gough, A W

1996-06-01

Misonidazole is a hypoxic cell radiosensitizer that induces a peripheral neuropathy in humans after exceeding a schedule-dependent cumulative threshold dose. Clinical studies of misonidazole have been conducted using oral administration, whereas most other radiosensitizers have been administered intravenously. Since route of exposure can potentially influence the toxicity of xenobiotics, the objective of this study was to assess the neurotoxicity of misonidazole in rats following intravenous dosing using a battery of routine clinical, neurofunctional, biochemical, and histopathologic screening methods. Male Sprague-Dawley rats were administered intravenous doses of misonidazole at 0 (vehicle control), 100, 200, 300, or 400 mg kg-1 once per day, 5 days per week, for 2 weeks. Animals were evaluated for neurofunctional and pathological changes following termination of treatment (Days 15-17) and at the end of a 4 week observation period (Days 43-45). During the dosing phase, hypoactivity, salivation, rhinorrhea, chromodacryorrhea, rough pelage and ataxia were observed at 400 mg kg-1, and body weight gain of the 300 and 400 mg kg-1 groups was significantly decreased relative to the vehicle controls by 24% and 49%, respectively. Corresponding reductions in food consumption were 8% and 23%, respectively. Although most 400 mg kg-1 animals appeared normal on Day 15 prior to the neurofunctional evaluations, rotorod testing precipitated a number of clinical signs including: ataxia, impaired righting reflex, excessive rearing, tremors, vocalization, circling, head jerking, excessive sniffing and hyperactivity. All of these animals recovered and appeared normal from Day 17 through study termination. There were no treatment-related effects on motor activity, acoustic startle response, rotorod performance, forelimb group strength, toe and tail pinch reflexes, tibial nerve beta-glucuronidase activity or tail nerve conduction velocity. Although hindlimb grip strength of the 400 mg kg-1 group was significantly decreased by 17% relative to the vehicle controls on Day 15, this finding appeared related to the reduced food consumption and body weight gain in these animals. No microscopic changes were detected in peripheral nerves. Necrosis and proliferation of fibrillary astrocytes (gliosis) were seen in the cerebellum and medulla of the 400 mg kg-1 animals on Day 16. Gliosis in these same brain regions was observed in the 300 and 400 mg kg-1 groups on Day 44. The results show that intravenous administration of misonidazole to rats causes dose-limiting central nervous system toxicity without effects on peripheral nervous tissue. The lack of peripheral neurotoxicity was most likely due to a combination of several interrelated factors including route of administration, duration and intensity of the dosing regimen, and total cumulative dose.

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

PubMed

Sen, Sarbattama; Simmons, Rebecca A

2010-12-01

Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs.

PubMed

Jakob, S; Mosenthin, R; Thaela, M J; Weström, B R; Rehfeld, J F; Olsen, O; Karlsson, S; Ahrén, B; Ohlsson, A; Karlsson, B W; Pierzynowski, S G

2000-01-01

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered. Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and alpha-amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.v. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.

Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats.

PubMed

Rao, C V; Rivenson, A; Kelloff, G J; Reddy, B S

1995-01-01

The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids.

PubMed

Gunnarsson, David; Selstam, Gunnar; Ridderstråle, Yvonne; Holm, Lena; Ekstedt, Elisabeth; Madej, Andrzej

2009-12-10

Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids. Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3-4 mg/kg/day) for approximately 3 months. Plasma testosterone and total and free triiodothyronine (T3) concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA) was carried out. No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8) phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l). This elevation was preceded by a rise in plasma total T3 that occurred on September 17 (week 6). A slightly higher concentration of free T3 was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10) that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant. Our findings suggest that phytoestrogens can stimulate testosterone synthesis during puberty in male goats by increasing the secretion of T3; a hormone known to stimulate Leydig cell steroidogenesis. It is possible that feedback signalling underlies the tendency towards decreased steroid production at the end of the experiment.

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

PubMed Central

2009-01-01

Background Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids. Methods Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3 - 4 mg/kg/day) for ~3 months. Plasma testosterone and total and free triiodothyronine (T3) concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA) was carried out. Results No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8) phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l). This elevation was preceded by a rise in plasma total T3 that occurred on September 17 (week 6). A slightly higher concentration of free T3 was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10) that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant. Conclusion Our findings suggest that phytoestrogens can stimulate testosterone synthesis during puberty in male goats by increasing the secretion of T3; a hormone known to stimulate Leydig cell steroidogenesis. It is possible that feedback signalling underlies the tendency towards decreased steroid production at the end of the experiment. PMID:20003293

[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol].

PubMed

Pintos, Patricia Mabel; Lezón, Christian Esteban; Bozzini, Clarisa; Friedman, Silvia María; Boyer, Patricia Mónica

2013-01-01

Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution. To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress. Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups. Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05). These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Low-tar and high-tar cigarettes

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

Holt, P.G.; Chalmer, J.E.; Roberts, L.M.

Mice were exposed for 7 to 8 minutes on weekdays to fresh smoke from high-tar (HT) or low-tar (LT) cigarettes for varying periods of up to 36 weeks. Mice exposed to HT cigarettes exhibited more marked alterations in humoral immune responsiveness, hematological profiles, and pulmonary pathologic findings than those exposed to LT cigarettes. However, cell-mediated immune responsiveness to both bacterial and tumor-specific antigens was depressed similarly in animals exposed to HT or LT cigarettes. Furthermore, the growth rates of subcutaneously established tumors were enhanced similarly in the two groups, with respect to those in control animals.

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…

Trick-or-Treat Candy-Getters and Hornet Scare Devices: Second Graders Make Creative Inventions Related to Animal Adaptations

ERIC Educational Resources Information Center

Rule, Audrey C.; Baldwin, Samantha; Schell, Robert

2009-01-01

This repeated measures study examined second graders' (n = 21) performance in creating inventions related to animal adaptations for simple products under two conditions that alternated each week for a six-week period. In the analogy condition, students used form and function analogy object boxes to learn about animal adaptations, applying these…

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

PubMed

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

2015-02-04

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

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

Reversibility and safety of KISS1 metastasis suppressor gene vaccine in immunocastration of ram lambs

PubMed Central

2018-01-01

Objective The aim of this study was to investigate the reversibility and safety of KISS1 metastasis suppressor (KISS1) gene vaccine in immunocastration. Methods Six eight-week old ram lambs were randomly divided into vaccinated and control groups. The vaccine (1 mg/ram lamb) was injected at weeks 0, 3, and 6 of the study. Blood samples were collected from the jugular vein before primary immunization and at weeks 2, 4, 6, 10, 14, 22, and 30 after primary immunization. All ram lambs were slaughtered at 38 weeks of age, and samples were collected. Results The specific anti-KISS1 antibody titers in vaccinated animals were significantly higher and the serum testosterone level was significantly lower than those in the control groups from week 4 to 14 after primary immunization (p<0.05). No significant difference was observed at weeks 22 and 30 after the primary immunization. Similar results were also found for scrotal circumference, testicular weight, length, breadth, and spermatogenesis in seminiferous tubules in week 30 after primary immunization. KS (KISS1-hepatitis B surface antigen S) fusion fragment of KISS1 gene vaccine was not detected in host cell genomic DNA of 9 tissues of the vaccinated ram lambs by polymerase chain reaction. Conclusion The effects of KISS1 gene vaccine in immunocastration were reversible and no integration events were recorded. PMID:29268573

Reversibility and safety of KISS1 metastasis suppressor gene vaccine in immunocastration of ram lambs.

PubMed

Han, Yan-Guo; Liu, Gui-Qiong; Jiang, Xun-Ping; Xiang, Xing-Long; Huang, Yong-Fu; Nie, Bin; Zhao, Jia-Yu; Nabeel, Ijaz; Tesema, Birhanu

2018-06-01

The aim of this study was to investigate the reversibility and safety of KISS1 metastasis suppressor ( KISS1 ) gene vaccine in immunocastration. Six eight-week old ram lambs were randomly divided into vaccinated and control groups. The vaccine (1 mg/ram lamb) was injected at weeks 0, 3, and 6 of the study. Blood samples were collected from the jugular vein before primary immunization and at weeks 2, 4, 6, 10, 14, 22, and 30 after primary immunization. All ram lambs were slaughtered at 38 weeks of age, and samples were collected. The specific anti- KISS1 antibody titers in vaccinated animals were significantly higher and the serum testosterone level was significantly lower than those in the control groups from week 4 to 14 after primary immunization (p<0.05). No significant difference was observed at weeks 22 and 30 after the primary immunization. Similar results were also found for scrotal circumference, testicular weight, length, breadth, and spermatogenesis in seminiferous tubules in week 30 after primary immunization. KS ( KISS1 -hepatitis B surface antigen S ) fusion fragment of KISS1 gene vaccine was not detected in host cell genomic DNA of 9 tissues of the vaccinated ram lambs by polymerase chain reaction. The effects of KISS1 gene vaccine in immunocastration were reversible and no integration events were recorded.

Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

PubMed Central

2012-01-01

Background Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice. Methods and results Eight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p<0.001). Inflammation measured by mRNA expressions of IL-6, MMP-9, PAI-1 and leptin and protein expression of NF-κB was higher, whereas anti-inflammation measured by mRNA expressions of adiponectin and INF-γ was lower in obesity than in control and OR (all p<0.003). Oxidative protein expressions of NOX-1, NOX-2 and oxidized protein were higher, whereas expression of anti-oxidant markers HO-1 and NQO-1 were lower (all p<0.01); and apoptosis measured by Bax and caspase 3 was higher, whereas anti-apoptotic Bcl-2 was lower in obesity as compared with control and OR (all p<0.001). The expressions of fibrotic markers phosphorylated Smad3 and TGF-β were higher, whereas expression of anti-fibrotic phosphorylated Smad1/5 and BMP-2 were lower (all p<0.02); and LVEF was lower, whereas the LV remodeling was higher in obesity than in control and OR (all p<0.001). Conclusion Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity. PMID:22784636

Individual differences in the forced swimming test and the effect of environmental enrichment: searching for an interaction.

PubMed

Sequeira-Cordero, A; Mora-Gallegos, A; Cuenca-Berger, P; Fornaguera-Trías, J

2014-04-18

Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the exposure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals' individuality can somehow modulate the response to environmental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8weeks. Animals were subjected to the open field test (OFT) before and 6weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched animals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accumbens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expression data, however, an effect of enrichment on accumbal corticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a number of differences between animals with low and high immobility or animals housed in standard and enriched conditions, but also suggested that animals' individuality modulated in some way the response to environmental stimuli. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats.

PubMed Central

Larsson, L; Li, X; Teresi, A; Salviati, G

1994-01-01

1. The effects of 4 weeks of thyroid hormone treatment on contractile, enzyme-histochemical and morphometric properties and on the myosin isoform composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscle in young (3-6 months) and old (20-24 months) male rats. 2. In the soleus of untreated controls, contraction and half-relaxation times of the isometric twitch increased by 19-32% with age. The change in contractile properties was paralleled by an age-related increase in the proportions of type I fibres and type I myosin heavy chain (MHC) and slow myosin light chain (MLC) isoforms. 3. In the EDL of controls, contraction and half-relaxation times were significantly prolonged (21-38%) in the post-tetanus twitch in the old animals. No significant age-related changes were observed in enzyme-histochemical fibre-type proportions, although the number of fibres expressing both type IIA and IIB MHCs and of fibres expressing slow MLC isoforms was increased in the old animals. 4. Serum 3,5,3',5'-tetraiodothyronine (T4) levels were lower (34%) in the old animals, but the primary byproduct of T4, 3,5,3'-triiodothyronine (T3), did not differ between young and old animals. 5. The effects of 4 weeks of thyroid hormone treatment were highly muscle specific, and were more pronounced in soleus than in EDL, irrespective of animal age. In the soleus, this treatment shortened the contraction and half-relaxation times by 35-57% and decreased the number of type I fibres by 66-77% in both young and old animals. In EDL, thyroid hormone treatment significantly shortened the contraction time by 24%, but the change was restricted to the old animals. 6. In conclusion, the ability of skeletal muscle to respond to thyroid hormone treatment was not impaired in old age and the age-related changes in speed of contraction and enzyme-histochemical properties and myosin isoform compositions were diminished after thyroid hormone treatment in both the soleus and EDL. Images Figure 3 Figure 4 PMID:7853237

SU-C-204-07: Radiation Therapy as a Potential Treatment for Obesity: Initial Data from a Preclinical Investigation

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

Pasciak, A; Bradley, Y; Nodit, L

Purpose: To evaluate the feasibility of Yttrium-90 (90Y) radionuclide therapy as a potential treatment for obesity in a porcine model. As the only appetite-stimulating hormone, localized targeting of ghrelin-producing X/A cells in the fundus of the stomach using 90Y may reduce serum ghrelin levels and decrease hunger. Methods: Under approval of the University of Tennessee IACUC, 8 young female pigs aged 12–13 weeks and weighing 21.8–28.1 Kg were included in this study. Six animals underwent transfemoral angiography as part of a two-day procedure involving: (1) infusion of 99mTc-MAA, followed by nuclear scintigraphy and contrast-enhanced CT for treatment-planning and (2) administrationmore » of resin 90Y microspheres into the stomach fundus. Calibrated 90Y activities were infused into the main left gastric and the gastric artery arising from the splenic to yield predetermined fundal absorbed doses. Control animals underwent a sham procedure with saline and contrast. Weekly animal weight and serum ghrelin were measured along with post-euthanasia histologic analyses of mucosal integrity and ghrelin immunoreactive cell-density. Results: 90Y radioembolization was administered to six pigs in dosages from 46.3 to 105.1 MBq resulting in average fundal absorbed doses between 35.5 and 91.9 Gy. No animal showed any signs of pain or GI complication through the duration of the study. Ghrelin immunoreactive cell-density was significantly lower in treated vs. control animals in both the stomach fundus (13.5 vs 34.8, P < 0.05) and body (11.2 vs 19.8, P < 0.05). A trend towards decreased weight gain in treated animals as well as a decrease in explanted stomach volume was also noted. Conclusion: The safety and technical feasibility of radiation therapy using 90Y radioembolization as a potential treatment for obesity has been demonstrated at fundal absorbed doses over 90 Gy. Preliminary data is suggestive of short-term safety and potential efficacy, however, further animal studies are required. Project was funded by SIRTex medical ltd.« less

Early mechanical stimulation only permits timely bone healing in sheep.

PubMed

Tufekci, Pelin; Tavakoli, Aramesh; Dlaska, Constantin; Neumann, Mirjam; Shanker, Mihir; Saifzadeh, Siamak; Steck, Roland; Schuetz, Michael; Epari, Devakar

2018-06-01

Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

In Vivo Caprine Model for Osteomyelitis and Evaluation of Biofilm-Resistant Intramedullary Nails

PubMed Central

Tran, Nhiem; Tran, Phong A.; Jarrell, John D.; Engiles, Julie B.; Thomas, Nathan P.; Young, Matthew D.; Hayda, Roman A.; Born, Christopher T.

2013-01-01

Bone infection remains a formidable challenge to the medical field. The goal of the current study is to evaluate antibacterial coatings in vitro and to develop a large animal model to assess coated bone implants. A novel coating consisting of titanium oxide and siloxane polymer doped with silver was created by metal-organic methods. The coating was tested in vitro using rapid screening techniques to determine compositions which inhibited Staphylococcus aureus growth, while not affecting osteoblast viability. The coating was then applied to intramedullary nails and evaluated in vivo in a caprine model. In this pilot study, a fracture was created in the tibia of the goat, and Staphylococcus aureus was inoculated directly into the bone canal. The fractures were fixed by either coated (treated) or non-coated intramedullary nails (control) for 5 weeks. Clinical observations as well as microbiology, mechanical, radiology, and histology testing were used to compare the animals. The treated goat was able to walk using all four limbs after 5 weeks, while the control was unwilling to bear weight on the fixed leg. These results suggest the antimicrobial potential of the hybrid coating and the feasibility of the goat model for antimicrobial coated intramedullary implant evaluation. PMID:23841085

Safety and Efficacy of Topical Lime Sulfur in Mice Infested with Myocoptes musculinus

PubMed Central

Wood, Jennifer S; Courtney, Cynthia L; Lieber, Karen A; Lee, Vanessa K

2013-01-01

Current treatment options for murine fur mites have limitations in safety and efficacy. This study evaluated whether topical lime sulfur (LS) is an adjunct or alternative to traditional treatment options for Myocoptes musculinus. To evaluate the safety of topical LS, mice were dipped in a 3% LS solution at 34 and 41 d of age. Mice were observed daily for side effects and mortality, with blood work and necropsy at 42 d of age to evaluate for pathologic changes. To determine the efficacy of topical LS, postweanling mice infested with M. musculinus were treated with LS once weekly for 2 wk and then housed with uninfested sentinel mice for 4 wk. Weekly tape tests and postmortem tape tests and skin scrapings were performed on all mice. Treated postweanling mice had significantly lower Hgb levels and higher BUN levels than did control animals. In mite-infested mice, the number of positive cages at euthanasia was the same between treated and control animals. Although topical LS did not cause gross or microscopic changes to organ systems, it may cause clinicopathologic changes, and topical LS is not effective as a sole treatment for M. musculinus infestation of postweanling mice. PMID:23849408

Effect of Sodium Arsenite on Mouse Skin Carcinogenesis.

PubMed

Palmieri, Mónica A; Molinari, Beatriz L

2015-07-01

Arsenic is carcinogenic in human beings, and environmental exposure to arsenic is a public health issue that affects large populations worldwide. Thus, studies are needed to determine the mode of action of arsenic and prevent harmful effects arising from arsenic intake. The present study assessed the influence of sodium arsenite (As(3+)) on potentially carcinogenic processes that are either pre-existing or concomitant with chronic intake of water containing As(3+). Experiments using SenCar mice were designed to evaluate the effect of chronic administration of As(3+) (2, 20, or 200 mg of As(3+)/L) in drinking water that overlapped to varying degrees with a 2-stage carcinogenesis protocol carried out over 9 months. The results showed a time-dependent pattern. During early stages of carcinogenesis (6-12 weeks), animals exposed to As(3+) and the carcinogenesis protocol showed increased numbers of tumors compared to control animals. During late carcinogenesis (16-30 weeks), the number of tumors stabilized to below control values, but the tumors showed increased malignancy. These findings indicate that the outcomes of the 2-stage skin carcinogenesis protocol are modified by the presence of arsenite in drinking water, which increases the rate of carcinoma development. © 2015 by The Author(s).

The effect of increased ozone concentrations in the air on selected aspects of rat reproduction.

PubMed

Jedlińska-Krakowska, M; Gizejewski, Z; Dietrich, G J; Jakubowski, K; Glogowski, J; Penkowski, A

2006-01-01

Five-month-old male rates were exposed to 0.5 ppm ozone for 50 days, 5 hours a day. A week before the completion of ozone exposure, a biological test was performed to determine the fertilization rate and the survival rate of newborns in both ozone-exposed and control animals. After 50 days, the rats were sacrificed with an overdose of halotane, and testes were collected to assess the morphology and motility of spermatozoa. Neither the morphology of spermatozoa nor motility parameters determined by the CASA (computer-assisted sperm analysis) system showed statistically significant differences between ozone-exposed and control males. The number of successful matings and the survival rate of newborns per litter within one year postpartum were also similar in both groups. However, sperm concentration was by 17% lower in ozone-exposed rats, compared with the control animals.

Places to Go; People to See; Things to Do--Celebrating Be Kind to Animals Week.

ERIC Educational Resources Information Center

Holden, Lorraine P.

1984-01-01

Presents suggestions of what teachers and employees of welfare organizations can do to encourage people's observance of "Be Kind to Animals Week." Includes places to go, people to see, and things to do. (BC)

The use of α- or β-blockers to ameliorate the chronic stress of captivity in the house sparrow (Passer domesticus).

PubMed

Fischer, Clare Parker; Romero, L Michael

2016-01-01

When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows ( Passer domesticus ) over the first week of captivity. The birds were treated with saline, propranolol (a β-blocker) or phentolamine (an α-blocker) for the first 3 days of captivity. We also compared newly captured animals with animals that had been held in captivity for 1 month. During the first week of captivity, baseline corticosterone increased, but that increase was blocked by propranolol. Heart rate was not different between the treatment groups, but it was higher during the first week than after 1 month in captivity. Sympathetic nervous system activity (as measured by heart rate variability) decreased over the first week of captivity, but was not affected by treatment. β-Blockers, but not α-blockers, might help to improve some symptoms of chronic stress in newly captured animals.

Involvement of Indian hedgehog signaling in mesenchymal stem cell-augmented rotator cuff tendon repair in an athymic rat model.

PubMed

Zong, Jian-Chun; Mosca, Michael J; Degen, Ryan M; Lebaschi, Amir; Carballo, Camila; Carbone, Andrew; Cong, Guang-Ting; Ying, Liang; Deng, Xiang-Hua; Rodeo, Scott A

2017-04-01

Bone marrow aspirate has been used in recent years to augment tendon-to-bone healing, including in rotator cuff repair. However, the healing mechanism in cell-based therapy has not been elucidated in detail. Sixteen athymic nude rats were randomly allocated to 2 groups: experimental (human mesenchymal stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing enthesis. Macrophages were identified using CD68 and CD163 staining, and proliferating cells were identified using proliferating cell nuclear antigen staining. More organized and stronger staining for collagen II and a higher abundance of SOX9 + cells were observed at the enthesis in the experimental group at 2 weeks. There was significantly higher Gli1 and Patched1 expression in the experimental group at the enthesis at 2 weeks and higher numbers of Ihh + cells in the enthesis of the experimental group vs control at both 2 weeks and 4 weeks postoperatively. There were more CD68 + cells localized to the tendon midsubstance at 2 weeks compared with 4 weeks, and there was a higher level of CD163 staining in the tendon midsubstance in the experimental group than in the control group at 4 weeks. Stem cell application had a positive effect on fibrocartilage formation at the healing rotator cuff repair site. Both SOX9 and Ihh signaling appear to play an important role in the healing process. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

The effect of East Coast fever immunisation and different acaricidal treatments on the productivity of beef cattle.

PubMed

Morzaria, S P; Irvin, A D; Wathanga, J; D'Souza, D; Katende, J; Young, A S; Scott, J; Gettinby, G

1988-09-17

A trial was performed on a farm in the Coast Province of Kenya to study the effects of East Coast fever immunisation and different acaricidal treatments on the productivity of immunised and unimmunised beef cattle. Eighty cattle were immunised against Theileria parva parva (Marikebuni) by the infection and treatment method and a similar group was left as an unimmunised control. Immunisation had no deleterious effect on the cattle. After immunisation, the immunised and control groups were each subdivided into four groups of 20 and each subgroup was managed under a different tick control regimen. The tick control regimen were, acaricidal spraying twice a week or once every three weeks, the application of acaricide-impregnated ear-tags, and no tick control. During a nine-month exposure period there were 18 cases of East Coast fever among the 80 immunised cattle, three which were severe and the others mild. Among the 80 unimmunised cattle there were 57 cases of East Coast fever, 50 of which were severe. The highest morbidity and mortality occurred in the groups under limited tick control or without tick control. Overall weight gain in the immunised cattle, irrespective of the tick control regimen, was better than the weight gain in the unimmunised groups. Within the immunised groups, the weight gain of the cattle sprayed twice weekly was comparable to the weight gain of the animals with acaricidal ear-tags and was significantly higher than the weight gains in the groups sprayed once every three weeks or with tick control. Preliminary cost/benefit analysis showed that it was uneconomical to maintain unimmunised cattle under limited or no tick control.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed Central

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

2017-01-01

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

Comparative Study of Ureteral Stents Following Endoureterotomy in the Porcine Model: 3 vs 6 Weeks and 7F vs 14F

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

Soria, Federico; Sanchez, Francisco M.; Sun, Fei

2005-12-15

The aim of the study was to determine the optimal stent size and stenting duration following retrograde endoureterotomy of experimental ureteral strictures. Twenty healthy Large White female pigs were randomly divided into four groups, depending on stent size (7F vs 14F) and stenting duration (3 weeks vs 6 weeks). Three additional pigs were used as the control group. The internal ureteral diameter was measured 2 cm below the lower pole of the right kidney. Histopathological changes of the urinary tract, ultrasonographic and fluoroscopic studies, urine culture, and serum urea and creatine levels were analyzed during the different phases of themore » study. The study was divided into three phases. Phase I included premodel documentation of the normal urinary tract and laparoscopic ureteral stricture creation. During the second phase 1 month later, the diagnosis and endourologic treatment of strictures were performed. Phase III began 4 weeks after stent removal; follow-up imaging studies and postmortem evaluation of all animals were performed. Ureteral strictures developed in all animals 4 weeks after model creation. Results from ureteral diameter measurements and pathological studies revealed no statistically significant intergroup differences. However, prevalence of urinary infection proved to be directly related to stent size (14F) and permanence (6 weeks). The chi square results suggest a statistically significant relationship between the urinary tract infection and recurrent strictures ({alpha} = 0.046). We recommend the use of 7F stents for a period of 3 weeks or less, as these are more easily positioned and result in the reduction of secondary side effects (lower infection rate, less intramural ureteral lesions). A significant relationship between urinary tract infection and stricture recurrence was found in this experimental study.« less

Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet.

PubMed

Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; García-Martínez, Betzabeth Anali; López-Muñoz, Francisco Javier

2016-10-05

Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception ("plantar test" method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestrogenic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8-100mg/kg p.o.), were evaluated in all groups. The administration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrophoresis of phosphoglycerate kinase-2 to determine testicular damage induced by ethylene glycol monomethyl ether and sterility associated with chromosomal abnormality.

PubMed

Koizumi, A; Hamade, N; Arai, M; Takatoku, M; Yasuhiko, W; Tsukada, M; Kamiyama, S

1990-01-01

Phosphoglycerate kinase (PGK, EC 2.7.2.3), which is expressed specifically in sperm and spermatids, is an enzyme in the Embden-Meyerhof pathway that converts glucose to pyruvate. We developed an electrophoresis method to determine relative PGK-2 quantity and applied it to evaluate spermatogenesis activity. In the ethylene glycol monomethyl ether (EGME)-induced testicular toxicity, relative PGK-2 quantity had not decreased until 4 weeks of exposure. Mean relative PGK-2 quantities, defined as PGK-2 quantity over PGK-1 quantity in a pooled spleen sample (+/- SD) were: 1.43 +/- 0.32 for control animals (N = 10); 1.67 +/- 0.24 for the group exposed at 500 mg/kg for 5 days (N = 6); 1.85 +/- 0.58 for the group exposed at 500 mg/kg for 2 weeks (N = 6); 0.09 +/- 0.06 for the group exposed at 500 mg/kg for 4 weeks (N = 6); not detectable in animals exposed at 500 mg/kg for 5 weeks (N = 7); 0.208 +/- 0.103 for the group exposed at 250 mg/kg for 5 weeks (N = 6); and 1.35 +/- 0.38 for the group exposed at 125 mg/kg for 5 weeks (N = 6). These relative quantities showed a good correlation with sperm/spermatid counts (r = 0.823, p less than 0.01) and histological findings. These findings suggest that EGME has toxicity on primary spermatocytes and spermatogonia. In the case of sterility associated with a chromosomal abnormality (chromosomal translocation between chromosome X and 16), relative PGK-2 quantity was not detected in any of the seven adult (12 weeks of age) mice, although many primary spermatocytes were detected by histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

[Swim training attenuates myocardial remodeling and the pulmonary congestion in wistar rats with secondary heart failure to myocardial infarction].

PubMed

Portes, Leslie Andrews; Tucci, Paulo José Ferreira

2006-07-01

To evaluate the effects of swimming on pulmonary water content in animals with heart failure (HF) after myocardial infarction (MI). After coronary occlusion, MI size 20% 40% of the LV large. The animals swam for 60 min/day, 5 days/week for 8 weeks. The wet weight of lung, liver, atriums, LV and right ventricle (RV) as well as the dry weight of the liver and lung were determined. ANOVA and Tukey test were used for statistical analysis. An increase in the atrium/body weight ratio was noted in the sedentary animals with moderate (MImod-SED: n=8) and large (MIlg-SED: n=10) infarctions in comparison to the sedentary control (C-SED: n=14) and trained (C-TR: n=16) rats. An increase in the RV/body weight and LV/body weight ratios was noted in the MIlg-SED. The heart/body weight ratio was higher in MIlg-SED when compared to the other groups. The infarcted trained animals presented diminished hypertrophy. The pulmonary water content was higher in MIlg-SED animals (81+/-0.4%) than in C-SED animals (79+/-0.4%). No differences were found for the other comparisons (C-TR: 79+/-0.4%; MImod-SED: 80+/-0.3%; MImod-TR: 80+/-0.6%; MIlg-TR: 79+/-0.7%). The increase of cardiac mass and pulmonary water content presented by MIlg-SED was diminished in the trained animals. The results suggest that the practice of physical exercise can diminish HF and contribute to favorable cardiac remodeling.

Long-term exposure of several marine benthic animals to static magnetic fields.

PubMed

Bochert, R; Zettler, M L

2004-10-01

Electrical currents in underwater sea cables could induce magnetic fields. The sea cables lie on or within the sea bottom and this is the living area for many invertebrate and vertebrate species. North Sea prawn Crangon crangon (Crustacea, Decapoda), round crab Rhithropanopeus harrisii (Crustacea, Brachyura), glacial relict isopod Saduria entomon (Crustacea, Isopoda), blue mussel Mytilus edulis (Bivalvia), and young flounder Plathichthys flesus (Pisces) were exposed to a static magnetic field (MF) of 3.7 mT for several weeks. The results showed no differences in survival between experimental and control animals. Mussels M. edulis were kept under static magnetic field conditions for 3 months during their reproductive period in spring. The determination of gonad index and condition index revealed no significant differences to the control group. 2004 Wiley-Liss, Inc.

Hypocretin Receptor Expression in Canine and Murine Narcolepsy Models and in Hypocretin-Ligand Deficient Human Narcolepsy

PubMed Central

Mishima, Kazuo; Fujiki, Nobuhiro; Yoshida, Yasushi; Sakurai, Takeshi; Honda, Makoto; Mignot, Emmanuel; Nishino, Seiji

2008-01-01

Study Objective: To determine whether hypocretin receptor gene (hcrtR1 and hcrtR2) expression is affected after long-term hypocretin ligand loss in humans and animal models of narcolepsy. Design: Animal and human study. We measured hcrtR1 and hcrtR2 expression in the frontal cortex and pons using the RT-PCR method in murine models (8-week-old and 27-week-old orexin/ataxin-3 transgenic (TG) hypocretin cell ablated mice and wild-type mice from the same litter, 10 mice for each group), in canine models (8 genetically narcoleptic Dobermans with null mutations in the hcrtR2, 9 control Dobermans, 3 sporadic ligand-deficient narcoleptics, and 4 small breed controls), and in humans (5 narcolepsy-cataplexy patients with hypocretin deficiency (average age 77.0 years) and 5 control subjects (72.6 years). Measurement and Results: 27-week-old (but not 8-week-old) TG mice showed significant decreases in hcrtR1 expression, suggesting the influence of the long-term ligand loss on the receptor expression. Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases. HcrtR2-mutated narcoleptic Dobermans (with normal ligand production) showed no alteration in hcrtR1 expression. Conclusions: Moderate declines in hcrtR expressions, possibly due to long-term postnatal loss of ligand production, were observed in hypocretin-ligand deficient narcoleptic subjects. These declines are not likely to be progressive and complete. The relative preservation of hcrtR2 expression also suggests that hypocretin based therapies are likely to be a viable therapeutic options in human narcolepsy-cataplexy. Citation: Mishima K; Fujiki N; Yoshida Y; Sakurai T; Honda M; Mignot E; Nishino S. Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy. SLEEP 2008;31(8):1119-1126. PMID:18714784

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2008-08-01

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

An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat.

PubMed

Mitchell, J M; Mengs, U; McPherson, S; Zijlstra, J; Dettmar, P; Gregson, R; Tigner, J C

2006-01-01

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

PubMed

Rivera, Francheska; Espino, Ana M

2016-01-01

Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells. Published by Elsevier Inc.

Delayed emergence of methamphetamine's enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence.

PubMed

Vaupel, D B; Schindler, C W; Chefer, S; Belcher, A M; Ahmet, I; Scheidweiler, K B; Huestis, M A; Stein, E A

2016-02-01

Methamphetamine abuse is linked with brain abnormalities, but its peripheral effects constitute an integral aspect of long-term methamphetamine use. Eight male rhesus monkeys with long histories of intravenous methamphetamine self-administration were evaluated 1 day, and 1, 4, 12, 26, and 52 weeks after their last methamphetamine self-administration session. On test days, isoflurane-anesthetized animals received a 0.35 mg/kg IV methamphetamine challenge. A control group consisted of 10 age and gender matched drug naïve monkeys. Cardiovascular responses to methamphetamine were followed for 2.5h. Echocardiograms were acquired at 3 and 12 months of abstinence and in the control animals. No pre-methamphetamine baseline differences existed among 7 physiological measures across all conditions and controls. As expected, methamphetamine increased heart rate and blood pressure in controls. However, immediately following the self-administration period, the blood pressure response to methamphetamine challenge was reduced when compared to control monkeys. The peak and 150-min average heart rate increases, as well as peak blood pressure increases following methamphetamine were significantly elevated between weeks 12 to 26 of abstinence. These data indicate the development of tolerance followed by sensitization to methamphetamine cardiovascular effects. Echocardiography demonstrated decreased left ventricular ejection fraction and cardiac output at 3 months of abstinence. Importantly, both cardiovascular sensitization and cardiotoxicity appeared to be reversible as they returned toward control group levels after 1 year of abstinence. Enhanced cardiovascular effects may occur after prolonged abstinence in addicts relapsing to methamphetamine and may underlie clinically reported acute cardiotoxic events. Published by Elsevier Ireland Ltd.

Delayed emergence of methamphetamine’s enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence

PubMed Central

Vaupel, DB; Schindler, CW; Chefer, S; Belcher, AM; Ahmet, I; Scheidweiler, KB; Huestis, MA; Stein, EA

2015-01-01

Background Methamphetamine abuse is linked with brain abnormalities, but its peripheral effects constitute an integral aspect of long-term methamphetamine use. Methods Eight male rhesus monkeys with long histories of intravenous methamphetamine self-administration were evaluated 1 day, and 1, 4, 12, 26, and 52 weeks after their last methamphetamine self-administration session. On test days, isoflurane-anesthetized animals received a 0.35 mg/kg IV methamphetamine challenge. A control group consisted of 10 age and gender matched drug naïve monkeys. Cardiovascular responses to methamphetamine were followed for 2.5 h. Echocardiograms were acquired at 3 and 12 months of abstinence and in the control animals. Results No pre-methamphetamine baseline differences existed among 7 physiological measures across all conditions and controls. As expected, methamphetamine increased heart rate and blood pressure in controls. However, immediately following the self-administration period, the blood pressure response to methamphetamine challenge was reduced when compared to control monkeys. The peak and 150-min average heart rate increases, as well as peak blood pressure increases following methamphetamine were significantly elevated between weeks 12 to 26 of abstinence. These data indicate the development of tolerance followed by sensitization to methamphetamine cardiovascular effects. Echocardiography demonstrated decreased left ventricular ejection fraction and cardiac output at 3 months of abstinence. Importantly, both cardiovascular sensitization and cardiotoxicity appeared to be reversible as they returned toward control group levels after 1 year of abstinence. Conclusions Enhanced cardiovascular effects may occur after prolonged abstinence in addicts relapsing to methamphetamine and may underlie clinically reported acute cardiotoxic events. PMID:26775284

Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair.

PubMed

Kovacevic, David; Fox, Alice J; Bedi, Asheesh; Ying, Liang; Deng, Xiang-Hua; Warren, Russell F; Rodeo, Scott A

2011-04-01

Rotator cuff tendon heals by formation of an interposed zone of fibrovascular scar tissue. Recent studies demonstrate that transforming growth factor-beta 3 (TGF-β(3)) is associated with tissue regeneration and "scarless" healing, in contrast to scar-mediated healing that occurs with TGF-β(1). Delivery of TGF-β(3) in an injectable calcium-phosphate matrix to the healing tendon-bone interface after rotator cuff repair will result in increased attachment strength secondary to improved bone formation and collagen organization and reduced scar formation of the healing enthesis. Controlled laboratory study. Ninety-six male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon followed by acute repair using transosseous suture fixation. Animals were allocated into 1 of 3 groups: (1) repair alone (controls, n = 32), (2) repair augmented by application of an osteoconductive calcium-phosphate (Ca-P) matrix only (n = 32), or (3) repair augmented with Ca-P matrix + TGF-β(3) (2.75 µg) at the tendon-bone interface (n = 32). Animals were euthanized at either 2 weeks or 4 weeks postoperatively. Biomechanical testing of the supraspinatus tendon-bone complex was performed at 2 and 4 weeks (n = 8 per group). Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometry and immunohistochemical localization of collagen types I (COLI) and III (COLIII). Statistical analysis was performed using 2-way analysis of variance with significance set at P < .05. There was significantly greater load to failure of the Ca-P matrix + TGF-β(3) group compared with matrix alone or untreated controls at 4 weeks postoperatively (P = .04). At 2 weeks, microcomputed tomography revealed a larger volume of newly formed bone present at the healing enthesis in both experimental groups compared with the control group. By 4 weeks, this newly formed, woven bone had matured into calcified, lamellar bone. Histomorphometric analysis demonstrated significantly greater fibrocartilage and increased collagen organization at the healing tendon-bone insertion site in both experimental groups compared with the control group at 2 weeks (P = .04). Over time, TGF-β(3) delivery led to greater COLI expression compared with COLIII at the healing enthesis, indicating a more favorable COLI to COLIII ratio with administration of TGF-β(3). Augmentation with an osteoconductive Ca-P matrix at the tendon-bone repair site is associated with new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface in the early postoperative period after rotator cuff repair. The addition of TGF-β(3) significantly improved strength of the repair at 4 weeks postoperatively and resulted in a more favorable COLI/COLIII ratio. The delivery of TGF-β(3) with an injectable Ca-P matrix at the supraspinatus tendon footprint has promise to improve healing after soft tissue repair.