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Sample records for adrenalectomized adx rats

  1. Loss of fatty acid control of gluconeogenesis and PDH complex flux in adrenalectomized rats.

    PubMed

    Ciprés, G; Urcelay, E; Butta, N; Ayuso, M S; Parrilla, R; Martín-Requero, A

    1994-10-01

    This work aimed to determine the role played by the adrenal gland in the fatty acid control of gluconeogenesis in isolated perfused rat livers. The gluconeogenic substrate concentration responses were not altered in adrenalectomized (ADX) rats. This observation indicates that glucocorticoids are not essential to maintain normal basal gluconeogenic rates. In contrast, fatty acid failed to stimulate gluconeogenesis from lactate and elicited attenuated stimulation with pyruvate as substrate in livers from ADX rats. Fatty acid-induced stimulation of respiration and ketone body production were similar in control and ADX rats. Thus the diminished responsiveness of the gluconeogenic pathway to fatty acid cannot be the result of different rates of energy production and/or generation of reducing power. Fatty acids did not inhibit pyruvate decarboxylation in livers from ADX rats. Even though mitochondria isolated from livers of ADX rats showed normal basal rates of pyruvate metabolism, fatty acids failed to inhibit pyruvate decarboxylation and the activity of the pyruvate dehydrogenase complex. This novel observation of the glucocorticoid effect in controlling the pyruvate dehydrogenase complex responsiveness indicates that the mitochondrial partitioning of pyruvate between carboxylation and decarboxylation reactions may be altered in livers from ADX rats. We propose that the diminished effect of fatty acid in stimulating gluconeogenesis in livers from ADX rats is the result of a limited pyruvate availability for the carboxylase reaction due to a lack of inhibition of flux through the pyruvate dehydrogenase complex.

  2. Vascular Responsiveness in Adrenalectomized Rats with Corticosterone Replacement

    NASA Technical Reports Server (NTRS)

    Darlington, Daniel N.; Kaship, Kapil; Keil, Lanny C.; Dallman, Mary F.

    1989-01-01

    To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (-100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+O, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.

  3. Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

    NASA Technical Reports Server (NTRS)

    Darlington, Daniel N.; Chew, Gordon; Ha, Taryn; Keil, Lanny C.; Dallman, Mary F.

    1990-01-01

    Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to

  4. Fed, but not Fasted, Adrenalectomized Rats Survive the Stress of Hemorrhage and Hypovolemia

    NASA Technical Reports Server (NTRS)

    Darlington, Daniel N.; Neves, Robert B.; Ha, Taryn; Chew, Gordon; Dallman, Mary F.

    1990-01-01

    We have recently shown that conscious adrenalectomized rats exhibit nearly normal recovery of arterial blood pressure during the 5 h after hemorrhage. In those experiments, it appeared that a previous reduction in food intake might have compromised the recovery of blood pressure and increased mortality. These experiments were designed to test in conscious sham-adrenalectomized (control) and adrenalectomized rats prepared with indwelling arterial and venous cannulae: 1. The effects of a 20- to 24-h fast (compared to rats fed ab libitum) on the mobilization of plasma substrates and recovery of arterial blood pressure after a 15 ml/kg - 5 min hemorrhage, and 2. Vascular responsivity to pressor agents in fed or fasted groups before or 2 h after hemorrhage. In all rats hemorrhage resulted in decreased arterial pressure and heart rate. Arterial pressure recovered to near normal in both fed and fasted control groups and in the led adrenalectomized rats, and all of these rats survived for 24 h after stress. By contrast, in the fasted adrenalectomized rats, arterial pressure recovered only during the first 1.5 - 2 h and then failed, resulting in 100% mortality by 3-5 h. Compared to the other three groups, in which substrate levels either increased or remained fairly stable, plasma glucose and beta-hydoxybutyrate concentrations fell steadily, from 1.5-2 h after hemorrhage until death occurred in the fasted adrenalectomized rats. Basal ACTH concentrations were elevated cormpared to control values in both adrenalectomized groups (fed and fasted). Hemorrhage caused increases in plasma ACTH in all groups; the magnitude of the responses did not differ among the groups. The dilution of Evans' blue dve after hemorrhage (used as an index of fluid movement into the vascular space) was not different in contol and adrenalectomized rats (either fed or fasted). There were no differences in pressor responses to phenylephrine, vasopressin, or angiotensin-II between the fed and fasted

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

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  6. Effect of ether inhalation by adrenalectomized pregnant rats on the adrenal corticosterone concentration in norma, decapitated, and encephalectomized fetuses.

    PubMed

    Negellen-Perchellet, E; Cohen, A

    1975-01-01

    The influence of decapitation or encephalectomy (total removal of the brain leaving the pituitary in place) on the adrenal corticosterone concentration of the 20-day-old rat fetus has been studied in normal pregnant rats, in adrenalectomized pregnant rats, and in adrenalectomized pregnant rats subjected to the stress conditions of inhalation of ether for 40 min. Decapitation or encephalectomy of the fetus always results in a drop in adrenal corticosterone concentration within 4 h which is prevented in 15 min by injecting 3.2 mU of hog ACTH into the decapitated fetus. In mothers adrenalectomized in order to avoid a negative feedback reaction of maternal corticosteroids on the fetal pituitary-adrenal system, ether inhalation causes an important rise in adrenal corticosterone concentration in normal fetuses but not in decapitated or encephalectomized ones. Thus ether, which crosses the placental barrier, is a stressor agent for the fetal rat.

  7. Chronic administration of oxprenolol and metoprolol attenuate sympathetic cardiovascular responses only in non-adrenalectomized pithed rats.

    PubMed

    Vila, E; Badia, A

    1995-10-01

    1. Oxprenolol and metoprolol (30 mg kg-1) were injected intraperitoneally (i.p.) for 1 day (acute treatment) and 6 weeks (chronic treatment) to Sprague-Dawley rats. 2. Increases of mean blood pressure and heart rate to noradrenaline (0.1-10 micrograms kg-1) and to electrical stimulation (0.5 msec, supramax V, 0.25-5 Hz) of the entire sympathetic outflow were measured in non-adrenalectomized (acute and chronic) and adrenalectomized (chronic) pithed rats. 3. Acute beta-adrenoceptor antagonist administration was without effect on mean blood pressure and heart rate increases to noradrenaline and electrical stimulation. 4. Chronic administration with oxprenolol significantly diminished the stimulation-induced increases of mean blood pressure and heart rate in non-adrenalectomized pithed rats. 5. Increases in heart rate, elicited by stimulation of the entire sympathetic outflow in non-adrenalectomized but not in adrenalectomized pithed rats, were decreased by metoprolol treatment. Both treatments were without effect on noradrenaline responses. 6. These results indicate that chronic beta-adrenoceptor antagonist treatment is associated with a reduction in the cardiovascular responses to sympathetic nerve-stimulation. However, this mechanism only operates when adrenomedullary adrenaline is present to facilitate the noradrenaline release through activation of presynaptic beta 2-adrenoceptors.

  8. The GABAB Positive Allosteric Modulator, ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats.

    PubMed

    Augier, Eric; Dulman, Russell S; Damadzic, Ruslan; Pilling, Andrew; Hamilton, J Paul; Heilig, Markus

    2017-03-15

    GABAergic signaling is involved in modulating the reinforcing properties of alcohol, and GABAB receptors have been proposed as a potential target for clinical treatment of alcoholism. The orthosteric GABAB receptor agonist baclofen has been shown to suppress operant self-administration of alcohol in animals and alcohol use in alcohol dependent patients, but its utility is limited by a narrow therapeutic index. We tested the effects of ADX71441, a novel GABAB receptor positive allosteric modulator on alcohol-related behaviors in rats. We first assessed the effects of ADX71441 (1, 3, 10 and 30 mg/kg, I.P.) on both non-dependent and dependent male Wistar rats trained to self-administer 20% alcohol. We then determined the effects of ADX71441 on stress-induced as well as cue-induced relapse-like behavior. Finally, we sought to identify the brain regions through which ADX71441 may act to prevent relapse-like behavior by mapping the neuronal activation induced by stress-induced reinstatement of alcohol-seeking using c-Fos immunohistochemistry. ADX71441 dose-dependently decreased alcohol self-administration of both dependent and non-dependent animals, but its potency was higher in alcohol-dependent rats. Furthermore, both cue- and stress-induced alcohol seeking were blocked by the GABAB receptor positive allosteric modulator. Finally, pretreatment with 3 mg/kg of ADX71441 before stress-induced reinstatement significantly decreased c-Fos expression in a network of brain regions implicated in stress induced relapse, comprising the nucleus accumbens shell, the dorsal raphe nucleus and the medial prefrontal cortex. Our findings support a causal role of GABAB receptors in alcohol reinforcement and relapse to alcohol seeking. These effects are observed in the absence of significant sedative side effects. Jointly, these observations indicate that GABAB receptor positive allosteric modulators merit being tested clinically for the treatment of alcoholism. Our data also point to

  9. Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis?

    PubMed

    Laugero, K D; Bell, M E; Bhatnagar, S; Soriano, L; Dallman, M F

    2001-07-01

    Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH. Here, we show that ADX (but not sham-ADX) rats prefer to consume significantly more sucrose than saccharin. Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal. Our results suggest that the brains of ADX rats, cued by sucrose energy (but not by nonnutritive saccharin) maintain normal activity in systems that regulate neuroendocrine (hypothalamic-pituitary-adrenal), behavioral (feeding), and metabolic functions (fat deposition). We conclude that because sucrose ingestion, like glucocorticoid replacement, normalizes energetic and neuromodulatory effects of ADX, many of the actions of the steroids on the central nervous system under basal conditions may be indirect and mediated by signals that result from the metabolic effects of adrenal steroids.

  10. Potentiation of Hormonal Responses to Hemorrhage and Fasting, but not Hypoglycemia in Conscious Adrenalectomized Rats

    NASA Technical Reports Server (NTRS)

    Darlington, Daniel N.; Keil, Lanny C.; Dallman, Mary F.

    1989-01-01

    Bilateral adrenalectomy (ADRX) in rats removes the source of two major stress-responsive hormones, corticosterone and epinephrine. To test how ADRX rats with-stand stress, we performed the following experiments in adult male rats provided with indwelling femoral arterial and venous cannulae and either ADRX or sham-adrenalectomized (Sham) 3 days later and given 0.5% NaCl to drink. Five to 6 days after adrenal surgery the rats were studied after either a 15 ml/kg.5 min hemorrhage or after an overnight fast followed by insulin-induced hypoglycemia. In fed unstressed ADRX rats, basal mean arterial blood pressure was slightly decreased; heart rate was increased; blood volume, vasopressin, and oxytocin concentrations were not different from sham values; and renin and norepinephrine were significantly elevated. The recovery of arterial pressure after hemorrhage in the ADRX rats was similar to that in the sham group over a 5-h period; however, the responses of vasopressin and oxytocin were significantly greater, and those of renin and norepinephrine were markedly potentiated in the ADRX group. Heart rate recovered faster in the ADRX group and was elevated, compared to the sham value, for most of the 5-h period. Restitution of blood volume was attenuated in the ADRX group, although the restitution of plasma protein was not different between the groups. A significant difference in the change in plasma osmolality between groups after hemorrhage may account for the attenuated restitution of blood volume. After an overnight fast, which reduced blood volume in both groups of rats, the plasma renin concentration rose still further in ADRX rats; the differences in other measured variables observed between fed ADRX and sham groups remained the same. The insulin-induced 50% decrease in glucose caused minor effects on arterial blood pressure and heart rate and occasioned responses in renin and norepinephrine of similar magnitudes in the two groups. We conclude that in the absence of

  11. Insulin effect on amino acid uptake by unloaded rat hindlimb muscles

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    The effect of insulin on the uptake of alpha-amino-isobutyric acid (AIB) by unloaded rat hindlimb muscles was investigated using soleus and extensor digitorum longus (EDL) muscles from intact and adrenalectomized (ADX) rats that were tail-casted for six days. It was found that, at insulin levels above 0.00001 units/ml, the in vitro rate of AIB uptake by muscles from intact animals was stimulated more in the weight bearing muscles than in unloaded ones. In ADX animals, this differential response to insulin was abolished.

  12. Skeletal response to corticosteroid deficiency and excess in growing male rats

    NASA Technical Reports Server (NTRS)

    Li, M.; Shen, Y.; Halloran, B. P.; Baumann, B. D.; Miller, K.; Wronski, T. J.

    1996-01-01

    The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not

  13. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in Adrenalectomized Rats.

    PubMed

    Miller, Desinia B; Snow, Samantha J; Schladweiler, Mette C; Richards, Judy E; Ghio, Andrew J; Ledbetter, Allen D; Kodavanti, Urmila P

    2016-04-01

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent bilateral adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1 ppm), 4 h/day for 1 or 2 days and responses assessed immediately postexposure. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to SHAM. Corticosterone tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED rats with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids (P = .15) and branched-chain amino acids increased after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX > DEMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not observed in DEMED and ADREX rats. We demonstrate that ozone-induced peripheral metabolic effects and lung injury/inflammation are mediated through adrenal-derived stress hormones likely via the activation of stress response pathway.

  14. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

  15. Corticosteroid induction of threat-induced behavioral inhibition in preweanling rats.

    PubMed

    Takahashi, L K; Rubin, W W

    1993-10-01

    Termination of ongoing behavior and assumption of defensive postures when threatened are adaptive characteristics of vertebrates. Altricial rat pups develop these characteristics by 14 days of age. At this time, pups inhibit their ultrasonic vocalizations and freeze when threatened. This emergence of behavioral inhibition is impaired when rats are adrenalectomized (ADX) at 10 days of age. That is, 14-day-old ADX pups exhibit deficits in freezing and continue to emit ultrasounds when confronted by an adult male rat. Studies also showed that removal of adrenal hormones does not potentiate vocalizations or render pups incapable of reducing their ultrasounds. More important, 3.0 mg/kg of corticosterone (CORT), but not lower doses, administered daily to ADX pups restored freezing, with lesser effects on ultrasound inhibition. Disrupting the developmental action of endogenous CORT appears to impair the ontogenetic expression of behavioral inhibition.

  16. Adrenalectomy mediated alterations in adrenergic activation of adenylate cyclase in rat liver

    SciTech Connect

    El-Refai, M.; Chan, T.

    1986-05-01

    Adrenalectomy caused a large increase in the number of ..beta..-adrenergic binding sites on liver plasma membranes as measured by /sup 125/I-iodocyanopindolol (22 and 102 fmol/mg protein for control and adrenalectomized (ADX) rats). Concomitantly an increase in the number of binding sites for /sup 3/H-yohimbine was also observed (104 and 175 fmol/mg protein for control and adx membranes). Epinephrine-stimulated increase in cyclic AMP accumulation in isolated hepatocytes were greater in cells from ADX rats. This increase in ..beta..-adrenergic mediated action was much less than what may be expected as a result of the increase in the ..beta..-adrenergic binding in ADX membranes. In addition phenoxybenzamine (10 ..mu..M) further augmented this action of epinephrine in both control and ADX cells. To test the hypothesis that the increase in the number of the inhibitory ..cap alpha../sub 2/-adrenergic receptors in adrenalectomy is responsible for the muted ..beta..-adrenergic response, the authors injected rats with pertussis toxin (PT). This treatment may cause the in vivo ribosylation of the inhibitory binding protein (Ni). Adenylate cyclase (AC) activity in liver plasma membranes prepared from treated and untreated animals was measured. In contrast with control rats, treatment of ADX rats with PT resulted in a significant increase in the basal activity of AC (5.5 and 7.7 pmol/mg protein/min for untreated and treated rats respectively). Isoproterenol (10 ..mu..M), caused AC activity to increase to 6.5 and 8.4 pmol/mg protein/min for membranes obtained from ADX untreated and ADX treated rats respectively. The ..cap alpha..-adrenergic antagonists had no significant effect on the ..beta..-adrenergic-mediated activation of AC in liver plasma membranes from PT treated control and ADX rats. The authors conclude that the ..beta..-adrenergic activation of AC is attenuated by Ni protein both directly and as a result of activation of ..cap alpha..-adrenergic receptors.

  17. Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.

    1989-01-01

    The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.

  18. ADX - Advanced Divertor and RF Tokamak Experiment

    NASA Astrophysics Data System (ADS)

    Greenwald, Martin; Labombard, Brian; Bonoli, Paul; Irby, Jim; Terry, Jim; Wallace, Greg; Vieira, Rui; Whyte, Dennis; Wolfe, Steve; Wukitch, Steve; Marmar, Earl

    2015-11-01

    The Advanced Divertor and RF Tokamak Experiment (ADX) is a design concept for a compact high-field tokamak that would address boundary plasma and plasma-material interaction physics challenges whose solution is critical for the viability of magnetic fusion energy. This device would have two crucial missions. First, it would serve as a Divertor Test Tokamak, developing divertor geometries, materials and operational scenarios that could meet the stringent requirements imposed in a fusion power plant. By operating at high field, ADX would address this problem at a level of power loading and other plasma conditions that are essentially identical to those expected in a future reactor. Secondly, ADX would investigate the physics and engineering of high-field-side launch of RF waves for current drive and heating. Efficient current drive is an essential element for achieving steady-state in a practical, power producing fusion device and high-field launch offers the prospect of higher efficiency, better control of the current profile and survivability of the launching structures. ADX would carry out this research in integrated scenarios that simultaneously demonstrate the required boundary regimes consistent with efficient current drive and core performance.

  19. Ultrastructure of rat initial collecting tubule. Effect of adrenal corticosteroid treatment.

    PubMed Central

    Stanton, B; Janzen, A; Klein-Robbenhaar, G; DeFronzo, R; Giebisch, G; Wade, J

    1985-01-01

    This study examines the effects of adrenalectomy and physiological replacement of mineralocorticoids and glucocorticoids on the cellular ultrastructure of the rat initial collecting tubule (late distal tubule). Animals were adrenalectomized (ADX) and for 10 d received by osmotic minipump either: vehicle, aldosterone (0.5 micrograms X 100 g-1 X d-1), aldosterone (2.0 micrograms X 100 g-1 X d-1), dexamethasone (1.2 micrograms X 100 g-1 X d-1), or aldosterone (0.5 micrograms X 100 g-1 X d-1) with dexamethasone (1.2 micrograms X 100 g-1 X d-1). Radioimmunoassay revealed that the low dose of aldosterone restored plasma aldosterone to control levels. The higher dose of aldosterone increased plasma levels by threefold. Morphometric techniques were used to measure membrane length of individual principal and intercalated cells in each condition. The basolateral membrane length of principal cells decreased by 35% in ADX animals. Low dose aldosterone replacement (0.5 micrograms X 100 g-1 X d-1) in ADX animals maintained membrane length at control values; at a higher level of aldosterone (2.0 micrograms X 100 g-1 X d-1) membrane length increased by 111% compared with control. Dexamethasone treatment, at a level that restored glomerular filtration rate to normal, had no effect on cellular ultrastructure. Combined aldosterone and dexamethasone replacement had no greater effect on basolateral membrane length than aldosterone alone. The length of the luminal membrane of the principal cell type was not affected by ADX or hormone treatment. Intercalated cell membrane length was not affected by ADX or hormone replacement. Thus, chronic aldosterone levels have an important, selective effect on the basolateral membrane of the principal cell. The correlation between these morphological results and the steroid hormone effects on renal electrolyte excretion, reported in the companion paper (15), suggests that basolateral membrane length is an important factor controlling the rate of

  20. Characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decreases in dexamethasone binding to rat hepatic cytosolic glucocorticoid receptor.

    PubMed

    Sunahara, G I; Lucier, G W; McCoy, Z; Bresnick, E H; Sanchez, E R; Nelson, K G

    1989-08-01

    An investigation of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the liver cytosolic glucocorticoid receptor (GRc) in intact and adrenalectomized (ADX) rats, using equilibrium binding analysis, sucrose gradient sedimentation, and affinity labeling experiments, clearly demonstrated that TCDD significantly reduced the binding capacity (Bmax) of the hepatic GRc but did not alter the apparent equilibrium dissociation constant (Kd). This effect was maximal after 24 hr and was still present 22 days after treatment. Western blot analysis revealed that TCDD treatment did not cause a comparable decrease in the levels of immunodetectable receptor protein, which suggests that the steroid-binding properties of the hepatic GRc are altered, rather than the absolute concentration of receptor protein. Studies of TCDD effects on the uptake of GRc by nuclei indicated that TCDD treatment did not alter the ability of the steroid-GRc complex to be taken up by nuclei; however, TCDD treatment did increase the total capacity of liver nuclei to bind steroid-GRc complexes. TCDD dose-response studies that compared the hepatic GRc steroid binding of ADX and intact rats indicated that adrenalectomy markedly enhanced the response to TCDD. Significant effects on the GRc binding in ADX animals were induced at TCDD doses that were 10,000 times lower than those required for a response in intact rats. Analysis of two other biochemical markers demonstrated that ADX rats were 10-fold more sensitive to the induction of microsomal benzo[a]pyrene hydroxylase but of similar sensitivity to reduction of epidermal growth factor receptor binding, when compared with the responses of intact animals. These data indicate that adrenal status may be important in modulating the responses of the animals to TCDD and that the alteration of the hepatic GRc pathway may have a role in some of the actions of TCDD.

  1. Evaluation of peripheral versus central effects of GABAB receptor activation using a novel, positive allosteric modulator of the GABAB receptor ADX71943, a pharmacological tool compound with a fully peripheral activity profile

    PubMed Central

    Kalinichev, M; Donovan-Rodriguez, T; Girard, F; Riguet, E; Rouillier, M; Bournique, B; Haddouk, H; Mutel, V; Poli, S

    2014-01-01

    Background and Purpose The GABAB receptor agonist, baclofen, has shown promising effects in patients suffering from pain, post-traumatic stress disorder, alcoholism, overactive bladder and gastroesophageal reflux disease. However, baclofen's short duration of action and side effects limit its wider use. Here we characterized a novel, GABAB receptor positive allosteric modulator (PAM) ADX71943. Experimental Approach In vitro, ADX71943 was assessed for pharmacological activity and selectivity using recombinant and native GABAB receptors. In vivo ADX71943 was assessed in the acetic acid-induced writhing (AAW) test in mice and formalin tests (FTs) in mice and rats. Marble burying (MB) and elevated plus maze (EPM) tests, rotarod, spontaneous locomotor activity (sLMA) and body temperature (BT) tests in mice and rats were used to investigate centrally-mediated effects. Key Results In vitro, in the presence of GABA, ADX71943 increased the potency and efficacy of agonists and showed selectivity at the GABAB receptor. ADX71943 reduced pain-associated behaviours in AAW; an effect blocked by GABAB receptor antagonist CGP63360. ADX71943 reduced pain in the FT in mice and rats, but was inactive in the MB and EPM despite reaching high concentrations in plasma. ADX71943 had no effect on BT, rotarod and sLMA. Conclusions and Implications ADX71943 showed consistent and target-related efficacy in tests of disorders that have a significant peripheral component (acute and chronic pain), while having no effect in those associated with centrally-mediated anxiety-like reactivity and side effects. Thus, ADX71943 is a useful pharmacological tool for delineation of peripherally- versus centrally-mediated effects of GABAB receptor activation. PMID:24923436

  2. Kinetic and optical biosensor study of adrenodoxin mutant AdxS112W displaying an enhanced interaction towards the cholesterol side chain cleavage enzyme (CYP11A1).

    PubMed

    Schiffler, Burkhard; Zöllner, Andy; Bernhardt, Rita

    2011-12-01

    In mammals, steroid hormones are synthesized from cholesterol that is metabolized by the mitochondrial CYP11A1 system leading to pregnenolone. The reduction equivalents for this reaction are provided by NADPH, via a small electron transfer chain, consisting of adrenodoxin reductase (AdR) and adrenodoxin (Adx). The reaction partners are involved in a series of transient interactions to realize the electron transfer from NADPH to CYP11A1. Here, we compared the ionic strength effect on the AdR/Adx and Adx/CYP11A1 interactions for wild-type Adx and mutant AdxS112W. Using surface plasmon resonance measurements, stopped flow kinetic investigations and analyses of the product formation, we were able to obtain new insights into the mechanism of these interactions. The replacement of serine 112 by tryptophan was demonstrated to lead to a dramatically decreased k (off) rate of the Adx/CYP11A1 complex, resulting in a four-fold decreased K (d) value and indicating a much higher stability of the complex involving the mutant. Stopped flow analysis at various ionic strengths and in different mixing modes revealed that the binding of reduced Adx to CYP11A1 seems to display the limiting step for electron transfer to CYP11A1 with pre-reduced AdxS112W being much more efficient than wild-type Adx. Finally, the dramatic increase in pregnenolone formation at higher ionic strength using the mutant demonstrates that the interaction of CYP11A1 with Adx is the rate-limiting step in substrate conversion and that hydrophobic interactions may considerably improve this interaction and the efficiency of product formation. The data are discussed using published structural data of the complexes.

  3. Characterization of Maze Performance in Adrenalectomized Sleep Disrupted Rats: A Comparison of Radial Arm Maze Performance between Adrenalectomized and Sham Adrenalectomized Sleep Disrupted Rats

    DTIC Science & Technology

    2007-01-01

    each of the four final trials. Surgical Protocols 1. Venous jugular catheterization : Following induction an adequate level of anesthesia with IP...sleep disruption performances were compared. In addition, animals were implanted with a venous jugular catheter and sampled over a 36 hour period which...In addition, animals were implanted with a venous jugular catheter, and sampled over a 36 hour period which included 12 hours of baseline, 12

  4. Object/Context-Specific Memory Deficits Associated with Loss of Hippocampal Granule Cells after Adrenalectomy in Rats

    ERIC Educational Resources Information Center

    Spanswick, Simon C.; Sutherland, Robert J.

    2010-01-01

    Chronic adrenalectomy (ADX) causes a gradual and selective loss of granule cells in the dentate gyrus (DG) of the rat. Here, we administered replacement corticosterone to rats beginning 10 wk after ADX. We then tested them in three discrimination tasks based on object novelty, location, or object/context association. Only during testing of the…

  5. Amorphous solid dispersion successfully improved oral exposure of ADX71943 in support of toxicology studies.

    PubMed

    Ayad, Mohamad H; Bonnet, Beatrice; Quinton, Jacques; Leigh, Matthew; Poli, Sonia M

    2013-09-01

    ADX71943 is a potent and selective GABA(b) receptor positive allosteric modulator (PAM) which exhibits poor aqueous solubility at all physiologically relevant pHs. The aim of this study was to identify an adequate formulation to improve the solubility of ADX71943 to achieve a sufficiently high plasma exposure after oral administration to support the toxicology program. Considering the overall physicochemical properties and the low solubility of ADX71943 in a variety of solvents, solid dispersion, and particle size reduction have been successfully chosen as potential strategies to improve its oral bioavailability. Both technologies have proven useful in improving the in vitro dissolution profile and as a result of the solubility enhancement, higher bioavailability was obtained in vivo. As the solid dispersion gave better bioavailability (30-fold compared with the neat active pharmaceutical ingredient (API)), this formulation was selected for the toxicology study. Changing the crystalline form of ADX71943 into amorphous state by preparing a solid dispersion has greatly improved its oral bioavailability and has allowed achieving the required plasma concentration needed in toxicology studies.

  6. REPLACEMENT WITH GABAERGIC STEROID PRECURSORS RESTORES THE ACUTE ETHANOL WITHDRAWAL PROFILE IN ADX/GDX MICE

    PubMed Central

    Kaufman, KR; Tanchuck, MA; Strong, MN; Finn, DA

    2010-01-01

    The neurosteroid allopregnanolone (ALLO) is a progesterone metabolite that is one of a family of neuroactive steroids (NAS) that are potent positive allosteric modulators of γ-aminobutyric acidA (GABAA) receptors. These GABAergic NAS are produced peripherally (in the adrenals and gonads) and centrally in the brain. Peripherally produced NAS modulate some effects of ethanol intoxication (e.g., anxiolytic, antidepressant, and anticonvulsant effects) in rodents. We have found that NAS also may be involved in the rebound neural hyperexcitability following a high ethanol dose. Removal of the adrenals and gonads (ADX/GDX) increased withdrawal severity following 4 g/kg ethanol, as measured by handling-induced convulsions (HICs) in male and female DBA/2J mice. NAS are produced through the metabolism of progesterone (PROG), deoxycorticosterone (DOC), or testosterone, which can be blocked with the administration of finasteride (FIN), a 5α-reductase enzyme inhibitor. The current investigation was undertaken to clarify the step(s) in the biosynthetic NAS pathway that were sufficient to restore the acute ethanol withdrawal profile in ADX/GDX mice to that seen in intact animals. Male and female DBA/2J mice underwent ADX/GDX or SHAM surgery. After recovery, separate groups of animals were administered PROG, DOC, PROG+FIN, DOC+FIN, FIN, ALLO, ganaxalone (a synthetic ALLO derivative), corticosterone, or vehicle. Animals were then administered a 4 g/kg ethanol dose and allowed to undergo withdrawal. HICs were measured for 12 hours and again at 24 hours. The results indicate that replacement with PROG and DOC restored the withdrawal profile in ADX/GDX animals to SHAM levels, and that this effect was blocked with co-administration of FIN. Administration of FIN alone increased the withdrawal profile in both SHAM and ADX/GDX males. These findings indicate that the increase in acute withdrawal severity after ADX/GDX may be due to the loss of GABAergic NAS, providing insight into the

  7. ADX: A high Power Density, Advanced RF-Driven Divertor Test Tokamak for PMI studies

    NASA Astrophysics Data System (ADS)

    Whyte, Dennis; ADX Team

    2015-11-01

    The MIT PSFC and collaborators are proposing an advanced divertor experiment, ADX; a divertor test tokamak dedicated to address critical gaps in plasma-material interactions (PMI) science, and the world fusion research program, on the pathway to FNSF/DEMO. Basic ADX design features are motivated and discussed. In order to assess the widest range of advanced divertor concepts, a large fraction (>50%) of the toroidal field volume is purpose-built with innovative magnetic topology control and flexibility for assessing different surfaces, including liquids. ADX features high B-field (>6 Tesla) and high global power density (P/S ~ 1.5 MW/m2) in order to access the full range of parallel heat flux and divertor plasma pressures foreseen for reactors, while simultaneously assessing the effect of highly dissipative divertors on core plasma/pedestal. Various options for efficiently achieving high field are being assessed including the use of Alcator technology (cryogenic cooled copper) and high-temperature superconductors. The experimental platform would also explore advanced lower hybrid current drive and ion-cyclotron range of frequency actuators located at the high-field side; a location which is predicted to greatly reduce the PMI effects on the launcher while minimally perturbing the core plasma. The synergistic effects of high-field launchers with high total B on current and flow drive can thus be studied in reactor-relevant boundary plasmas.

  8. The pregnane xenobiotic receptor, a prominent liver factor, has actions in the midbrain for neurosteroid synthesis and behavioral/neural plasticity of female rats

    PubMed Central

    Frye, Cheryl A.; Koonce, Carolyn J.; Walf, Alicia A.

    2014-01-01

    A novel factor of interest for growth/plasticity in the brain is pregnane xenobiotic receptor (PXR). PXR is a liver factor known for its role in xenobiotic clearance and cholesterol metabolism. It is expressed in the brain, suggesting a potential role for plasticity, particularly involving cholesterol-based steroids and neurosteroids. Mating induces synthesis of neurosteroids in the midbrain Ventral Tegmental Area (VTA) of female rodents, as well as other “plastic” regions of the brain, including the hippocampus, that may be involved in the consolidation of the mating experience. Reducing PXR in the VTA attenuates mating-induced biosynthesis of the neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP). The 18 kDA translocator protein (TSPO) is one rate-limiting factor for 3α,5α-THP neurosteroidogenesis. The hypothesis tested was that PXR is an upstream factor of TSPO for neurosteroidogenesis of 3α,5α-THP in the VTA for lordosis, independent of peripheral glands. First, proestrous rats were administered a TSPO blocker (PK11195) and/or 3α,5α-THP following infusions of PXR antisense oligonucleotides (AS-ODNs) or vehicle to the VTA. Inhibiting TSPO with PK11195 reduced 3α,5α-THP levels in the midbrain and lordosis, an effect that could be reversed with 3α,5α-THP administration, but not AS-ODN+3α,5α-THP. Second, proestrous, ovariectomized (OVX), or ovariectomized/adrenalectomized (OVX/ADX) rats were infused with a TSPO enhancer (FGIN 1-27) subsequent to AS-ODNs or vehicle to the VTA. PXR AS-ODNs blocked actions of FGIN 1–27 for lordosis and 3α,5α-THP levels among proestrous > OVX > OVX/ADX rats. Thus, PXR may be upstream of TSPO, involved in neurosteroidogenesis of 3α,5α-THP in the brain for plasticity. This novel finding of a liver factor involved in behavioral/neural plasticity substantiates future studies investigating factors known for their prominent actions in the peripheral organs, such as the liver, for modulating brain function and its

  9. Dietary glucose increases plasma insulin and decreases brown adipose tissue thermogenic activity in adrenalectomized ob/ob mice.

    PubMed

    Nei, Y M; Romsos, D R

    1991-09-01

    The purpose of this study was to determine whether consumption of a high glucose diet would increase plasma insulin concentrations and decrease brown adipose tissue metabolism in adrenalectomized ob/ob mice previously fed a high starch diet. Male sham-operated and adrenalectomized ob/ob and lean mice were fed a high starch diet for 12 d, then switched to a high glucose diet for the last 2 or 4 d of the 14- or 16-d feeding trials. Adrenalectomized ob/ob mice consumed 16% more energy and gained 50% more weight without an increase in oxygen consumption when switched from a high starch diet to a high glucose diet. Within 2 d after the switch to the high glucose diet, plasma insulin concentrations increased by 70% without any change in plasma glucose concentrations; brown adipose tissue metabolism, as assessed by GDP binding to brown adipose tissue mitochondria, was decreased by 26% 4 d after the diet switch. Sham-operated ob/ob and lean mice and adrenalectomized lean mice were minimally affected by the switch to the high glucose diet. The increase in plasma insulin concentrations in adrenalectomized ob/ob mice induced by the high glucose diet may contribute to the observed depression in brown adipose tissue metabolism.

  10. ADX: a high field, high power density, advanced divertor and RF tokamak

    NASA Astrophysics Data System (ADS)

    LaBombard, B.; Marmar, E.; Irby, J.; Terry, J. L.; Vieira, R.; Wallace, G.; Whyte, D. G.; Wolfe, S.; Wukitch, S.; Baek, S.; Beck, W.; Bonoli, P.; Brunner, D.; Doody, J.; Ellis, R.; Ernst, D.; Fiore, C.; Freidberg, J. P.; Golfinopoulos, T.; Granetz, R.; Greenwald, M.; Hartwig, Z. S.; Hubbard, A.; Hughes, J. W.; Hutchinson, I. H.; Kessel, C.; Kotschenreuther, M.; Leccacorvi, R.; Lin, Y.; Lipschultz, B.; Mahajan, S.; Minervini, J.; Mumgaard, R.; Nygren, R.; Parker, R.; Poli, F.; Porkolab, M.; Reinke, M. L.; Rice, J.; Rognlien, T.; Rowan, W.; Shiraiwa, S.; Terry, D.; Theiler, C.; Titus, P.; Umansky, M.; Valanju, P.; Walk, J.; White, A.; Wilson, J. R.; Wright, G.; Zweben, S. J.

    2015-05-01

    The MIT Plasma Science and Fusion Center and collaborators are proposing a high-performance Advanced Divertor and RF tokamak eXperiment (ADX)—a tokamak specifically designed to address critical gaps in the world fusion research programme on the pathway to next-step devices: fusion nuclear science facility (FNSF), fusion pilot plant (FPP) and/or demonstration power plant (DEMO). This high-field (⩾6.5 T, 1.5 MA), high power density facility (P/S ˜ 1.5 MW m-2) will test innovative divertor ideas, including an ‘X-point target divertor’ concept, at the required performance parameters—reactor-level boundary plasma pressures, magnetic field strengths and parallel heat flux densities entering into the divertor region—while simultaneously producing high-performance core plasma conditions that are prototypical of a reactor: equilibrated and strongly coupled electrons and ions, regimes with low or no torque, and no fuelling from external heating and current drive systems. Equally important, the experimental platform will test innovative concepts for lower hybrid current drive and ion cyclotron range of frequency actuators with the unprecedented ability to deploy launch structures both on the low-magnetic-field side and the high-magnetic-field side—the latter being a location where energetic plasma-material interactions can be controlled and favourable RF wave physics leads to efficient current drive, current profile control, heating and flow drive. This triple combination—advanced divertors, advanced RF actuators, reactor-prototypical core plasma conditions—will enable ADX to explore enhanced core confinement physics, such as made possible by reversed central shear, using only the types of external drive systems that are considered viable for a fusion power plant. Such an integrated demonstration of high-performance core-divertor operation with steady-state sustainment would pave the way towards an attractive pilot plant, as envisioned in the ARC concept

  11. ADX: a high field, high power density, Advanced Divertor test eXperiment

    NASA Astrophysics Data System (ADS)

    Vieira, R.; Labombard, B.; Marmar, E.; Irby, J.; Shiraiwa, S.; Terry, J.; Wallace, G.; Whyte, D. G.; Wolfe, S.; Wukitch, S.; ADX Team

    2014-10-01

    The MIT PSFC and collaborators are proposing an advanced divertor experiment (ADX) - a tokamak specifically designed to address critical gaps in the world fusion research program on the pathway to FNSF/DEMO. This high field (6.5 tesla, 1.5 MA), high power density (P/S ~ 1.5 MW/m2) facility would utilize Alcator magnet technology to test innovative divertor concepts for next-step DT fusion devices (FNSF, DEMO) at reactor-level boundary plasma pressures and parallel heat flux densities while producing high performance core plasma conditions. The experimental platform would also test advanced lower hybrid current drive (LHCD) and ion-cyclotron range of frequency (ICRF) actuators and wave physics at the plasma densities and magnetic field strengths of a DEMO, with the unique ability to deploy launcher structures both on the low-magnetic-field side and the high-field side - a location where energetic plasma-material interactions can be controlled and wave physics is most favorable for efficient current drive, heating and flow drive. This innovative experiment would perform plasma science and technology R&D necessary to inform the conceptual development and accelerate the readiness-for-deployment of FNSF/DEMO - in a timely manner, on a cost-effective research platform. Supported by DE-FC02-99ER54512.

  12. Effects of Hypergravity and Adrenalectomy on Total Body Bone Mineral Content in Male Rats

    NASA Technical Reports Server (NTRS)

    Girten, Beverly; Moran, Megan; Baer, Lisa; Pruitt, Sean; O'Brien, Cheryl; Arnaud, Sara; Wade, Charles; Bowley, Susan M. (Technical Monitor)

    2000-01-01

    The effects of 14 days of increased gravitational load, and the absence of adrenal stress hormones on total body bone mineral content (BMC) were examined in male Sprague-Dawley rats. Centrifugation at 2 Gs (2G) was used to increase the gravitational load, and bilateral adrenalectomy (ADX) was used to eliminate the production of adrenal stress hormones. Stationary groups at 1 G (1G) and sham operated (SHAM) animals served as controls. Thirty rats (n=6 or 8) made up the four experimental groups (1G SHAM, 1G ADX, 2G SHAM and 2G ADX). BMC was assessed by dual energy X-ray absorptiometry (DXA) and activity was determined through biotelemetry. Body mass and food intake were also measured. Multi-factorial analysis of variance (MANCOVA) and Newman Keuls post hoc tests were used to analyze significant effects (p less than 0.05) for the primary variables. Results indicated that BMC decreased significantly with increased G for both the SHAM and ADX groups. The BMC for the 1 G ADX group was also significantly lower than the 1G SHAM group, however the 2G SHAM and ADX groups were not significantly different. There was a significant decrease in body mass with increased G and there was no ADX effect on body mass. When BMC was normalized for body mass changes, there were no significant group differences. Activity level decreased with body mass, and food intake data showed there was significant hypophagia during the first few days of centrifugation. These results suggest that the decrease in total body BMC seen with hypergravity may be based to a large extent on the differences in body mass induced by the 2 G load.

  13. Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats

    EPA Science Inventory

    Rationale: Air pollutants have been linked to increased incidence of metabolic syndrome however the mechanisms are poorly understood. We have recently shown that ozone exposure induces significant hyperglycemia together with elevated serum leptin and epinephrine in the Wistar Ky...

  14. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

  15. Meta-Modeling of Methylprednisolone Effects on Glucose Regulation in Rats

    PubMed Central

    Fang, Jing; Sukumaran, Siddharth; DuBois, Debra C.; Almon, Richard R.; Jusko, William J.

    2013-01-01

    A retrospective meta-modeling analysis was performed to integrate previously reported data of glucocorticoid (GC) effects on glucose regulation following a single intramuscular dose (50 mg/kg), single intravenous doses (10, 50 mg/kg), and intravenous infusions (0.1, 0.2, 0.3 and 0.4 mg/kg/h) of methylprednisolone (MPL) in normal and adrenalectomized (ADX) male Wistar rats. A mechanistic pharmacodynamic (PD) model was developed based on the receptor/gene/protein-mediated GC effects on glucose regulation. Three major target organs (liver, white adipose tissue and skeletal muscle) together with some selected intermediate controlling factors were designated as important regulators involved in the pathogenesis of GC-induced glucose dysregulation. Assessed were dynamic changes of food intake and systemic factors (plasma glucose, insulin, free fatty acids (FFA) and leptin) and tissue-specific biomarkers (cAMP, phosphoenolpyruvate carboxykinase (PEPCK) mRNA and enzyme activity, leptin mRNA, interleukin 6 receptor type 1 (IL6R1) mRNA and Insulin receptor substrate-1 (IRS-1) mRNA) after acute and chronic dosing with MPL along with the GC receptor (GR) dynamics in each target organ. Upon binding to GR in liver, MPL dosing caused increased glucose production by stimulating hepatic cAMP and PEPCK activity. In adipose tissue, the rise in leptin mRNA and plasma leptin caused reduction of food intake, the exogenous source of glucose input. Down-regulation of IRS-1 mRNA expression in skeletal muscle inhibited the stimulatory effect of insulin on glucose utilization further contributing to hyperglycemia. The nuclear drug-receptor complex served as the driving force for stimulation or inhibition of downstream target gene expression within different tissues. Incorporating information such as receptor dynamics, as well as the gene and protein induction, allowed us to describe the receptor-mediated effects of MPL on glucose regulation in each important tissue. This advanced mechanistic

  16. Consumption of a glucose diet enhances the sensitivity of pancreatic islets from adrenalectomized genetically obese (ob/ob) mice to glucose-induced insulin secretion.

    PubMed

    Mistry, A M; Chen, N G; Lee, Y S; Romsos, D R

    1995-03-01

    Consumption of a glucose diet for 4 d markedly elevates plasma insulin concentrations in adrenalectomized ob/ob mice. The present study examined regulation of insulin secretion from perifused pancreatic islets of female adrenalectomized genetically obese (ob/ob) and lean mice fed a glucose diet for 4 d. These mice were fed a high carbohydrate commercial diet for 21 d, or the high carbohydrate commercial diet for 17 d and a purified high glucose diet for the last 4 d of the 21-d feeding period. Adrenalectomy equalized plasma insulin concentrations, pancreatic islet size, rates of insulin secretion in response to 20 mmol/L glucose and insulin mRNA relative abundance in ob/ob and lean mice fed the commercial diet, but the threshold for glucose-induced insulin secretion determined by a linear glucose gradient remained lower in islets from adrenalectomized ob/ob mice than in those from lean mice (3.8 +/- 0.1 vs. 4.9 +/- 0.2 mmol/L glucose), and addition of acetylcholine to the perifusate lowered the threshold to only 2.0 +/- 0.1 mmol/L glucose in islets from ob/ob mice vs. 3.3 +/- 0.1 mmol/L glucose in lean mice. Switching from the commercial diet to the glucose diet for 4 d increased plasma insulin concentrations -10-fold in islets from adrenalectomized ob/ob mice without affecting islet size, 20 mmol/L glucose-induced insulin secretion or insulin mRNA abundance. Consumption of the glucose diet did, however, markedly lower the threshold for glucose-induced insulin secretion in islets from adrenalectomized ob/ob mice to approximate the abnormally low glucose thresholds in intact ob/ob mice.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effect of pancreatectomy or adrenalectomy on the responses of rats to meal-feeding.

    PubMed

    Kaul, L; Berdanier, C D

    1975-09-01

    The effects of partial pancreatectomy or adrenalectomy and insulin or corticosterone replacement on the responses of rats to meal-feeding were studied. Partial pancreatectomy lowered glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities and resulted in higher blood glucose levels. Partial pancreatectomy did not affect the ability of the animals to adapt to meal-feeding. Insulin supplementation of the pancreatectomized rats restored G6PD and ME activities to those observed in the intact animals and normalized the blood glucose levels in the ad libitum-fed rats. Adrenalectomy decresed the survival of rats subjected to meal-feeding. Eighty percent of the rats died when meal-fed a high glucose diet. Survival was improved when either a 66.5% starch diet or a 40.5% fat diet was substituted for the 66.5% glucose diet. Adrenalectomized meal-fed animals fed 66.5% glucose had higher G6PD and ME activities and higher liver lipid levels than both the adrenalectomized ad libitum-fed and the sham-operated meal-fed rats. Glucocorticoid supplementation lowered G6PD activity in the adrenalectomized meal-fed rats but had no effect on ME activity or liver lipid. Meal-fed adrenalectomized rats had lower liver and serum cholesterol levels than meal-fed intact rats and ad libitum-fed adrenalectomized rats. These cholesterol levels were increased with glucocorticoid supplementation. It was concluded that adaptation to meal-feeding involves an adrenal response to the periodic absence of dietary energy intake, and that the degree of involvement of this response is determined by the composition of the diet.

  18. The Effects of Hypergravity and Adrenalectomy on Bone Mineral Content, Urine Calcium and Body Mass in Rats

    NASA Technical Reports Server (NTRS)

    Lau, A.; Ramirez, J.; Melson, E.; Moran, M.; Baer, L.; Arnaud, S.; Wade, C.; Girten, B.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    The effects of 14 days of increased gravitational load, and the absence of adrenal stress hormones on total body bone mineral content (BMC) were examined in male Sprague-Dawley rats. Centrifugation at 2 Gs (2G) was used to increase the gravitational load, and bilateral adrenalectomy (ADX) was used to eliminate the production of adrenal stress hormones. Stationary groups at 1 G (1G) and sham operated (SHAM) animals served as controls. Thirty rats (n=6 or 8) made up the four experimental groups (1G SHAM, 1G ADX, 2G SHAM and 2G ADX). BMC was assessed by dual energy x-ray absorptiometry (DXA) which was performed to determine the total body bone mineral content, and also through bone ashing of the left femur and the left humerus. Activity was determined through biotelemetry, also body mass and food intake were measured. Multi-factorial analysis of variance (MANCOVA) and Newman Keuls post hoc tests were used to analyze significant effects (p is less than 0.05) for the primary variables. Results from both DXA and the ashed femur indicated that BMC decreased significantly with increased G for both the SHAM and ADX groups. The BMC determined by DXA for the 1G ADX group was also significantly lower than the 1G SHAM group, however the 2G SHAM and 2G ADX groups were not significantly different. However, the bone ashing results showed the femur differed significantly only between the rates of centrifugation and not between the ADX and SHAM. The humerus showed no significant difference between any of the groups. There was a significant decrease in body mass with increased G and there was no ADX effect on body mass. When DXA BMC was normalized for body mass changes, there were no significant group differences. However, with bone ashing, the femur BMC/BW still showed significant difference between rates of centrifugation, with the 2G group being lower. Activity level decreased with body mass, and food intake data showed there was significant hypophagia during the first few days of

  19. Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

    PubMed

    Lamb, Jeffrey P; Engers, Darren W; Niswender, Colleen M; Rodriguez, Alice L; Venable, Daryl F; Conn, P Jeffrey; Lindsley, Craig W

    2011-05-01

    This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.

  20. Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

    PubMed

    Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

    2014-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

  1. Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids.

    PubMed

    Qiu, Guang; Spangler, Edward L; Wan, Ruiqian; Miller, Marshall; Mattson, Mark P; So, Kwok-Fai; de Cabo, Rafael; Zou, Sige; Ingram, Donald K

    2012-10-01

    Glucocorticoids (GC)--corticosterone (CORT) in rodents and cortisol in primates--are stress-induced hormones secreted by adrenal glands that interact with the hypothalamic pituitary axis. High levels of cortisol in humans are observed in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), as well as in diabetes, post-traumatic stress syndrome, and major depression. Experimental models of diabetes in rats and mice have demonstrated that reduction of CORT reduces learning and memory deficits and attenuates loss of neuronal viability and plasticity. In contrast to the negative associations of elevated GC levels, CORT is moderately elevated in dietary restriction (DR) paradigms which are associated with many healthy anti-aging effects including neuroprotection. We demonstrate here in rats that ablating CORT by adrenalectomy (ADX) with replenishment to relatively low levels (30% below that of controls) prior to the onset of a DR regimen (ADX-DR) followed by central administration of the neurotoxin, kainic acid (KA), significantly attenuates learning deficits in a 14-unit T-maze task. The performance of the ADX-DR KA group did not differ from a control group (CON) that did not receive KA and was fed ad libitum (AL). By contrast, the sham-operated DR (SHAM-DR KA) group, SHAM-AL KA group, and ADX-AL KA group demonstrated poorer learning behavior in this task compared to the CON group. Stereological analysis revealed equivalent DR-induced neuroprotection in the SH-DR KA and ADX-DR KA groups, as measured by cell loss in the CA2/CA3 region of the hippocampus, while substantial cell loss was observed in SH-AL and ADX-AL rats. A separate set of experiments was conducted with similar dietary and surgical treatment conditions but without KA administration to examine markers of neurotrophic activity, brain-derived neurotrophic factor (BDNF), transcriptions factors (pCREB), and chaperone proteins (HSP-70). Under these conditions, we noted

  2. Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids

    PubMed Central

    Qui, Guang; Spangler, Edward; Wan, Ruiqian; Miller, Marshall; Mattson, Mark; So, Kwi-fok; de Cabo, Rafael; Zou, Sige; Ingram, Donald

    2012-01-01

    Glucocorticoids (GC)--corticosterone (CORT) in rodents and cortisol in primates--are stress-induced hormones secreted by adrenal glands that interact with the hypothalamic pituitary axis. High levels of cortisol in humans are observed in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), as well as in diabetes, post-traumatic stress syndrome, and major depression. Experimental models of diabetes in rats and mice have demonstrated that reduction of CORT reduces learning and memory deficits and attenuates loss of neuronal viability and plasticity. In contrast to the negative associations of elevated GC levels, CORT is moderately elevated in dietary restriction (DR) paradigms which are associated with many healthy anti-aging effects including neuroprotection. We demonstrate here in rats that ablating CORT by adrenalectomy (ADX) with replenishment to relatively low levels (30% below that of controls) prior to the onset of a DR regimen (ADX-DR) followed by central administration of the neurotoxin, kainic acid (KA), significantly attenuates learning deficits in a 14-unit T-maze task. The performance of the ADX-DR KA group did not differ from a control group (CON) that did not receive KA and was fed ad libitum (AL). By contrast, the sham-operated DR (SHAM-DR KA) group, SHAM-AL KA group, and ADX-AL KA group demonstrated poorer learning behavior in this task compared to the CON group. Stereological analysis revealed equivalent DR-induced neuroprotection in the SH-DR KA and ADX-DR KA groups, as measured by cell loss in the CA2/CA3 region of the hippocampus, while substantial cell loss was observed in SH-AL and ADX-AL rats. A separate set of experiments was conducted with similar dietary and surgical treatment conditions but without KA administration to examine markers of neurotrophic activity, brain-derived neurotrophic factor (BDNF), transcriptions factors (pCREB), and chaperone proteins (HSP-70). Under these conditions, we noted

  3. Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Stamper, Christopher E.; Hennessey, Patrick A.; Hale, Matthew W.; Lukkes, Jodi L.; Donner, Nina C.; Lowe, Kenneth R.; Paul, Evan D.; Spencer, Robert L.; Renner, Kenneth J.; Orchinik, Miles; Lowry, Christopher A.

    2015-01-01

    Previous studies suggest that multiple corticolimbic and hypothalamic structures are involved in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, including the dorsomedial hypothalamus (DMH), but a potential role of the DMH has not been directly tested. To investigate the role of the DMH in glucocorticoid-mediated negative feedback, adult male Sprague Dawley rats were implanted with jugular cannulae and bilateral guide cannulae directed at the DMH, and finally were either adrenalectomized (ADX) or were subjected to sham-ADX. Adrenalectomized rats received CORT replacement in the drinking water (25 µg/ml), which, based on initial studies, restored a rhythm of plasma CORT concentrations in ADX rats that was similar in period and amplitude to the diurnal rhythm of plasma CORT concentrations in sham-ADX rats, but with a significant phase delay. Following recovery from surgery, rats received microinjections of either CORT (10 ng, 0.5 µL, 0.25 µL/min, per side) or vehicle (aCSF containing 0.2% EtOH), bilaterally, directly into the DMH, prior to a 40 min period of restraint stress. In sham-ADX rats, bilateral intra-DMH microinjections of CORT, relative to bilateral intra-DMH microinjections of vehicle, decreased restraint stress-induced elevation of endogenous plasma CORT concentrations 60 minutes after the onset of intra-DMH injections. Intra-DMH CORT decreased the overall area under the curve for plasma CORT concentrations during the intermediate time frame of glucocorticoid negative feedback, from 0.5–2 h following injection. These data are consistent with the hypothesis that the DMH is involved in feedback inhibition of HPA axis activity at the intermediate time frame. PMID:25556980

  4. Body Mass Changes Associated With Hyper-Gravity are Independent of Adrenal Derived Hormones

    NASA Technical Reports Server (NTRS)

    Wade, Charles E.; Moran, Megan M.; Wang, Tommy J.; Baer, Lisa A.; Yuan, Fang; Fung, Cyra K.; Stein, T. Peter; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Exposure to hyper-gravity results in a number of metabolic changes associated with increases in catecholamines and corticosterone. These changes result in a loss of body and fat mass. To assess the role of hormones derived from the adrenal gland in the changes we studied sham operated (SO) and adrenalectomized (ADX) male rats exposed to hyper-gravity of 2 G for 14 days. Control groups at 1 G were also studied. Urinary epinephrine (EPI) and corticosterone (CORT) were reduced in ADX animals. In response to 2 G there was an increase in urinary EPI and CORT in SO rats, while levels were unchanged in ADX animals. Both groups of animals had similar increases in urinary norepinephrine levels. The reductions of body mass gain in response to 2 G were the same in both groups. The decrease in relative fat mass was greater in ADX. Energy intake and expenditure were not different between groups. In response of returning to 1 G for 24 hours and reexposure to hyper-gravity there were no differences between SO and ADX in the changes of food and water intake, body mass or activity. The changes in metabolism with exposure to hyper-gravity do not appear to require hormones derived from the adrenal gland. The increase in lypolysis and alterations body and fat mass appear to be modulated by sympathetically derived norepinehrine.

  5. The CETAC ADX-500 Autodiluter System: A Study of Dilution Performance with the ELAN 6000 ICP-MS and ELAN Software

    USGS Publications Warehouse

    May, T.W.; Wiedmeyer, Ray H.

    1998-01-01

    The CETAC ADX-500 autodiluter system was tested with ELAN?? v 2.1 software and the ELAN 6000 ICP-MS instrument to determine on-line automated dilution performance during analysis of standard solutions containing nine analytes representative of the mass spectral range (mass 9 to mass 238). Two or more dilution schemes were tested for each of 5 test tube designs. Dilution performance was determined by comparison of analyte concentration means of diluted and non-diluted standards. Accurate dilutions resulted with one syringe pump addition of diluent in small diameter round-bottomed (13 mm OD) or conical-tipped (18 mm OD) tubes and one or more syringe pump additions in large diameter (28 mm OD) conical-tipped tubes. Inadequate dilution mixing which produced high analyte concentration means was observed for all dilutions conducted in flat-bottomed tubes, and for dilutions requiring multiple syringe additions of diluent in small diameter round-bottomed and conical tipped tubes. Effective mixing of diluted solutions was found to depend largely upon tube diameter and liquid depth: smaller tube diameters and greater liquid depth resulted in ineffective mixing, whereas greater tube diameter and shallower liquid depth facilitated effective mixing. Two design changes for the autodiluter were suggested that would allow effective mixing to occur using any dilution scheme and tube design.

  6. Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Stamper, Christopher E; Hennessey, Patrick A; Hale, Matthew W; Lukkes, Jodi L; Donner, Nina C; Lowe, Kenneth R; Paul, Evan D; Spencer, Robert L; Renner, Kenneth J; Orchinik, Miles; Lowry, Christopher A

    2015-01-01

    Previous studies suggest that multiple corticolimbic and hypothalamic structures are involved in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, including the dorsomedial hypothalamus (DMH), but a potential role of the DMH has not been directly tested. To investigate the role of the DMH in glucocorticoid-mediated negative feedback, adult male Sprague Dawley rats were implanted with jugular cannulae and bilateral guide cannulae directed at the DMH, and finally were either adrenalectomized (ADX) or were subjected to sham-ADX. ADX rats received corticosterone (CORT) replacement in the drinking water (25 μg/mL), which, based on initial studies, restored a rhythm of plasma CORT concentrations in ADX rats that was similar in period and amplitude to the diurnal rhythm of plasma CORT concentrations in sham-ADX rats, but with a significant phase delay. Following recovery from surgery, rats received microinjections of either CORT (10 ng, 0.5 μL, 0.25 μL/min, per side) or vehicle (aCSF containing 0.2% EtOH), bilaterally, directly into the DMH, prior to a 40-min period of restraint stress. In sham-ADX rats, bilateral intra-DMH microinjections of CORT, relative to bilateral intra-DMH microinjections of vehicle, decreased restraint stress-induced elevation of endogenous plasma CORT concentrations 60 min after the onset of intra-DMH injections. Intra-DMH CORT decreased the overall area under the curve for plasma CORT concentrations during the intermediate time frame of glucocorticoid negative feedback, from 0.5 to 2 h following injection. These data are consistent with the hypothesis that the DMH is involved in feedback inhibition of HPA axis activity at the intermediate time frame.

  7. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

    NASA Technical Reports Server (NTRS)

    Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

    1993-01-01

    Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

  8. Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study

    PubMed Central

    Ruoff, Chad; Swick, Todd J.; Doekel, Robert; Emsellem, Helene A.; Feldman, Neil T.; Rosenberg, Russell; Bream, Gary; Khayrallah, Moise A.; Lu, Yuan; Black, Jed

    2016-01-01

    , Lu Y, Black J. Effect of oral JZP-110 (ADX-N05) on wakefulness and sleepiness in adults with narcolepsy: a phase 2b study. SLEEP 2016;39(7):1379–1387. PMID:27166238

  9. Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion.

    PubMed

    Kim, Kyu-Nam; Kim, Bom-Taeck; Kim, Young-Sang; Lee, Jong-Ho; Jahng, Jeong Won

    2014-05-05

    Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA.

  10. Involvement of the adrenal glands and testis in gap junction formation via testosterone within the male rat anterior pituitary gland.

    PubMed

    Sakuma, Eisuke; Wada, Ikuo; Otsuka, Takanobu; Wakabayashi, Kenjiro; Ito, Kinya; Soji, Tsuyoshi; Herbert, Damon C

    2012-12-01

    We investigated the influence of testicular and adrenal androgens on the presence of gap junctions between folliculo-stellate cells in the anterior pituitary glands of 60-day-old Wistar-Imamichi strain male rats. The animals were separated into six groups: Group A served as the controls and had free access to a normal diet and water, Group B was given a normal diet and 0.9% NaCl for their drinking water as the controls of adrenalectomized groups, Group C was castrated, Group D was adrenalectomized, Group E was both castrated and adrenalectomized, and Group F was also both castrated and adrenalectomized. In addition, the animals of Group F were administered a dose of testosterone that is known to produce high physiological levels of the hormones in plasma. Five rats from each group were sacrificed 1, 2, 3, 4, 5, 6, and 7 days after their respective operation, and the anterior pituitary glands were removed and prepared for observation by transmission electron microscopy. We quantified the number of follicles and gap junctions and calculated the rate of occurrence as the ratio of the number of gap junctions existing between folliculo-stellate cells per intersected follicle profile. Simultaneous removal of adrenal glands with castration resulted in a significantly decrease in the number of gap junctions, whereas the administration of testosterone to these rats compensated for this change. These observations indicate that the preservation of gap junctions between folliculo-stellate cells is mainly dependent on androgens from both the testes and adrenal glands in adult male rats.

  11. Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

    PubMed

    Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

    2011-07-01

    Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation.

  12. Autoradiographic analysis of hepatocytes in mirex-induced adaptive liver growth

    SciTech Connect

    Wilson, D.; Yarbrough, J.D. )

    1988-07-01

    The relationships between ({sup 3}H)thymidine incorporation into hepatocyte nuclei, cell enlargement, and mitotic index were studied in intact (INT) and adrenalectomized (ADX) mirex-dosed rats. In INT mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear labeling of mononuclear hepatocyes with peaks at 48 and 66 h postmirex dose, a peak in mitotic activity 66 h postmirex dose, and a significant increase in binuclear hepatocyte size 48 h postmirex dose. In ADX mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear labeling mononuclear hepatocytes with peaks at 24 and 48 h postmirex dose, a peak in mitotic activity 60 h postmirex dose, and a marginal increase in binuclear hepatocyte size 48 h postmirex dose. Corticosterone supplements to ADX mirex-dosed rats significantly reduced nuclear labeling of the mononuclear hepatocytes and increased the size of binuclear hepatocytes to that observed in INT mirex-dosed rats. This study demonstrates that adaptive liver growth consists of a hyperplastic response that involves mononuclear hepatocytes and a hypertrophic response that involves binuclear hepatocytes. Both responses appear to be modulated by corticosterone.

  13. Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry.

    PubMed

    Ozawa, Hitoshi; Han, Fang; Kawata, Mitsuhiro

    2004-12-01

    Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and

  14. Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

    Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

  15. Influence of steroid-hormone-receptor-protein complexes on initiation of ribonucleic acid synthesis in liver nuclei isolated from rats of various ages.

    PubMed Central

    Miller, J K; Bolla, R

    1981-01-01

    The effect of age on the induction of the initiation of RNA synthesis was investigated in liver nuclei isolated from adrenalectomized rats of various ages after binding of a dexamethasone-receptor-protein complex. Binding of this complex to nuclear chromatin resulted in increased initiation of nuclear RNA synthesis at all ages; however, an age-associated decline in the extent of this induction was observed. This suggests an age-related decrease of total rat liver nuclear RNA synthesis with a decreased response to glucocorticoid hormones. PMID:6171268

  16. Localization and hormonal control of serine dehydratase during metabolic acidosis differ markedly from those of phosphoenolpyruvate carboxykinase in rat kidney.

    PubMed

    Masuda, Tohru; Ogawa, Hirofumi; Matsushima, Takako; Kawamata, Seiichi; Sasahara, Masakiyo; Kuroda, Kazunari; Suzuki, Yasuhiro; Takata, Yoshimi; Yamazaki, Mitsuaki; Takusagawa, Fusao; Pitot, Henry C

    2003-08-01

    Serine dehydratase (SDH) is abundant in the rat liver but scarce in the kidney. When administrated with dexamethasone, the renal SDH activity was augmented 20-fold, whereas the hepatic SDH activity was affected little. In situ hybridization and immunohistochemistry revealed that SDH was localized to the proximal straight tubule of the nephron. To address the role of this hormone, rats were made acidotic by gavage of NH(4)Cl. Twenty-two hours later, the SDH activity was increased three-fold along with a six-fold increment in the phosphoenolpyruvate carboxykinase (PEPCK) activity, a rate-limiting enzyme of gluconeogenesis. PEPCK, which is localized to the proximal tubules under the normal condition, spreads throughout the entire cortex to the outer medullary rays by acidosis, whereas SDH does not change regardless of treatment with dexamethasone or NH(4)Cl. When NH(4)Cl was given to adrenalectomized rats, in contrast to the SDH activity no longer increasing, the PEPCK activity responded to acidosis to the same extent as in the intact rats. A simultaneous administration of dexamethasone and NH(4)Cl into the adrenalectomized rats fully restored the SDH activity, demonstrating that the rise in the SDH activity during acidosis is primarily controlled by glucocorticoids. The present findings clearly indicate that the localization of SDH and its hormonal regulation during acidosis are strikingly different from those of PEPCK.

  17. Adrenal-dependent diurnal modulation of conditioned fear extinction learning.

    PubMed

    Woodruff, Elizabeth R; Greenwood, Benjamin N; Chun, Lauren E; Fardi, Sara; Hinds, Laura R; Spencer, Robert L

    2015-06-01

    Post traumatic stress disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12h light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats' active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD.

  18. Mechanism of potassium depletion during chronic metabolic acidosis in the rat

    SciTech Connect

    Scandling, J.D.; Ornt, D.B.

    1987-01-01

    Pair-fed rats on a normal K diet were given either 1.5% NH/sub 4/Cl or water for 4 days. The acid-fed animals developed metabolic acidosis, negative K balance, and K depletion. Urinary Na excretion and urinary flow were not different between the groups beyond the first day. After the 4 days, isolated kidneys from animals in each of these groups were perfused at normal pH and bicarbonate concentrations. Urinary K excretion was similar between the groups despite the potassium depletion in the acid-fed animals. In contrast, isolated kidneys from animals with comparable K depletion induced by dietary K restriction readily conserved K. Sodium excretion and urinary flow were similar among the three groups of isolated kidneys. Plasma aldosterone concentrations were greater in the acid-fed rats after the 4 days of NH/sub 4/Cl ingestion than in the control animals. Adrenalectomized rats were treated with either normal (4 ..mu..g/day) or high (22 ..mu..g/day) aldosterone replacement while ingesting NH/sub 4/Cl for 4 days. Only in the presence of high aldosterone replacement did the acid-fed adrenalectomized animals develop K depletion. The authors conclude that chronic metabolic acidosis stimulates aldosterone secretion, and that aldosterone maintains the inappropriately high urinary potassium excretion and K depletion seen in this acid-base disorder.

  19. Effects of xenogeneic, allogeneic and isogeneic thymus grafts on lymphocyte populations in peripheral lymphoid organs of the nude rat.

    PubMed

    Hougen, H P; Klausen, B; Stenvang, J P; Kraemmer, J; Rygaard, J

    1987-04-01

    In order to gain information about the effect of xenografted, allografted and isografted thymic tissue on peripheral lymphoid organs of immune-deficient rats, athymic nude LEW rats of ninth backcross-intercross were grafted with fetal calf and neonatal BDIX and LEW thymus. Adrenalectomy was also performed in some animals in order to obtain a possible enhancement of the immunological reconstitution. Both groups of isogeneic-thymus-grafted animals had more T helper cells than the nude controls. Furthermore, they had more densely populated paracortical areas in the inguinal lymph nodes and higher lymphocyte counts in the thoracic duct lymph. Finally, the inguinal lymph nodes contained germinal centres. Xenogeneic and allogeneic thymus transplants did not induce constant changes in the parameters observed compared with the untreated nudes. No clear difference was observed between the adrenalectomized and non-adrenalectomized thymic-isografted animals. We therefore conclude that of all the experimental animals examined the isografted nude rats show by far the best response and that adrenalectomy seems unnecessary for the success of neonatal isogeneic thymus grafts. We also conclude that the isogeneic-thymus-grafted nude rat is a suitable tool for immunological reconstitution studies.

  20. Adrenal-dependent diurnal modulation of conditioned fear extinction learning

    PubMed Central

    Woodruff, Elizabeth R.; Greenwood, Benjamin N.; Chun, Lauren E.; Fardi, Sara; Hinds, Laura R.; Spencer, Robert L.

    2015-01-01

    Post Traumatic Stress Disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12 hr light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats’ active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD. PMID:25746455

  1. Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones.

    PubMed

    Mueller, Anka D; Pollock, Michael S; Lieblich, Stephanie E; Epp, Jonathan R; Galea, Liisa A M; Mistlberger, Ralph E

    2008-05-01

    Sleep deprivation (SD) can suppress cell proliferation in the hippocampal dentate gyrus of adult male rodents, suggesting that sleep may contribute to hippocampal functions by promoting neurogenesis. However, suppression of cell proliferation in rats by the platform-over-water SD method has been attributed to elevated corticosterone (Cort), a potent inhibitor of cell proliferation and nonspecific correlate of this procedure. We report here results that do not support this conclusion. Intact and adrenalectomized (ADX) male rats were subjected to a 96-h SD using multiple- and single-platform methods. New cells were identified by immunoreactivity for 5-bromo-2'-deoxyuridine (BrdU) or Ki67 and new neurons by immunoreactivity for BrdU and doublecortin. EEG recordings confirmed a 95% deprivation of rapid eye movement (REM) sleep and a 40% decrease of non-REM sleep. Cell proliferation in the dentate gyrus was suppressed by up to 50% in sleep-deprived rats relative to apparatus control or home cage control rats. This effect was also observed in ADX rats receiving continuous low-dose Cort replacement via subcutaneous minipumps but not in ADX rats receiving Cort replacement via drinking water. In these latter rats, Cort intake via water was reduced by 60% during SD; upregulation of cell proliferation by reduced Cort intake may obscure inhibitory effects of sleep loss on cell proliferation. SD had no effect on the percentage of new cells expressing a neuronal phenotype. These results demonstrate that the Cort replacement method is critical for detecting an effect of SD on cell proliferation and support a significant role for sleep in adult neurogenesis.

  2. The glucocorticoid system is required for the voluntary exercise-induced enhancement of learning and memory in rats.

    PubMed

    Hajisoltani, Razieh; Rashidy-Pour, Ali; Vafaei, Abbas A; Ghaderdoost, Behshid; Bandegi, Ahmad Reza; Motamedi, Fereshteh

    2011-05-16

    Although it is well established that voluntary exercise can improve cognitive functions, the underlying mechanisms are largely unknown. Glucocorticoids play an important role in learning and memory functions. This study addressed whether the glucocorticoid system would play a role in the exercise-induced enhancement of learning and memory. Intact rats or those that were either adrenalectomized or daily given the corticosterone-synthesis inhibitor metyrapone were allowed to freely exercise in a running wheel for 10 days. Control animals were kept sedentary for this period. After this period, they were trained and tested on a water-maze spatial task using three-trial per day for 5 consecutive days, succeeded by a probe trial two days later. Exercise increased plasma corticosterone levels, as assessed after this 10-day period. Both adrenalectomy and metyrapone slightly reduced running-wheel activity. Adrenalectomy reduced the plasma corticosterone levels to almost zero whereas metyrapone selectively blocked the exercise-induced increase in corticosterone levels. Exercise significantly improved performance during both training and retention of the water-maze task whereas this effect was absent in both adrenalectomized and metyrapone-treated rats. These findings indicate that the glucocorticoid system play a crucial role in the beneficial effects of voluntary exercise on cognitive functions in rats.

  3. Effects of stress, circadian rhythms, and dietary sodium on brain cell-nuclear uptake of aldosterone and corticosterone

    SciTech Connect

    Yongue, B.G.

    1985-01-01

    The binding of the adrenal steroid hormones aldosterone (ALD) and corticosterone (CORT) in brain cell-nuclei has been implicated as a necessary step in the behavioral and physiological actions of these hormones. In vivo uptake of radioactively labeled ALD and CORT in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both of these hormones in limbic brain regions (such as hippocampus, septum and amygdala). Research using sub-cellular fractionation and radioimmunoassay (RIA), has confirmed both the presence of endogenously secreted CORT in cell-nuclei and its limbic localization in the brains of adrenal-intact rats. In this study, environmental and dietary factors were manipulated to induce variation in serum ALD and CORT. A series of experiments employing sub-cellular fractionation and RIA were performed, which reveal that: (1) endogenously secreted ALD and CORT, are concentrated by cell-nuclei of the brain in adrenal-intact rats, (2) the majority of the corticosteroids measured in ethanol extracts of brain cell-nuclei are associated with receptor molecules, and (3) the regional distribution of endogenously secreted ALD differs markedly from the predominantly limbic pattern predicted from in vivo uptake of labeled ALD in ADX rats. Instead, brain cell-nuclear ALD is heavily concentrated in the hypothalamus, which supports the hypothesized relationship between the interaction of ALD and angiotensin in the brain and the behavioral regulation of fluid/electrolyte balance.

  4. Expression of glucocorticoid receptor and coactivators in ependymal cells of male rats.

    PubMed

    Iwata, Kinuyo; Ozawa, Hitoshi

    2014-08-29

    Glucocorticoid receptor (GR) is a ligand-activated nuclear receptor which is widely distributed in the brain. Many types of neurons and glial cells are known to express GR, but the expression of GR in ependymal cells has yet to be identified. The present study therefore was undertaken to determine whether ependymal cells express GR and coactivators of GR, such as steroid receptor coactivator 1 (SRC-1) and p300. GR immunoreactivity was found in cells immunopositive to vimentin, a marker of ependymal cells, around the third ventricle (3V), the lateral ventricle (LV), the cerebral aqueduct and the fourth ventricle (4V), whereas the expression of GR in vimentin-immunoreactive (ir) cells was significantly reduced by adrenalectomy (ADX) in male rats. Vimentin-ir cells also expressed both SRC-1 and p300 at around 3V, LV, the cerebral aqueduct and 4V. ADX had no effect on the expression of SRC-1 or p300 in vimentin-ir cells. These results suggest that glucocorticoid may exert effects on ependymal cells through binding to GR followed by association with SRC-1 and p300 to maintain brain environment under stressful conditions.

  5. Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.

    PubMed

    Frías-Domínguez, Carmen; Garduño, Julieta; Hernández, Salvador; Drucker-Colin, René; Mihailescu, Stefan

    2013-09-01

    Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of

  6. Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones.

    PubMed

    Fleshner, Monika; Campisi, Jay; Amiri, Leila; Diamond, David M

    2004-10-01

    Heat-shock proteins (Hsp) play an important role in stress physiology. Exposure to a variety of stressors will induce intracellular Hsp72, and this induction is believed to be beneficial for cell survival. In contrast, Hsp72 released during stress (extracellular Hsp72; eHsp72) activates pro-inflammatory responses. Clearly, physical stressors such as heat, cold, H(2)O(2), intense exercise and tail shock will induce both intra- and extracellular Hsp72. The current study tested whether a psychological stressor, cat exposure, would also trigger this response. In addition, the potential role of adrenal hormones in the Hsp72 response was examined. Adult, male Sprague Dawley rats were either adrenalectomized (ADX) or sham operated. Ten days post-recovery, rats were exposed to either a cat with no physical contact or control procedures (n = 5-6/group) for 2 h. Levels of intracellular Hsp72 were measured in the brain (frontal cortex, hippocampus, hypothalamus, dorsal vagal complex) and pituitary (ELISA). Levels of eHsp72 (ELISA) and corticosterone (RIA) were measured from serum obtained at the end of the 2-h stress period. Rats that were exposed to a cat had elevated intracellular Hsp72 in hypothalamus and dorsal vagal complex, and elevated eHsp72 and corticosterone in serum. Both the intra- and extracellular Hsp72 responses were blocked or attenuated by ADX. This study demonstrates that cat exposure can stimulate the Hsp72 response and that adrenal hormones contribute to this response.

  7. RNA polymerase activities associated with mirex-induced adaptive liver growth

    SciTech Connect

    Yarbrough, J.D.; Grimley, J.M.

    1986-03-01

    Chromatin-bound poly(d(A-T)) dependent RNA polymerase II and I plus III activities were measured in intact and adrenalectomized mirex-dosed rats. In intact mirex-dosed rats there was a 92% decrease in hepatic chromatin-bound RNA polymerase II activity 36 hrs post mirex dose. Chromatin-bound RNA polymerase I plus II activity increased with time post mirex dose: 70% at 12 hrs; 99% at 36 hrs, and 179% at 48 hrs. Adrenalectomy (ADX) reduced chromatin-bound RNA polymerase II activity by 45%. Contrary to the intact response, there was no change in chromatin-bound polymerase II activity in ADX mirex dosed rats. There was a marked change in the composition of total chromatin-bound RNA polymerases with time following the mirex dose. By 36 hrs post mirex dose, chromatin-bound RNA polymerase I plus III was 98% of the total. The sequence of events that occur in mirex-induced adaptive liver growth include: a 70-80% increase in relative liver weight at 72 hrs; a 48 hr peak in (/sup 3/H)thymidine incorporation into DNA; a significant reduction in chromatin-bound RNA polymerase II activity at 37 hrs; and significant increases in polymerase I plus III activity (from 24-48 hrs post mirex dose).

  8. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    PubMed

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  9. Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus.

    PubMed

    Chao, H M; McEwen, B S

    1994-10-01

    The genes encoding brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and basic fibroblast growth factor (bFGF) are all expressed in the adult rat hippocampus. The colocalization of the these factors with the receptors to which they bind, namely trkB, trkC and the bFGF receptor, respectively, suggests that in the hippocampus they may exert their putative protective and trophic effects through an autocrine mechanism. The morphology and survival of hippocampal neurons are also affected by glucocorticoids, which can act as transcriptional activators of gene expression. In this study we have used in situ hybridization to investigate the adrenal steroid regulation of the mRNAs encoding the neurotrophic factors BDNF, NT-3, and bFGF, their respective receptors, and the growth-associated protein GAP-43. After 7 days of adrenalectomy (ADX), there was an increase in the level of GAP-43 mRNA expression in the CA1 and CA3 pyramidal cell layers of the hippocampus, that was prevented by corticosterone replacement to the ADX animals. In the CA2 subregion, adrenalectomy resulted in a decrease in bFGF mRNA expression, that was reversed by steroid treatment. There was evidence for glucocorticoid modulation of the BDNF and NT-3 mRNAs in pyramidal cell layers and in the dentate gyrus, but not of the mRNAs encoding the trkB, trk C or bFGF receptors.

  10. Immunobiological changes of in vivo glucocorticoid depleted male Swiss albino rats.

    PubMed

    Bishayi, Biswadev; Ghosh, Soumya

    2007-01-01

    Whether endogenous deficiency of adrenal corticosteroid by unilateral adrenalectomy leads to any modulation of macrophage response is not clear and needs investigation in detail. We performed unilateral adrenalectomy on male Swiss albino rats. Fractions of splenic macrophages were isolated and their functional activities were determined. To test the effect of adrenal hormone insufficiency (after unilateral adrenalectomy) on the cell mediated and humoral immune response, sheep red blood cells were injected, then the delayed type hypersensitivity (DTH) response and the number of antibody secreting plasma cells were determined. Studies reported herein indicate that in vivo glucocorticoid (GC) insufficiency due to unilateral adrenalectomy decreases chemotactic migration, myeloperoxidase enzyme release, and lysozyme release from rat splenic macrophages that were also related to the induction of cell mediated and humoral immune responses. The maximum number of plaque was obtained from control cells isolated from spleen after 10 days from the control rats, whereas the number of plaque was decreased in spleens isolated 20 days after unilateral adrenalectomy. Our study also showed time dependent decrease in foot pad swelling in the unilaterally adrenalectomized rats where endogenous GC was reduced with respect to control indicating reduced DTH response in case of GC insufficiency. We found slower clearance of bacterial burden from the blood and spleen isolated from unilaterally adrenalectomized rats with respect to control. Thus on one hand partially GC insufficient animals show altered macrophage response and on the other hand it heightens the persistence (in vivo) of Staphylococus aureus. The study may be helpful in understanding that adrenal corticosteroid insufficiency due to adrenalectomy interferes with immune functions, which may also support the hypothesis that endogenous GC plays a role in regulating immune response.

  11. Regulation of renal Na -K-ATPase in the rat: role of increased potassium transport

    SciTech Connect

    Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

    1986-08-01

    The purpose of this study was to characterize the alterations in collecting tubule Na -K -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na -K -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na -K -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na -K -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na -K -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na -K -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading.

  12. Role of RT6{sup +} T lymphocytes in mercury-induced renal autoimmunity: Experimental manipulations of {open_quotes}susceptible{close_quotes} and {open_quotes}resistant{close_quotes} rats

    SciTech Connect

    Kosuda, L.L.; Hosseinzadeh, H.; Bigazzi, P.E.; Greiner, D.L. |

    1994-12-31

    Brown Norway (BN) rats, {open_quotes}susceptible{close_quotes} to the autoimmune effects of mercury, experience a decrease of peripheral RT6.2{sup +} T lymphocytes after the injection of relatively low doses of mercury chloride. This change coincides with the appearance of circulating autoantibodies to renal antigens (e.g., laminin). Lewis (LEW) rats, {open_quotes}resistant{close_quotes} to the autoimmune effects of mercury, do not show significant decreases of RT6{sup +} T cells. It is possible that BN rats are particularly sensitive to stress induced by mercury and that secretion of adrenocortical hormones decreases levels of RT6{sup +} T cells in this rat strain. Alternatively, mercury may induce a graft-versus-host-like syndrome in BN rats, resulting in higher levels of corticosteroids capable of affecting RT6{sup +} lymphocytes. To eliminate the possible influence of adrenocortical hormones, we have adrenalectomized BN rats prior to administration of mercury. Autoimmune responses to renal antigens were not affected by this experimental manipulation. Similarly, adrenalectomized rats exposed to mercury showed a significant decrease of RT6{sup +} T lymphocytes in cervical lymph nodes. Overall, these observations do not support the hypothesis that increases in adrenocortical hormones play a major role in mercury-induced changes of RT6{sup +} T cells. We have also explored whether experimental depletion of RT6{sup +} T lymphocytes would result in autoimmunity. Gamma irradiation of BN rats led to a decrease of RT6{sup +} T splenocytes, but by itself (i.e., without exposure to mercury) did not cause autoimmune responses to renal antigens. In addition, gamma-irradiated BN rats treated with mercury had autoimmune responses similar to those observed in mercury-treated nonirradiated controls. 38 refs., 4 tabs.

  13. Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

    SciTech Connect

    Bagby, G.J.; Corll, C.B.; Martinez, R.R.

    1987-07-01

    Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.

  14. Role of glucocorticoids in the response of rat leg muscles to reduced activity

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Tischler, Marc E.

    1986-01-01

    Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

  15. Sympathetic neural control of indoleamine metabolism in the rat pineal gland

    NASA Technical Reports Server (NTRS)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

    1975-01-01

    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  16. Aldosterone-reversible decrease in the density of renal peripheral benzodiazepine receptors in the rat after adrenalectomy

    SciTech Connect

    Basile, A.S.; Ostrowski, N.L.; Skolnick, P.

    1987-03-01

    A statistically significant decrease in the density of peripheral benzodiazepine receptors was observed in renal membranes of rats beginning 2 weeks after adrenalectomy when compared with sham-operated controls. This decrease in peripheral benzodiazepine receptor density was manifest as a decrease in the maximum binding of two ligands, (/sup 3/H)Ro 5-4864 and (/sup 3/H)PK 11195, without accompanying changes in their Kd for this site. Similar changes were not seen in another aldosterone-sensitive organ, the submandibular salivary gland. The decrease in peripheral benzodiazepine receptor density observed in adrenalectomized rat renal membranes was restored to control levels after 1 week of aldosterone administration using a dose (12.5 micrograms/kg/day) that had no effect on peripheral benzodiazepine receptor density in sham-operated animals. In contrast, dexamethasone administration (50 micrograms/kg/day, 1 week) had no effect on renal peripheral benzodiazepine receptor density when administered to either adrenalectomized or sham-operated rats. Further, adrenal demedullation had no effect on renal peripheral benzodiazepine receptor density or affinity. The decrease in peripheral benzodiazepine receptor density was localized to the renal cortex and the outer stripe of the medulla by gross dissection of renal slices and renal tissue section autoradiography. The specific effect of adrenalectomy on renal peripheral benzodiazepine receptor density, the lack of direct effect of aldosterone on (/sup 3/H) Ro 5-4864 binding and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggest that these changes may reflect an adaptation of the renal nephron (possibly the distal convoluted tubule, intermediate tubule and/or the collecting duct) to the loss of mineralocorticoid hormones.

  17. Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids

    PubMed Central

    1989-01-01

    Lewis rats with experimental allergic encephalomyelitis (EAE), induced either by the subcutaneous injection of guinea pig myelin basic protein (MBP) or by the adoptive transfer of MBP-primed spleen cells, suffer from a single episode of paralysis from which they recover spontaneously. Animals developing EAE were found to have greatly elevated levels of corticosterone in the blood. This endogenous increase in steroid production was accompanied by lymphopenia and depressed delayed-type hypersensitivity responses to OVA, indicating that rats with EAE are immunosuppressed in an antigen-nonspecific fashion. Adrenalectomized rats given subcutaneous implants of corticosterone to maintain basal steroid levels invariably died when EAE was induced. However, if the steroid replacement therapy was adjusted to mimic the hormone levels that were observed in intact rats developing EAE, then the disease followed a nonfatal course closely resembling that seen in the nonadrenalectomized controls. Replacement therapy that achieved serum corticosterone levels slightly higher than those found in intact rats with EAE virtually suppressed the disease completely. It is concluded that endogenous corticosterone release in rats with EAE plays an essential role in the spontaneous recovery that is observed in this condition. However, the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated corticosterone levels. This finding is discussed in the light of other data that suggest that unlike the spontaneous recovery, the refractory state has an immunological basis rather than an endocrinological basis. PMID:2783450

  18. Control of oxidative stress in microcirculation of spontaneously hypertensive rats.

    PubMed

    DeLano, F A; Balete, R; Schmid-Schönbein, G W

    2005-02-01

    One mechanism for organ damage in individuals with arterial hypertension may be due to oxygen free radical production. This study was designed to localize free radicals in a microvascular network of mature spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Because glucocorticoids play a role in pressure elevation of SHRs, we investigated their role in microvascular free radical formation. Oxygen radical production in mesentery was detected by tetranitroblue tetrazolium reduction to formazan aided by digital light-absorption measurements. Formazan deposits were observed in the endothelial cells and lumens of all microvessels and in lymphatic endothelia but were fewer in tissue parenchyma. The formazan distribution in younger (14-16 wk old) WKY rats and SHRs was heterogeneous with low values in capillaries and small arterioles/venules (<30 microm) but enhanced deposits in larger venules. Adrenalectomy served to reduce the formazan density in SHRs to the level of WKY rats, whereas dexamethasone supplementation of the adrenalectomized rats caused elevation in the larger venules of SHRs. In older (40 wk old) SHRs, formazan levels were elevated in all hierarchies of microvessels. After pressure reduction was employed with chronic hydralazine treatment, the formazan deposits were reduced in all locations of the microcirculation in both WKY rats and SHRs. Elevated formazan deposits were also found in lymphatic endothelium. These results suggest that oxygen free radical production is elevated in both high- and low-pressure regions of SHR microcirculation via a process that is controlled by glucocorticoids. Older SHRs have higher formazan levels than younger SHRs in all microvessels. Chronic hydralazine treatment, which serves to reduce arterial blood pressure, attenuates tetranitroblue tetrazolium reduction in WKY rats and SHRs even in venules of the microcirculation, which has no micropressure elevation. Free radical production may be a more

  19. [Effect of fetal adrenal hormones on the reactivity of the hypothalamo-hypophyseal-adrenocortical system in the adult rat].

    PubMed

    Dygalo, N N; Naumenko, E V

    1984-01-01

    It was found in the experiments on adult males, descendants of the intact or adrenalectomized (prior to mating) female rats which were injected during the pregnancy with adrenaline, hydrocortisone or saline solution, that the reaction of their hypophysial-adrenocortical system to emotional stress or injection of noradrenaline into brain were inversely proportional to the content of corticosteroids, rather than of adrenaline, in the blood of their mothers during the pregnancy. On the other hand, the coupled changes of the levels of corticosteroids and adrenaline in the blood of pregnant mothers only was accompanied by the marked decrease in the sensitivity of brain cholinergic mechanisms in descendants. Hence, the changes of the levels of both adrenaline and corticosterids in the blood of pregnant females modify the reactivity of hypophysial-adrenocortical system of adult descendants, apparently, via the development of brain neurochemical mechanisms in the foetuses. But the role of these hormones is different.

  20. Adrenalectomy induces a decrease in the light scatter properties and amylase content of isolated zymogen granules from rat pancreas as analyzed by flow cytometry.

    PubMed

    Garcia-Montero, A C; De Dios, I; Rodriguez, A I; Orfao, A; Manso, M A

    1995-12-01

    The effect of glucocorticoid deprivation induced in male rats by adrenalectomy on the pancreatic zymogen granules was studied. Zymogen granules were purified from control, sham-operated and adrenalectomized animals studied 1, 3 and 7 days after surgery. The zymogen granules were characterized by flow cytometry, and in each granule the size (based on the forward or low angle light scatter (FSC) parameter), membrane complexity (based on side or 90 degrees light scatter (SSC) parameter) and amylase content were evaluated. Amylase content/DNA ratio in pancreatic homogenates was also analyzed. The zymogen granules of the control rats were found to be distributed in two populations: a major one-R1 (95.45 +/- 1.21%)-containing zymogen granules with a smaller mean size and complexity, and a minor population-R2 (4.45 +/- 0.24%)-the granules of which had a mean size which was larger and more complex. At day +1 after adrenalectomy the zymogen granules were significantly (P < 0.05) smaller than those of control animals. The R2 zymogen granules were similar to those from R1 as regards their size, but were more complex, suggesting that the immediate effect of glucocorticoid deprivation is to induce a depletion of the larger granules presumably belonging to the R2 population. The amount of amylase per granule did not vary at day +1 after adrenalectomy, although the amylase content/size ratio per granule was significantly (P < 0.001) increased. This mechanism could be explained in terms of the existence of a bypass defined in the adrenalectomized animals between the granular content and cytosolic enzymes. Prolongation of the adrenalectomy period to 3 and 7 days resulted in a progressive increase in zymogen granule size and complexity, both parameters showing similar characteristics to those of the controls at day +7 after adrenalectomy. However, the percentage of zymogen granules within the R1 and R2 populations was clearly different from that of controls since the R2 population

  1. Tianeptine: an antidepressant with memory-protective properties.

    PubMed

    Zoladz, Phillip R; Park, Collin R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

    2008-12-01

    The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine's prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression.

  2. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-06-17

    Effects of Immunotherapy; Metastatic/Recurrent Cervical Cancer; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  3. Effects and underlying mechanisms of human opiorphin on cardiovascular activity in anesthetized rats.

    PubMed

    Tian, Xiao-zhu; Chen, Yong; Bai, Lu; Luo, Pan; Du, Xue-jing; Chen, Qiang; Tian, Xin-min

    2015-02-15

    The present study was performed to investigate the peripheral cardiovascular effects of opiorphin in anesthetized rats. Intravenous (i.v.) injection of opiorphin (50-500nmol/kg) caused marked dose-dependent increase in blood pressure and heart rate. The pressor and tachycardic responses induced by opiorphin (300nmol/kg, i.v.) were significantly decreased by pretreatment with angiotensin-converting enzyme inhibitor captopril or angiotensin II type 1 (AT1) receptor antagonist valsartan, which suggested that endogenous angiotensin may be involved in the response to opiorphin. Pretreatment with α-adrenoreceptor antagonist phentolamine and β-adrenoceptor antagonist propranolol respectively attenuated the pressor response induced by opiorphin. Propranolol, but not phentolamine, inhibited the tachycardic response. Moreover, reserpine blocked both responses to opiorphin. These findings indicated that the effects of opiorphin to increase blood pressure and heart rate might be due to the stimulation of sympathetic ganglia. Additionally, studies with bilaterally adrenalectomized rats showed that adrenal medulla may be involved in the cardiovascular regulation of opiorphin. In addition, pretreatment with nonselective opioid receptor antagonist naloxone did not modify the cardiovascular responses to opiorphin, suggesting that the effects of opiorphin were not related to the opioid system. Furthermore, radioimmunoassay (RIA) showed that opiorphin significantly increased endogenous levels of angiotensin II and angiotensin III. In summary, all the results indicate that the cardiovascular effects induced by opiorphin are mediated through the renin-angiotensin system (RAS), the sympathetic ganglia and adrenal medulla, but not the opioid system.

  4. Role of TrkB expression in rat adrenal gland during acute immobilization stress

    PubMed Central

    Kondo, Yusuke; To, Masahiro; Saruta, Juri; Hayashi, Takashi; Sugiyama, Hiroki; Tsukinoki, Keiichi

    2013-01-01

    Expression of tyrosine receptor kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), is markedly elevated in the adrenal medulla during immobilization stress. Catecholamine release was confirmed in vitro by stimulating chromaffin cells with recombinant BDNF. We investigated the role of TrkB and the localization of BDNF in the adrenal gland during immobilization stress for 60 min. Blood catecholamine levels increased after stimulation with TrkB expressed in the adrenal medulla during 60-min stress; however, blood catecholamine levels did not increase in adrenalectomized rats. Furthermore, expression of BDNF mRNA and protein was detected in the adrenal medulla during 60-min stress. Similarly, in rats undergoing sympathetic nerve block with propranolol, BDNF mRNA and protein were detected in the adrenal medulla during 60-min stress. These results suggest that signal transduction of TrkB in the adrenal medulla evokes catecholamine release. In addition, catecholamine release was evoked by both the hypothalamic–pituitary–adrenal axis and autocrine signaling by BDNF in the adrenal gland. BDNF–TrkB interaction may play a role in a positive feedback loop in the adrenal medulla during immobilization stress. PMID:23017014

  5. Induction by Glucocorticoids of Angiotensin Converting Enzyme Production from Bovine Endothelial Cells in Culture and Rat Lung In Vivo

    PubMed Central

    Mendelsohn, F. A. O.; Lloyd, C. J.; Kachel, C.; Funder, J. W.

    1982-01-01

    The effect of corticosteroids on angiotensin converting enzyme was investigated in endothelial cell cultures and intact rat lung. Cultured endothelial cells from bovine aorta showed net production of angiotensin converting enzyme (ACE) over 2 d culture in serum-free medium. Dexamethasone (DM) increased cell ACE activity six- to sevenfold at 100 nM with a threshold effect at 0.3 nM. The effect of DM on ACE production was completely inhibited by actinomycin D or cycloheximide. Deoxycorticosterone (DOC) and aldosterone were markedly less active, with a threshold near 100 nM and significant (two to threefold) stimulation of ACE activity at 1 μM. In cells incubated in the presence of 10 nM DM, DOC (10 μM) significantly inhibited ACE production compared with 10 nM DM alone, suggesting that DOC is a partial agonist/partial antagonist in this enzyme system. Protein content of cells or medium was unchanged by steroids at all doses used. In vivo, adrenalectomized rats showed lower pulmonary ACE compared with intact controls, and when injected with DM (40 μg/d for 4 d) showed a significant (twofold, P < 0.002) increase in lung ACE over oil-injected, adrenalectomized controls; serum ACE did not change. Injection with DOC (40 μg/d) or aldosterone (10 μg/d) had no effect on lung or serum ACE. Over a range (0.6 to 2,000 μg) of concentrations of DM administered daily for 7 d, the dose-response curve of DM for induction of pulmonary ACE mirrored that for thymolysis; for both, half-maximal effects were seen at ∼6 μg DM/d, and plateau levels at 60 μg/d. We conclude that glucocorticoids are potent inducers of ACE activity in endothelial cells in culture and in rat lung in vivo, and that the action of aldosterone and DOC reflects occupancy of glucocorticoid receptors. This effect may be of (patho)physiological relevance in regulating levels of ACE in local vascular beds, and thereby modulating local levels of the vasoactive peptides angiotensin II and bradykinin. PMID:6286730

  6. The effects of desensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach in rats depend on the blood glucocorticoid hormone level.

    PubMed

    Podvigina, T T; Bobryshev, P Yu; Bagaeva, T R; Mal'tsev, N A; Levkovich, Yu I; Filaretova, L P

    2009-07-01

    The effects of densensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach were studied before and after administration of indomethacin at an ulcerogenic dose in adrenalectomized rats receiving and not receiving replacement therapy with corticosterone and in sham-operated animals. Measures of the microcirculation consisted of blood flow rates in microvessels in the submucous layer of the stomach and the diameter and permeability of microvessels in the mucosa. Desensitization of capsaicin-sensitive afferent neurons was performed by administration of capsaicin at a dose of 100 mg/kg for two weeks and adrenalectomy one week before the experiment. Blood flow rates in microvessels and microvessel diameters were assessed in non-anesthetized rats by direct video recording methods using a special optical system with a contact dark-field epiobjective. Administration of indomethacin at an ulcerogenic dose led to decreases in blood flow rate in microvessels in the submucous layer, dilation of superficial microvessels in the mucosa of the stomach, and an increase in their permeability. Desensitization of capsaicin-sensitive neurons potentiated indomethacin-induced impairments to the microcirculation in the submucous layer and the mucosa of the stomach. These effects of densensitization were significantly enhanced in conditions of glucocorticoid hormone deficiency. Thus, glucocorticoid hormones have favorable effects on the gastric microcirculation in rats with desensitization of capsaicin-sensitive afferent neurons.

  7. Forced desynchrony reveals independent contributions of suprachiasmatic oscillators to the daily plasma corticosterone rhythm in male rats.

    PubMed

    Wotus, Cheryl; Lilley, Travis R; Neal, Adam S; Suleiman, Nicole L; Schmuck, Stefanie C; Smarr, Benjamin L; Fischer, Brian J; de la Iglesia, Horacio O

    2013-01-01

    The suprachiasmatic nucleus (SCN) is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl-) and dorsomedial (dm-) SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH) rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.

  8. Differential entrainment of peripheral clocks in the rat by glucocorticoid and feeding.

    PubMed

    Sujino, Mitsugu; Furukawa, Keiichi; Koinuma, Satoshi; Fujioka, Atsuko; Nagano, Mamoru; Iigo, Masayuki; Shigeyoshi, Yasufumi

    2012-05-01

    The suprachiasmatic nucleus is the master circadian clock and resets the peripheral clocks via various pathways. Glucocorticoids and daily feeding are major time cues for entraining most peripheral clocks. However, recent studies have suggested that the dominant timing factor differs among organs and tissues. In our current study, we reveal differences in the entrainment properties of the peripheral clocks in the liver, kidney, and lung through restricted feeding (RF) and antiphasic corticosterone (CORT) injections in adrenalectomized rats. The peripheral clocks in the kidney and lung were found to be entrained by a daily stimulus from CORT administration, irrespective of the meal time. In contrast, the liver clock was observed to be entrained by an RF regimen, even if daily CORT injections were given at antiphase. These results indicate that glucocorticoids are a strong zeitgeber that overcomes other entrainment factors regulating the peripheral oscillators in the kidney and lung and that RF is a dominant mediator of the entrainment ability of the circadian clock in the liver.

  9. Sex difference in glucocorticoid binding in rat pituitary is estrogen dependent

    SciTech Connect

    Turner, B.B. )

    1990-01-01

    Sex-dependent differences in corticosteriod binding were assessed in individual pituitaries from adult male and female rats that had been adrenalectomized 12 h before sacrifice. Soluble binding was assayed in duplicate on LH-20 columns. Gonadally intact females showed significantly less {sup 3}h-dexamethasone binding than did intact males. This difference was confirmed in a second study. However, when ovariectomized females were compared with gondadectomized males, there was no difference in receptor concentration. Estrogen was able to reverse the effect of ovariectomy: ovariectomized females receiving estrogen had significantly fewer receptors than intact males. Progesterone did not antagonize the effect of estrogen in the pituitary. A sex difference was also found in the Type I (mineralocorticoid) receptor sub-population which comprised approximately 10% of the total receptors, with females having fewer receptors than males. These results demonstrate that in the pituitary, the level of functional corticosteriod receptors is subject to a 20% down-regulation by circulating levels of estrogen. This raises the possibility that the lower number of receptors in females may act to reduce their sensitivity to the negative feedback effects of glucocorticoids at the level of the pituitary.

  10. Surgical adrenalectomy with diurnal corticosterone replacement slows escalation and prevents the augmentation of cocaine-induced reinstatement in rats self-administering cocaine under long-access conditions.

    PubMed

    Mantsch, John R; Baker, David A; Serge, Joseph P; Hoks, Michael A; Francis, David M; Katz, Eric S

    2008-03-01

    The loss of control over cocaine use and persistently heightened susceptibility to drug relapse that define human cocaine addiction are consequences of drug-induced neuroplasticity and can be studied in rats self-administering cocaine under conditions of daily long access (LgA) as escalating patterns of drug intake and heightened susceptibility to reinstatement. This study investigated the potential contribution of elevated glucocorticoids at the time of LgA cocaine self-administration (SA) to these behavioral indices of addiction-related neuroplasticity. Rats provided 14 days of 6-h access (LgA) to cocaine showed a progressive escalation of SA and were more susceptible to cocaine-induced reinstatement (10 mg/kg, i.p.) compared to rats self-administering under short-access (ShA; 2 h) conditions. A surgical adrenalectomy and corticosterone replacement (ADX/C) regimen that eliminated SA-induced increases in corticosterone (CORT) while maintaining the diurnal pattern of secretion failed to alter SA or reinstatement in ShA rats but slowed escalation and attenuated later reinstatement in LgA rats when applied before but not after chronic LgA SA testing. Although the contribution of other adrenal hormones cannot be ruled out, these data suggest that elevated glucocorticoids at the time of cocaine exposure may be required for the effects of LgA SA on cocaine intake and later reinstatement. The inability of daily CORT administration before daily ShA SA, at a dose that reproduced the response during LgA SA, to mimic the effects of LgA SA suggests that elevated glucocorticoids during SA may play a permissive role in cocaine-induced neuroplasticity that contributes to addiction.

  11. Labeling of hepatic glycogen after short- and long-term stimulation of glycogen synthesis in rats injected with 3H-galactose

    SciTech Connect

    Michaels, J.E.; Garfield, S.A.; Hung, J.T.; Cardell, R.R. Jr. )

    1990-08-01

    The effects of short- and long-term stimulation of glycogen synthesis elicited by dexamethasone were studied by light (LM) and electron (EM) microscopic radioautography (RAG) and biochemical analysis. Adrenalectomized rats were fasted overnight and pretreated for short- (3 hr) or long-term (14 hr) periods with dexamethasone prior to intravenous injection of tracer doses of 3H-galactose. Analysis of LM-RAGs from short-term rats revealed that about equal percentages (44%) of hepatocytes became heavily or lightly labeled 1 hr after labeling. The percentage of heavily labeled cells increased slightly 6 hr after labeling, and unlabeled glycogen became apparent in some hepatocytes. The percentage of heavily labeled cells had decreased somewhat 12 hr after labeling, and more unlabeled glycogen was evident. In the long-term rats 1 hr after labeling, a higher percentage of heavily labeled cells (76%) was observed compared to short-term rats, and most glycogen was labeled. In spite of the high amount of labeling seen initially, the percentage of heavily labeled hepatocytes had decreased considerably to 55% by 12 hr after injection; and sparsely labeled and unlabeled glycogen was prevalent. The EM-RAGs of both short- and long-term rats were similar. Silver grains were associated with glycogen patches 1 hr after labeling; 12 hr after labeling, the glycogen patches had enlarged; and label, where present, was dispersed over the enlarged glycogen clumps. Analysis of DPM/mg tissue corroborated the observed decrease in label 12 hr after administration in the long-term animals. The loss of label observed 12 hr after injection in the long-term pretreated rats suggests that turnover of glycogen occurred during this interval despite the net accumulation of glycogen that was visible morphologically and evident from biochemical measurement.

  12. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism.

    PubMed Central

    May, R C; Kelly, R A; Mitch, W E

    1986-01-01

    Metabolic acidosis is associated with enhanced renal ammonia-genesis which is regulated, in part, by glucocorticoids. The interaction between glucocorticoids and chronic metabolic acidosis on nitrogen utilization and muscle protein metabolism is unknown. In rats pair-fed by gavage, we found that chronic acidosis stunted growth and caused a 43% increase in urinary nitrogen and an 87% increase in urinary corticosterone. Net protein degradation in incubated epitrochlearis muscles from chronically acidotic rats was stimulated at all concentrations of insulin from 0 to 10(4) microU/ml. This effect of acidosis persisted despite supplementation of the media with amino acids with or without insulin, indomethacin, and inhibitors of lysosomal thiol cathepsins. Acidosis did not change protein synthesis; hence, the increase in net protein degradation was caused by stimulation of proteolysis. Acidosis did not increase glutamine production in muscle. The protein catabolic effect of acidosis required glucocorticoids; protein degradation was stimulated in muscle of acidotic, adrenalectomized rats only if they were treated with dexamethasone. Moreover, when nonacidotic animals were given 3 micrograms/100 g of body weight dexamethasone twice a day, muscle protein degradation was increased if the muscles were simply incubated in acidified media. We conclude that chronic metabolic acidosis depresses nitrogen utilization and increases glucocorticoid production. The combination of increased glucocorticoids and acidosis stimulates muscle proteolysis but does not affect protein synthesis. These changes in muscle protein metabolism may play a role in the defense against acidosis by providing amino acid nitrogen to support the glutamine production necessary for renal ammoniagenesis. PMID:3511100

  13. Covalent affinity labeling, radioautography, and immunocytochemistry localize the glucocorticoid receptor in rat testicular Leydig cells

    SciTech Connect

    Stalker, A.; Hermo, L.; Antakly, T. )

    1989-12-01

    The presence and distribution of glucocorticoid receptors in the rat testis were examined by using 2 approaches: in vivo quantitative radioautography and immunocytochemistry. Radioautographic localization was made possible through the availability of a glucocorticoid receptor affinity label, dexamethasone 21-mesylate, which binds covalently to the glucocorticoid receptor, thereby preventing dissociation of the steroid-receptor complex. Adrenalectomized adult rats were injected with a tritiated (3H) form of this steroid into the testis and the tissue was processed for light-microscope radioautography. Silver grains were observed primarily over the Leydig cells of the interstitial space and to a lesser extent, over the cellular layers which make up the seminiferous epithelium, with no one cell type showing preferential labeling. To determine the specificity of the labeling, a 25- or 50-fold excess of unlabeled dexamethasone was injected simultaneously with the same dose of (3H)-dexamethasone 21-mesylate. In these control experiments, a marked reduction in label intensity was noted over the Leydig as well as tubular cells. Endocytic macrophages of the interstitium were non-specifically labeled, indicating uptake of the ligand possibly by fluid-phase endocytosis. A quantitative analysis of the label confirmed the presence of statistically significant numbers of specific binding sites for glucocorticoids in both Leydig cells and the cellular layers of the seminiferous epithelium; 86% of the label was found over Leydig cells, and only 14% over the cells of the seminiferous epithelium. These binding data were confirmed by light-microscope immunocytochemistry using a monoclonal antibody to the glucocorticoid receptor.

  14. Corticosterone regulates expression of BDNF and trkB but not NT-3 and trkC mRNA in the rat hippocampus.

    PubMed

    Schaaf, M J; Hoetelmans, R W; de Kloet, E R; Vreugdenhil, E

    1997-05-15

    Corticosterone has profound effects on growth, differentiation, and synaptic transmission of hippocampal neurons by activation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). In the present study we tested if neurotrophins can be implicated in these effects. For this purpose we injected 30, 300, and 1,000 microg corticosterone s.c. (per kg body weight) in adrenalectomized rats and measured the mRNA levels of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase (trk)B, neurotrophin (NT)-3, and trkC in hippocampal cell fields at 6 hr after steroid administration by in situ hybridization. NT-3 and trkC mRNA did not show significant changes in any hippocampal region after the various doses of corticosterone. BDNF mRNA decreased after corticosterone administration dose dependently, resulting in a maximal suppression of 35, 20, and 50% in dentate gyrus, CA3, and CA1, respectively. Interestingly, trkB responded to corticosterone in an inverted U-shaped fashion in CA3 and dentate gyrus: the low dose of corticosterone increased trkB mRNA expression in both regions by approximately 30%, while the effect of the two higher doses was not different from the vehicle injected controls. In conclusion, we found differential effects of low and high doses of corticosterone on BDNF and trkB expression in hippocampus, which suggests involvement of a coordinated MR- and GR-mediated action.

  15. Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

    PubMed Central

    Chen, Kuey-Chu; Blalock, Eric M.; Curran-Rauhut, Meredith A.; Kadish, Inga; Blalock, Susan J.; Brewer, Lawrence; Porter, Nada M.

    2013-01-01

    Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the long-standing hypothesis that chronic GC exposure promotes brain aging/Alzheimer disease. Here, we adrenalectomized male F344 rats at 15 months of age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid receptor–activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between intermediate and low CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT–up-regulated genes included learning/plasticity, differentiation, glucose metabolism, and cholesterol biosynthesis, whereas processes overrepresented by CORT–down-regulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC transcriptome with a previously defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same direction, the majority were shifted in opposite directions by CORT and aging (eg, glial inflammatory genes down-regulated by CORT are up-regulated with aging). These results contradict the hypothesis that GCs simply promote brain aging and also suggest that the opposite direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways, whereas GC overstimulation develops in others, together generating much of the

  16. Formation of C21 bile acids from plant sterols in the rat

    SciTech Connect

    Boberg, K.M.; Lund, E.; Olund, J.; Bjoerkhem, I. )

    1990-05-15

    Formation of bile acids from sitosterol in bile-fistulated female Wistar rats was studied with use of 4-14C-labeled sitosterol and sitosterol labeled with 3H in specific positions. The major part (about 75%) of the 14C radioactivity recovered as bile acids in bile after intravenous administration of (4-14C)sitosterol was found to be considerably more polar than cholic acid, and only trace amounts of radioactivity had chromatographic properties similar to those of cholic acid and chenodeoxycholic acid. It was shown that polar metabolites were formed by intermediate oxidation of the 3 beta-hydroxyl group (loss of 3H from 3 alpha-3H-labeled sitosterol) and that the most polar fraction did not contain a hydroxyl group at C7 (retention of 3H in 7 alpha,7 beta-3H2-labeled sitosterol). Furthermore, the polar metabolites had lost at least the terminal 6 or 7 carbon atoms of the side chain (loss of 3H from 22,23-3H2- and 24,28-3H2-labeled sitosterol). Experiments with 3H-labeled 7 alpha-hydroxysitosterol and 4-14C-labeled 26-hydroxysitosterol showed that none of these compounds was an efficient precursor to the polar metabolites. By analysis of purified most polar products of (4-14C) sitosterol by radio-gas chromatography and the same products of 7 alpha,7 beta-(2H2)sitosterol by combined gas chromatography-mass spectrometry, two major metabolites could be identified as C21 bile acids. One metabolite had three hydroxyl groups (3 alpha, 15, and unknown), and one had two hydroxyl groups (3 alpha, 15) and one keto group. Considerably less C21 bile acids were formed from (4-14C)sitosterol in male than in female Wistar rats. The C21 bile acids formed in male rats did not contain a 15-hydroxyl group. Conversion of a (4-14C)sitosterol into C21 bile acids did also occur in adrenalectomized and ovariectomized rats, indicating that endocrine tissues are not involved.

  17. A negative allosteric modulator demonstrates biased antagonism of the follicle stimulating hormone receptor

    PubMed Central

    Dias, James A.; Bonnet, Béatrice; Weaver, Barbara A.; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M.; Poli, Sonia; Mutel, Vincent; Campo, Brice

    2015-01-01

    High quality gamete production in males and females requires the pituitary gonadotropin follicle stimulating hormone (FSH). In this report a novel chemical class of small molecule inhibitors of FSH receptor (FSHR) is described. ADX61623, a negative allosteric modulator (NAM), increased the affinity of interaction between 125I-hFSH and human FSHR (hFSHR) five fold. This form of FSHR occupied simultaneously by FSH and ADX61623 was inactive for cAMP and progesterone production in primary cultures of rat granulosa cells. In contrast, ADX61623 did not block estrogen production. This demonstrates for the first time, biased antagonism at the FSHR. To determine if ADX61623 blocked FSH induction of follicle development in vivo, a bioassay to measure follicular development and oocyte production in immature female rats was validated. ADX61623 was not completely effective in blocking FSH induced follicular development in vivo at doses up to 100 mg/kg as oocyte production and ovarian weight gain were only moderately reduced. These data illustrate that FSHR couples to multiple signaling pathways in vivo. Suppression of one pool of FSHR uncouples Gαs and cAMP production, and decreases progesterone production. Occupancy of another pool of FSHR sensitizes granulosa cells to FSH induced estradiol production. Therefore, ADX61623 is a useful tool to investigate further the mechanism of the FSHR signaling dichotomy. This may lead to a greater understanding of the signaling infrastructure which enables estrogen biosynthesis and may prove useful in treating estrogen dependent disease. PMID:21184806

  18. Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation

    NASA Technical Reports Server (NTRS)

    Wing, S. S.; Haas, A. L.; Goldberg, A. L.

    1995-01-01

    The rapid loss of skeletal-muscle protein during starvation and after denervation occurs primarily through increased rates of protein breakdown and activation of a non-lysosomal ATP-dependent proteolytic process. To investigate whether protein flux through the ubiquitin (Ub)-proteasome pathway is enhanced, as was suggested by related studies, we measured, using specific polyclonal antibodies, the levels of Ub-conjugated proteins in normal and atrophying muscles. The content of these critical intermediates had increased 50-250% after food deprivation in the extensor digitorum longus and soleus muscles 2 days after denervation. Like rates of proteolysis, the amount of Ub-protein conjugates and the fraction of Ub conjugated to proteins increased progressively during food deprivation and returned to normal within 1 day of refeeding. During starvation, muscles of adrenalectomized rats failed to increase protein breakdown, and they showed 50% lower levels of Ub-protein conjugates than those of starved control animals. The changes in the pools of Ub-conjugated proteins (the substrates for the 26S proteasome) thus coincided with and can account for the alterations in overall proteolysis. In this pathway, large multiubiquitinated proteins are preferentially degraded, and the Ub-protein conjugates that accumulated in atrophying muscles were of high molecular mass (> 100 kDa). When innervated and denervated gastrocnemius muscles were fractionated, a significant increase in ubiquitinated proteins was found in the myofibrillar fraction, the proteins of which are preferentially degraded on denervation, but not in the soluble fraction. Thus activation of this proteolytic pathway in atrophying muscles probably occurs initially by increasing Ub conjugation to cell proteins. The resulting accumulation of Ub-protein conjugates suggests that their degradation by the 26S proteasome complex subsequently becomes rate-limiting in these catabolic states.

  19. Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo.

    PubMed Central

    Lu, S C; Ge, J L; Kuhlenkamp, J; Kaplowitz, N

    1992-01-01

    We reported that glucagon and phenylephrine decrease hepatocyte GSH by inhibiting gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis (Lu, S.C., J. Kuhlenkamp, C. Garcia-Ruiz, and N. Kaplowitz. 1991. J. Clin. Invest. 88:260-269). In contrast, we have found that insulin (In, 1 microgram/ml) and hydrocortisone (HC, 50 nM) increased GSH of cultured hepatocytes up to 50-70% (earliest significant change at 6 h) with either methionine or cystine alone as the sole sulfur amino acid in the medium. The effect of In occurred independent of glucose concentration in the medium. Changes in steady-state cellular cysteine levels, cell volume, GSH efflux, or expression of gamma-glutamyl transpeptidase were excluded as possible mechanisms. Both hormones are known to induce cystine/glutamate transport, but this was excluded as the predominant mechanism since the induction in cystine uptake required a lag period of greater than 6 h, and the increase in cell GSH still occurred when cystine uptake was blocked. Assay of GSH synthesis in extracts of detergent-treated cells revealed that In and HC increased the activity of GCS by 45-65% (earliest significant change at 4 h) but not GSH synthetase. In and HC treatment increased the Vmax of GCS by 31-43% with no change in Km. Both the hormone-mediated increase in cell GSH and GCS activity were blocked with either cycloheximide or actinomycin D. Finally, when studied in vivo, streptozotocin-treated diabetic and adrenalectomized rats exhibited lower hepatic GSH levels and GCS activities than respective controls. Both of these abnormalities were prevented with hormone replacement. Thus, both in vitro and in vivo, In and glucocorticoids are required for normal expression of GCS. Images PMID:1353765

  20. Rats! Oh No, Not Rats!

    ERIC Educational Resources Information Center

    Strong, Gary E.

    1987-01-01

    Examples of problems encountered in a new library building--including rats and humidity--and a description of the library's collections provide a framework for this presentation of the California State Library's emergency management planning. Current preservation efforts are documented and the library's disaster and security plans are described.…

  1. Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

    SciTech Connect

    Jacobson, L.

    1989-01-01

    There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain ({sup 14}C)-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain ({sup 14}C)-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO{sub 2} correlated with the severity of hypoxia at arterial PCO{sub 2} below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O{sub 2}.

  2. Role of glucocorticoids in increased muscle glutamine production in starvation

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Henriksen, Erik J.; Cook, Paul H.

    1988-01-01

    The role of glucocorticoids in the synthesis of muscle glutamine during starvation was investigated in adrenalectomized fasted rats injected with cortisol (1 mg/100 g body weight). It was found that administration of cortisol in vivo increased (compared to nontreated starved adrenalectomized controls) the glutamine/glutamate ratio and the activity of glutamine synthetase in the diaphragm and the extensor digitorum muscles, and that these effects were abolished by prior treatment with actinomycin D or proflavine. The results obtained in in vitro experiments, using fresh-frozen soleus, extensor digitorum longus, and diaphragm muscle preparations, supported the in vivo indications of the cortisol-enhanced glutamine synthesis and protein turnover in starved adrenalectomized animals.

  3. No evidence of rat hepatitis E virus excretion into urine of rats.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Johne, Reimar; Wakita, Takaji

    2016-08-31

    To investigate whether rat hepatitis E virus (rat HEV) is excreted into the urine of rats, we infected three Wistar and six nude rats with rat HEV and examined the rat HEV RNA in serum, fecal and urine samples. We detected rat HEV RNA in the serum and fecal samples of all rats but not in the urine. Our results suggest that in rats, rat HEV is not transmitted via urine.

  4. Development of an Assay for the Early Detection of Organ Specific Carcinogenesis by the Determination and Turnover of NAD(+) and Polyadenosine Diphosphoribose

    DTIC Science & Technology

    1980-10-28

    normal hypophy- sectomized and adrenalectomized rats suggested a direct regulatory influence of steriods on nuclear poly(ADP-R) metabolism. If this is a...Interaction of steriod hormones with the nucleus. Pharmacological Reviews 30: 477-491 Jump DB, Butt TR and Smulson M (1979) Nuclear protein mod

  5. Rat Bite Fever

    MedlinePlus

    ... Ear Nose & Throat Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth ... Preventable Diseases Healthy Children > Health Issues > Conditions > From Insects or Animals > Rat Bite Fever Health Issues Listen ...

  6. Rat-bite fever

    MedlinePlus

    Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are found in ...

  7. What is Desert RATS?

    NASA Video Gallery

    The mission manager and test coordinators for the 2011 mission explain why Desert RATS was started 14 years ago, questions being studied in this year's activities, technologies being tested and the...

  8. [Fatal rat bites].

    PubMed

    Yanai, O; Goldin, L; Hiss, J

    1999-04-15

    We present a rare case of infant death due to blood loss resulting from multiple rat bites. Domestic dogs and cats cause most animal bites. Bites of a house rat usually cause bacterial infection, successfully treated with antibiotics. There is little information about death due to house rat bites. Since the wounds they cause tend to occur post-mortem, they are usually wedged, clean and without subcutaneous bleeding. An 11-week-old, malnourished infant girl was bitten to death while sleeping in her mother's bed in a rat-infested home. The infant's clothing was covered with blood, parts of her face were missing and marks of gnawing were present on her neck and extremities. There was subcutaneous bleeding around the wounds indicating that they were inflicted while the child was alive. Autopsy findings revealed profound blood loss. We conclude that a combination of low socio-economic status, severe failure to thrive, and poor hygiene in a rat-infested environment contributed to the fatal outcome in this attack.

  9. Rat on Mars

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image taken on Mars by the panoramic camera on the Mars Exploration Rover Opportunity shows the rover's rock abrasion tool, also known as 'rat' (circular device in center), located on its instrument deployment device, or 'arm.' The image was acquired on the ninth martian day or sol of the rover's mission.

  10. Culturing rat hippocampal neurons.

    PubMed

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  11. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-09-28

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups.

  12. Rat retinal transcriptome

    PubMed Central

    Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Natalia G.

    2013-01-01

    Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy. PMID:23656783

  13. An anti-aldosteronic diuretic component (drain dampness) in Polyporus sclerotium.

    PubMed

    Yuan, Dan; Mori, Junna; Komatsu, Ken-ich; Makino, Toshiaki; Kano, Yoshihiro

    2004-06-01

    Polyporus Sclerotium botanically from the Polyporus umbellatus (PERS.) FRIES, was traditionally used for the purpose of promoting diuresis. The present study investigated the diuretic effect of ergosta-4,6,8(14),22-tetraen-3-one (ergone) which is a maker component according to the chemical assay for its quality standardization. It resulted in a reversion to ordinary value of the urinary ratio of Na/K in deoxycoricosterone acetate (DOCA)-treated and adrenalectomized rats, although it had no this effect on the Na or K contents as well as Na/K value both in normal rats and in adrenalectomized rats without DOCA. These data indicate that ergone possesses an anti-aldosteronic diuretic effect. Moreover, it was identified in the blood and bile of rats after its administration to the gastrointestinal tract. The above results demonstrate that it is an active component of Polyporus Sclerotium.

  14. Gravitational Biology: The Rat Model

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  15. Rat Endovascular Perforation Model

    PubMed Central

    Sehba, Fatima A.

    2014-01-01

    Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The Rat endovascular perforation model (EVP) replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH. This paper presents a brief review of historical development of the EVP model, details the technique used to create SAH and considerations necessary to overcome technical challenges. PMID:25213427

  16. Development of an exchange assay for cytosolic glucocorticoid receptors using the synergistic effects of molybdate plus dithiothreitol

    SciTech Connect

    Kalimi, M.; Hubbard, J.R.

    1983-09-01

    A glucocorticoid receptor exchange assay has been developed for the accurate quantification of both free and steroid-bound receptors in rat liver cytosol. Hepatic cytosol from adrenalectomized rats was saturated in vitro with unlabeled corticosterone. Cytosol was subsequently treated with (/sup 3/H)dexamethasone (with and without 1000-fold cold dexamethasone) for 2-28 h at 4 C in the presence of 10 mM molybdate plus 5 mM dithiothreitol (DTT). Complete exchange occurred between 16-28 h in the presence of molybdate plus DTT. In control and 10 mM molybdate (alone) treated samples only about 50% exchange was achieved. In the presence of 5 mM DTT (alone) approximately 60-70% exchange was observed. The exchange assay (utilizing molybdate plus DTT) was also applied to hepatic cytosol of adrenalectomized rats injected with corticosterone in vivo and to samples prebound with unlabeled dexamethasone.

  17. War on Rats, 1972 Progress Report.

    ERIC Educational Resources Information Center

    District of Columbia Dept. of Environmental Services, Washington, DC.

    The City of Washington, D.C., with federal funding, declared war on one of the city's most pressing problems--rats. The War on Rats Program, in conjunction with Operation Clean Sweep, made a city-wide survey of rat infestations and recorded the areas of heavy rat infestation. After the problem areas had been identified, community organizations…

  18. Do rats have orgasms?

    PubMed Central

    Pfaus, James G.; Scardochio, Tina; Parada, Mayte; Gerson, Christine; Quintana, Gonzalo R.; Coria-Avila, Genaro A.

    2016-01-01

    Background Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs) in other species: 1) physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2) short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3) long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results Both male and female rats display behavioral patterns consistent with OLRs. Conclusions The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research. PMID:27799081

  19. Glucocorticoids mediate circadian timing in peripheral osteoclasts resulting in the circadian expression rhythm of osteoclast-related genes.

    PubMed

    Fujihara, Yuko; Kondo, Hisataka; Noguchi, Toshihide; Togari, Akifumi

    2014-04-01

    Circadian rhythms are prevalent in bone metabolism. However, the molecular mechanisms involved are poorly understood. Recently, we suggested that output signals from the suprachiasmatic nucleus (SCN) are transmitted from the master circadian rhythm to peripheral osteoblasts through β-adrenergic and glucocorticoid signaling. In this study, we examined how the master circadian rhythm is transmitted to peripheral osteoclasts and the role of clock gene in osteoclast. Mice were maintained under 12-hour light/dark periods and sacrificed at Zeitgeber times 0, 4, 8, 12, 16 and 20. mRNA was extracted from femur (cancellous bone) and analyzed for the expression of osteoclast-related genes and clock genes. Osteoclast-related genes such as cathepsin K (CTSK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) showed circadian rhythmicity like clock genes such as period 1 (PER1), PER2 and brain and muscle Arnt-like protein 1 (BMAL1). In an in vitro study, not β-agonist but glucocorticoid treatment remarkably synchronized clock and osteoclast-related genes in cultured osteoclasts. Chromatin immunoprecipitation (ChIP) assay showed the interaction between BMAL1 proteins and promoter region of CTSK and NFATc1. To examine whether endogenous glucocorticoids influence the osteoclast circadian rhythms, mice were adrenalectomized (ADX) and maintained under 12-hour light/dark periods at least two weeks before glucocorticoid injection. A glucocorticoid injection restarted the circadian expression of CTSK and NFATc1 in ADX mice. These results suggest that glucocorticoids mediate circadian timing to peripheral osteoclasts and osteoclast clock contributes to the circadian expression of osteoclast-related genes such as CTSK and NFATc1.

  20. Generation of Hprt-disrupted rat through mouse←rat ES chimeras

    PubMed Central

    Isotani, Ayako; Yamagata, Kazuo; Okabe, Masaru; Ikawa, Masahito

    2016-01-01

    We established rat embryonic stem (ES) cell lines from a double transgenic rat line which harbours CAG-GFP for ubiquitous expression of GFP in somatic cells and Acr3-EGFP for expression in sperm (green body and green sperm: GBGS rat). By injecting the GBGS rat ES cells into mouse blastocysts and transplanting them into pseudopregnant mice, rat spermatozoa were produced in mouse←rat ES chimeras. Rat spermatozoa from the chimeric testis were able to fertilize eggs by testicular sperm extraction combined with intracytoplasmic sperm injection (TESE-ICSI). In the present paper, we disrupted rat hypoxanthine-guanine phosphoribosyl transferase (Hprt) gene in ES cells and produced a Hprt-disrupted rat line using the mouse←rat ES chimera system. The mouse←rat ES chimera system demonstrated the dual advantages of space conservation and a clear indication of germ line transmission in knockout rat production. PMID:27062982

  1. Postural development in rats.

    PubMed

    Lelard, T; Jamon, M; Gasc, J-P; Vidal, P-P

    2006-11-01

    Mammals adopt a limited number of postures during their day-to-day activities. These stereotyped skeletal configurations are functionally adequate and limit the number of degrees of freedom to be controlled by the central nervous system. The temporal pattern of emergence of these configurations in altricial mammals is unknown. We therefore carried out an X-ray study in unrestrained rats from birth (P0) until postnatal day 23 (P23). The X-rays showed that many of the skeletal configurations described in adult rodents were already present at birth. By contrast, limb placement changed abruptly at around P10. These skeletal configurations, observed in anesthetized pups, required the maintenance of precise motor control. On the other hand, motor control continued to mature, as shown by progressive changes in resting posture and head movements from P0 to P23. We suggest that a few innate skeletal configurations provide the necessary frames of reference for the gradual construction of an adult motor repertoire in altricial mammals, such as the rat. The apparent absence of a requirement for external sensorial cues in the maturation of this repertoire may account for the maturation of postural and motor control in utero in precocial mammals (Muir et al., 2000 for a review on the locomotor behavior of altricial and precocial animals).

  2. Male rat sexual behavior.

    PubMed

    Agmo, A

    1997-05-01

    The male rat's sexual behavior constitutes a highly ordered sequence of motor acts involving both striate and smooth muscles. It is spontaneously displayed by most adult made rats in the presence of a sexually receptive female. Although the behavior is important for the survival of the species it is not necessary for survival of the individual. In that way it is different from other spontaneous behaviors such as eating, drinking, avoidance of pain, respiration or thermoregulation. Among other things, this means that it is difficult to talk about sexual deprivation or need. Nevertheless, studies of male sex behavior distinguish sexual motivation (the ease by which behavior is activated, "libido") from the execution of copulatory acts (performance, "potency") (Meisel, R.L. and Sachs, B.D., The physiology of male sexual behavior. In: E. Knobil and J.D. Neill (Eds.), The Physiology of Reproduction, 2nd Edn., Vol. 2, Raven Press, New York, 1994, pp. 3-105 [13]). The hormonal control of male sexual behavior has been extensively studied. It is clear that steroid hormones, androgens and estrogens, act within the central nervous system, modifying neuronal excitability. The exact mechanism by which these hormones activate sex behavior remains largely unknown. However, there exists a considerable amount of knowledge concerning the brain structures important for sexual motivation and for the execution of sex behavior. The modulatory role of some non-steroid hormones is partly known, as well as the consequences of manipulations of several neurotransmitter systems.

  3. Pathogenesis and Transmission of Kilham Rat Virus Infection in Rats

    PubMed Central

    Novotny, James F.; Hetrick, Frank M.

    1970-01-01

    The Kilham rat virus (RV) was found to produce mortality in newborn rats after intracerebral, intravenous, or subcutaneous administration of virus. Both infectious virus and viral hemagglutinins were detected in a variety of tissues and in the blood and urine of experimentally infected rats. Contact control rats housed with infected littermates did not develop disease but did produce antibody to RV. Horizontal virus transmission was also evidenced by the seroconversion of antibody-negative mothers whose litters were infected with RV. The level of maternal antibody was found to be the determining factor in the susceptibility or refractiveness of newborn rats to RV infection. If the mother had no detectable hemagglutination-inhibiting (HI) antibody titer (less than 10) or a low antibody titer (10 or 20), her offspring were highly susceptible to RV. However, the litters of rats with HI titers of 40 or greater were afforded protection when challenged with RV; the higher the maternal antibody level the more solid was the protection conferred. Vertical transmission of RV was also demonstrated. Litters born of mothers infected with RV several days before delivery died within 7 to 9 days of a disease identical to that seen in infected newborns and virus was recovered from a variety of tissues. Results of mother-litter exchange experiments also indicated vertical transmission (rather than transmission through milk) occurs, since litters of infected mothers developed the disease when nursed by normal mothers, whereas litters of normal mothers remained normal although they were nursed by infected mothers. PMID:16557835

  4. Online tools for understanding rat physiology

    PubMed Central

    2010-01-01

    Rat models have been used to investigate physiological and pathophysiological mechanisms for decades. With the availability of the rat genome and other online resources, tools to identify rat models that mimic human disease are an important step in translational research. Despite the large number of papers published each year using rat models, integrating this information remains a problem. Resources for the rat genome are continuing to grow rapidly, while resources providing access to rat phenotype data are just emerging. An overview of rat models of disease, tools to characterize strain by phenotype and genotype, and steps being taken to integrate rat physiological data is presented in this article. Integrating functional and physiological data with the rat genome will build a solid research platform to facilitate innovative studies to unravel the mechanisms resulting in disease. PMID:20056729

  5. Hormonal changes in antiorthostatic rats

    NASA Technical Reports Server (NTRS)

    Popovic, V.; Popovic, P.; Honeycutt, C.

    1982-01-01

    Hypokinesia, especially hypokinesia with negative tilt ('antiorthostatic hypokinesia'), mimics some of the effects of weightlessness. It is shown that cardiac output is increased during early exposure of rats to antiorthostatic hypokinesia. The increase of the stroke volume and of the cardiac output observed in the antiorthostatic hypokinetic rats is probably the consequence of a blood volume shift toward the chest brought forth by head-down positioning of the animals. It is also possible that struggling of the animals to escape from the harness and an increased metabolism contribute to the elevation of cardiac output. In order to study this hypothesis 'stress hormones' were measured in the antiorthostatic rats. Plasma levels of ACTH, corticosterone and prolactin were measured in the arterial blood (0.3 ml) sampled before, during and after hypokinesia from chronic aortic cannulas of the rats.

  6. Autoshaping in micrencephalic rats

    SciTech Connect

    Goldstein, L.H.; Oakley, D.A.

    1989-06-01

    An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

  7. Spatial integration with rats.

    PubMed

    Chamizo, V D; Rodrigo, T; Mackintosh, N J

    2006-11-01

    Rats were trained to find the hidden platform in a Morris pool, whose location was defined by reference to a small number of landmarks around the circumference of the pool. In each of three experiments, an experimental group was trained on alternate trials with two different subsets of three of the available landmarks, with the two subsets sharing one landmark in common. When tested with landmarks drawn from both of their training configurations, but without the landmark common to the two sets, they had no difficulty in locating the platform. In Experiment 1, they performed at least as well as a group trained with all the available landmarks present on every trial. In Experiment 2, they performed significantly better than a group trained with two different subsets of landmarks that shared no one landmark in common.

  8. The rat adrenal medulla.

    PubMed

    Tischler, A S

    1989-01-01

    Adult adrenal medullary cells, in many strains of rats, develop diffuse and nodular hyperplasia and neoplasia under a variety of conditions. Both endogenous and exogenous factors affect the development of these proliferative changes. The former include the animals' strain, age, and sex. The latter include drugs and other environmental agents, diet, and perhaps stress. Adrenal medullary neoplasms which arise under diverse circumstances often closely resemble each other both morphologically and functionally, and exhibit characteristics of immature chromaffin cells. Recent data indicate that normal, mature-appearing epinephrine- and norepinephrine-type chromaffin cells are able to divide, and suggest that signals which regulate chromaffin cell function also regulate cell proliferation. Prolongation of these signals or superimposed abnormalities might initiate pathological proliferative states. It remains to be determined whether the mechanisms which promote or prevent cell proliferation in the adult adrenal are related to those involved in normal development.

  9. Social facial touch in rats.

    PubMed

    Wolfe, Jason; Mende, Carolin; Brecht, Michael

    2011-12-01

    We know much about how rats use their whiskers to discriminate simple tactile properties, but little about how they are used in natural settings. Here we studied whisker motion during social interactions between rats in order to gain a better understanding of natural whisker use in this model system for sensorimotor integration. In the first set of experiments, an intruder was placed in a second rat's home cage. Anogenital sniffing immediately ensued; later in the trial, facial interactions occurred at least as frequently. Whereas much previous work has focused on the importance of anogenital sniffing during social interactions, these facial interactions were accompanied by some of the most intense whisker behaviors described to date. Whisker trimming increased biting but reduced boxing. In addition, whiskers were more protracted and whisking amplitude was larger in aggressive than in nonaggressive interactions. In a second set of experiments, rats interacted facially across a gap. As rats approached each other, whisking amplitude decreased and whiskers were more protracted. Whisker trimming disrupted facial alignment and reduced the frequency of interactions, indicating that whisker use, and possibly whisker protraction, is important for rats to orient themselves with respect to one another. We also found that females whisked with smaller amplitude when interacting with males than with females, and that they held their whiskers less protracted than males. The natural whisker use described here should further our understanding of this important somatosensory system during social interactions.

  10. Management of an outbreak of rat theilovirus.

    PubMed

    Dyson, Melissa C

    2010-05-01

    Rat theilovirus is a commonly reported infection in research rat colonies. The author's institution experienced an outbreak of rat theilovirus in a breeding colony of unique outbred rats. To manage this outbreak, the institution chose to use a 'test and cull' strategy because this approach is reported to be successful in mouse colonies infected with Theiler's murine encephalomyelitis virus, a related virus. Here the author describes the outbreak and subsequent management of rat theilovirus. The strategy successfully cleared the virus from the rat colony.

  11. False Context Fear Memory in Rats

    ERIC Educational Resources Information Center

    Bae, Sarah; Holmes, Nathan M.; Westbrook, R. Frederick

    2015-01-01

    Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control…

  12. Adenohypophysitis in rat pituitary allografts

    PubMed Central

    Rotondo, Fabio; Quintanar-Stephano, Andres; Asa, Sylvia L; Lombardero, Matilde; Berczi, Istvan; Scheithauer, Bernd W; Horvath, Eva; Kovacs, Kalman

    2010-01-01

    The histological, immunohistochemical and ultrastructural alterations in 81 pituitary allografts from Lewis rats transplanted beneath the renal capsule of Wistar rats were investigated. Intrasellar pituitaries of rats bearing allografts were also examined. Recipient rats were sacrificed at various time points after transplantation. Two days after transplantation, the central portion of the allografts demonstrated ischaemic necrosis. A week later, massive mononuclear cell infiltrates consisting primarily of lymphocytes and to a lesser extent, macrophages, plasma cells and granulocytes became prominent. At about three to four weeks after transplantation, the mononuclear cell infiltrate diminished; the surviving adenohypophysial cells, mainly prolactin (PRL) cells, increased in number and necrosis was replaced by connective tissue. No histological changes were noted in the intrasellar pituitaries of rats bearing allografts. Immunohistochemistry demonstrated that the surviving adenohypophysial cells were mainly PRL-producing cells. Electron microscopy revealed adenohypophysial cell destruction, a spectrum of inflammatory cells and, in late phase, accumulation of fibroblasts and collagen fibres. PRL cells were the prominent cell types; they increased in number. It appears that pituitary allografts are ‘foreign’ and evoke an immune response, suggesting that they may be used as an experimental animal model for morphological investigation of the development and progression of adenohypophysitis, a rare disease occurring mainly in young women often associated with pregnancy. PMID:20586813

  13. Tuberculosis Detection by Giant African Pouched Rats

    ERIC Educational Resources Information Center

    Poling, Alan; Weetjens, Bart; Cox, Christophe; Beyene, Negussie; Durgin, Amy; Mahoney, Amanda

    2011-01-01

    In recent years, operant discrimination training procedures have been used to teach giant African pouched rats to detect tuberculosis (TB) in human sputum samples. This article summarizes how the rats are trained and used operationally, as well as their performance in studies published to date. Available data suggest that pouched rats, which can…

  14. Hematopoiesis in antiorthostatic, hypokinesic rats

    NASA Technical Reports Server (NTRS)

    Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.

    1983-01-01

    Rats exposed to antiorthostatic, hypokinesia showed the following effects which are comparable to those seen in man during or after space flight: weight loss, reduced food and water consumption, transient increases in peripheral hematocrit and RBC count, decreasing MCV and reduced reticulocyte count. In addition, the hemoglobin P50 was shifted to the right. A significant shortening of RBC t1/2 was only seen after suspension. Changes in leukocyte and platelet numbers in suspended rats were also comparable to those in man during space flight, but leukocyte PHA sensitivity in rats showed no consistent alteration. The results demonstrate that this model reproduces many of the hematological effects of space flight and has potential as a tool in understanding the hematopoietic response to zero gravity.

  15. Using rats for vision research.

    PubMed

    Reinagel, P

    2015-06-18

    A wide variety of species are used for the study of visual neuroscience. This is beneficial because fundamental mechanisms and theoretical principles of vision are likely to be highly conserved, while different species exhibit different visual capacities and present different technical advantages for experiments. Eight years ago my laboratory adopted the hooded rat as our primary preparation for vision research. To some this may be surprising, as nocturnal rodents have often been presumed to have poor vision and weak visual behavior. This commentary will provide my personal perspective on how I came to work with rats; discuss an example research project for which rats have been advantageous; and comment on the opportunities and challenges of the preparation.

  16. Voluntary Sleep Loss in Rats

    PubMed Central

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  17. Swimming-based pica in rats.

    PubMed

    Nakajima, Sadahiko

    2016-09-01

    We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats.

  18. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Yasuda, Shumpei P; Yoshimatsu, Kumiko; Arikawa, Jiro; Takeda, Naokazu; Wakita, Takaji

    2013-04-12

    To determine whether or not rats are susceptible to hepatitis E virus (HEV) infection, each of group containing three laboratory rats (Wistar) were experimentally inoculated with genotypes 1, 3, 4 and rat HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA, respectively. The virus infection was monitored up to 3 months after inoculation. None of the serum or stool samples collected from the rats inoculated with G1, G3, or G4 HEV indicated positive sign for virus replication. Although no alteration was observed in ALT level, rat HEV RNA was detected in stools from both of the rats inoculated with rat HEV, and both rats were positive for anti-rat HEV IgG and IgM from 3 weeks after inoculation. These results demonstrated that rats are susceptible to rat HEV but not to G1, G3, and G4 HEV. We also confirm that the nude rats were useful for obtaining a large amount of rat HEV and that the rat HEV was transmitted by the fecal-oral route.

  19. In vivo tropisms and kinetics of rat theilovirus infection in immunocompetent and immunodeficient rats.

    PubMed

    Drake, Michael T; Besch-Williford, Cindy; Myles, Matthew H; Davis, Justin W; Livingston, Robert S

    2011-09-01

    Rat theilovirus (RTV) is a cardiovirus related to Theiler's murine encephalomyelitis virus. While RTV is a prevalent viral pathogen of rats used in biomedical research, the pathogenesis and characterization of RTV infections is not well understood. In the studies reported herein, we used immunohistochemistry to identify viral antigens in enterocytes of the small intestines of Sprague-Dawley (SD) rats. Fecal viral shedding in immunocompromised and immunocompetent rats following oral gavage with RTV1 was high for the first 2 weeks of infection with persistent shedding of high viral loads being observed in immunocompromised nude rats but not in immunocompetent rats. RTV was also detected in mesenteric lymph nodes and spleen of immunocompromised rats but not immunocompetent rats. In addition, the magnitude of serum antibody responses differed between immunocompetent rat strains with Brown Norway and SD rats having a significantly higher antibody response than CD or Fischer 344 rats. These data suggest that RTV1 has a tropism for the epithelial cells of the small intestine, immunocompetent rats have differing serum antibody responses to RTV infection, and sustained fecal shedding and extraintestinal dissemination of RTV1 occurs in rats deficient in T cell-dependent adaptive immunity. RTV infection in immunocompromised and immunocompetent rats has merit as a model for further studies of theilovirus pathogenesis following oral viral exposure.

  20. Struvite Urolithiasis in Long-Evans Rats.

    PubMed

    Pang, Jassia; Borjeson, Tiffany M; Parry, Nicola M A; Fox, James G

    2015-12-01

    Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long-Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well.

  1. Cloning of rat homeobox genes

    SciTech Connect

    Sakoyama, Yasuhiko; Mizuta, Ikuko; Ogasawara, Naotake

    1994-10-01

    We report the isolation of nine rat cognates of mouse homeoboxes within the four Hox gene clusters and a rat homologue of mouse IPF1 homeobox, RHbox No. 13A. The sequences of nine cloned homeoboxes are highly similar to those of the mouse and human homeoboxes in the Hox clusters. The restriction enzyme sites and map distances between each of the homeoboxes on the rat genome are nearly identical to those of mouse and human. Thus, we conclude that the isolated homeoboxes are the rat homologues of mouse homeoboxes within the four Hox clusters. A novel homeobox RHbox No. 13A is different from the Drosophila Antennapedia (Antp) sequence but is highly similar to the XlHbox8 (Xenopus laevis) and HtrA2 (Helobdella triserialis) homeoboxes. Forty-two amino acids of the last two-thirds of the RHbox No. 13A, XlHbox8, and mouse IPF1 homeodomains completely matched. In addition, these four homeodomains contain a unique His residue in the recognition helix of a helix-turn-helix DNA-binding motif. This His residue is not found in any of the previously published mammalian homeodomain sequences except mouse IPF1. 24 refs., 4 figs.

  2. Whiskers aid anemotaxis in rats

    PubMed Central

    Yu, Yan S. W.; Graff, Matthew M.; Bresee, Chris S.; Man, Yan B.; Hartmann, Mitra J. Z.

    2016-01-01

    Observation of terrestrial mammals suggests that they can follow the wind (anemotaxis), but the sensory cues underlying this ability have not been studied. We identify a significant contribution to anemotaxis mediated by whiskers (vibrissae), a modality previously studied only in the context of direct tactile contact. Five rats trained on a five-alternative forced-choice airflow localization task exhibited significant performance decrements after vibrissal removal. In contrast, vibrissal removal did not disrupt the performance of control animals trained to localize a light source. The performance decrement of individual rats was related to their airspeed threshold for successful localization: animals that found the task more challenging relied more on the vibrissae for localization cues. Following vibrissal removal, the rats deviated more from the straight-line path to the air source, choosing sources farther from the correct location. Our results indicate that rats can perform anemotaxis and that whiskers greatly facilitate this ability. Because air currents carry information about both odor content and location, these findings are discussed in terms of the adaptive significance of the interaction between sniffing and whisking in rodents. PMID:27574705

  3. Dithiobiuret toxicity in the rat

    SciTech Connect

    Williams, K.D.

    1985-01-01

    Raising the daily dose of dithiobiuret (DTB) in male rats from 0.5 to 1 to 5 mg/kg shortened the latency to the onset of flaccid muscle tone and associated diminished performance in a treadmill test from 7 to 5 to 3 days, respectively. Concomitant with the development of flaccid muscle tone gastrocnemius muscle contractions elicited by high frequency motor nerve stimulation were lower in peak tension and tended to fade more rapidly in DTB-treated rats than in control rats. Remarkably, rats treated with highly daily doses (10-16 mg/kg) of DTB were resistant to the expected development of DTB-induced flaccid muscle tone, and tetanic contractile abnormalities but a corresponding refractoriness to body weight loss, decreased fed and water intake, diuresis, and depression in water balance was not present. This nonselectivity of the refractory responses supported the results of a histopathological study indicating that DTB-induced neuromuscular toxicity was unlikely to be secondary to effect on other organ systems. It is not known whether the ultimate neurotoxin is DTB or a metabolite. In this regard, two pathways for the metabolism of DTB were proposed based on the results of thin-layer chromatography of urine samples from rats treated with either /sup 14/C- or /sup 35/S-DTB. One pathway involved the reversible oxidation of DTB to the disulfide-containing compound thiuret, and the other involved the replacement of a sulfur atom with oxygen to form monothiobiuret. Thiuret, but not monothiobiuret, possessed comparable toxicity to STB. This further suggested that redox cycling between DTB and thiuret could be an important contributing factor to the toxicity of DTB.

  4. Sexual dimorphism in hybrids rats.

    PubMed

    Garcia-Falgueras, Alicia; Pinos, Helena; Fernández, Rosa; Collado, Paloma; Pasaro, Eduardo; Segovia, Santiago; Guillamon, Antonio

    2006-12-06

    Laboratory rat strains descend from Wistar rats as a consequence of artificial selection. Previously we reported that the medial posterior division of the bed nucleus of the stria terminalis (BSTMP) was sexually dimorphic in Wistar and Long-Evans strains while the medial anterior division (BSTMA) and the locus coeruleus (LC) only showed sex differences in the ancestor Wistar strain. The lateral posterior division (BSTLP) was isomorphic in both strains. The present work studies the number of neurons in the BSTMP, BSTMA, BSTLP and LC of male and female Wistar and Long-Evans rats (F(0)) and their hybrid F(1) and F(2) generations. The BSTMP is sexually dimorphic in the F(0), F(1) and F(2) generations while sex differences in the LC are only seen in F(0) Wistar rats but not in the F(0) Long-Evans or the F(1) and F(2) hybrid generations. Sex differences in the BSTMA are seen in F(0) Wistar but not in F(0) Long-Evans rats and completely disappear in the F(2) generations. The number of neurons in the LC of both males and females decreased in heterozygotic individuals (F(1)) but increased in homozygotic (F(2)). However, the number of neurons in the BSTMP changes significantly over the generations, although the ratio of neurons (female/male) is stable and unaffected in homo- or heterozygosis. Thus, the mechanism that regulates the neuronal female/male ratio would be different from the one that controls the number of neurons. The facts that sex differences in the BSTMP are not affected by homo- or heterozygosis and that they are seen in several mammalian orders suggest the existence of a "fixed" type of brain sex differences in the Mammalia Class.

  5. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise

    USGS Publications Warehouse

    Muths, E.; Reichman, O. J.

    1996-01-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly “stronger” bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  6. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise.

    PubMed

    Muths, E; Reichman, O J

    1996-08-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly "stronger" bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  7. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  8. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  9. Wound Healing Delay in the ZDSD Rat

    PubMed Central

    A. SUCKOW, MARK; A. GOBBETT, TROY; G. PETERSON, RICHARD

    2017-01-01

    Animal models of diabetic delayed wound healing are essential to the development of strategies to improve clinical approaches for human patients. The Zucker diabetic Sprague Dawley (ZDSD) rat has proved to be an accurate model of diet-induced obesity and diabetes and we evaluated the utility of the ZDSD rat as a model for delayed wound healing associated with diabetes and obesity. Groups of ZDSD and Sprague Dawley (SD) rats were placed on a diabetogenic diet and evaluated two weeks later for hyperglycemia, as a sign of diabetes. Rats with blood glucose levels of >300 mg/dl were considered diabetic and those with blood glucose of <180 mg/dl were considered non-diabetic. All SD rats were non-diabetic. A full-thickness excisional skin wound was created in anesthetized rats using a punch biopsy and wound diameter measured on days 1, 4, 7, 9 and 11. Blood glucose levels and body weights were measured periodically before and after wounding. Diabetic ZDSD rats had significantly greater blood glucose levels than non-diabetic ZDSD and SD rats within 10 days of being placed on the diabetogenic diet. Furthermore, diabetic ZDSD rats initially weighed more than non-diabetic ZDSD and SD rats, however, by the end of the study there was no significant difference in body weight between the ZDSD groups. By day nine, wounds in ZDSD rats were significantly larger than those in SD rats and this persisted until the end of the study at day fourteen. Wounds from all groups were characterized histologically by abundant fibroblast cells, collagen deposition and macrophages. These results demonstrate delayed wound healing in both diabetic and non-diabetic ZDSD rats and suggest that obesity or metabolic syndrome are important factors in wound healing delay. PMID:28064221

  10. Histomorphometric analysis of rat skeleton following spaceflight

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey-Holton, E. R.; Doty, S. B.; Maese, A. C.; Walsh, C. C.

    1987-01-01

    Male Sprague-Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared with data derived from ground-based control rats. Trabecular bone mass was not altered during the 1st wk of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. For the most part, histological indexes of bone resorption were normal in flight rats. The results indicate that 7 days of weightlessness are not of sufficient duration to induce histologically detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the 1st wk of spaceflight.

  11. Hyperammonemia in anorectic tumor-bearing rats

    SciTech Connect

    Chance, W.T.; Cao, L.; Nelson, J.L.; Foley-Nelson, T.; Fischer, J.E.

    1988-01-01

    Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

  12. Hyperammonemia in anorectic tumor-bearing rats.

    PubMed

    Chance, W T; Cao, L; Nelson, J L; Foley-Nelson, T; Fischer, J E

    1988-01-01

    Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

  13. Automatic Training of Rat Cyborgs for Navigation.

    PubMed

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs.

  14. Toxicity and repellency to rats of actidione

    USGS Publications Warehouse

    Traub, R.; DeWitt, J.B.; Welch, J.F.; Newman, D.

    1950-01-01

    The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst,rather than accept water containing l.0 mg. of actidione per liter. The compound is highly toxic to .rats with the minimum .lethal dose by oral administration being approximately l.0 mg./Kg body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar .untreated boards were pierced within thirty-to sixty minutes.

  15. Automatic Training of Rat Cyborgs for Navigation

    PubMed Central

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs. PMID:27436999

  16. Isolation of rat adrenocortical mitochondria

    SciTech Connect

    Solinas, Paola; Fujioka, Hisashi; Tandler, Bernard; Hoppel, Charles L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  17. Immunochemistry of Rat Lung Tumorigenesis

    DTIC Science & Technology

    1983-01-01

    Memorial Institute 1640 (RPMI) tissue culture medium. The extra tissue surrounding the organs is dissected free and discarded; this procedure is done in a...concentration of 0.5 x 106 cells/ml in a total volume of 3 ml/culture using the following medium: Roswell Park Memorial Institute 1640 (RPMI 1640...test tubes containing sterile Roswel] Park Memorial Institute (RPMI) tissue culture medium 1640. Lymphocytes from rat spleens were isolated, counted and

  18. Methanethiol metabolism in the rat

    SciTech Connect

    Derr, R.F.; Draves, K.

    1983-03-01

    Methanethiol is associated with hepatic failure in humans and the synergistic action of methanethiol, ammonia and octanoate is sufficient to account for the coma of experimental hepatic necrosis. The sulfur atom of methanethiol is eliminated from the body as urinary sulfate at a rate which is approximated by a hyperbola such that 94% is excreted within 21 h after administration. Rats in octanoate or hepatic coma excreted only little sulfate in their urine.

  19. Do rats learn conditional independence?

    PubMed Central

    Timberlake, William

    2017-01-01

    If acquired associations are to accurately represent real relevance relations, there is motivation for the hypothesis that learning will, in some circumstances, be more appropriately modelled, not as direct dependence, but as conditional independence. In a serial compound conditioning experiment, two groups of rats were presented with a conditioned stimulus (CS1) that imperfectly (50%) predicted food, and was itself imperfectly predicted by a CS2. Groups differed in the proportion of CS2 presentations that were ultimately followed by food (25% versus 75%). Thus, the information presented regarding the relevance of CS2 to food was ambiguous between direct dependence and conditional independence (given CS1). If rats learnt that food was conditionally independent of CS2, given CS1, subjects of both groups should thereafter respond similarly to CS2 alone. Contrary to the conditionality hypothesis, subjects attended to the direct food predictability of CS2, suggesting that rats treat even distal stimuli in a CS sequence as immediately relevant to food, not conditional on an intermediate stimulus. These results urge caution in representing indirect associations as conditional associations, accentuate the theoretical weight of the Markov condition in graphical models, and challenge theories to articulate the conditions under which animals are expected to learn conditional associations, if ever. PMID:28386451

  20. Pathophysiology of the Belgrade rat

    PubMed Central

    Veuthey, Tania; Wessling-Resnick, Marianne

    2014-01-01

    The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis. PMID:24795636

  1. Sorafenib inhibits liver regeneration in rats

    PubMed Central

    Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Sasanuma, Hideki; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Ladekarl, Morten; Mortensen, Frank Viborg

    2013-01-01

    Background Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated. Methods Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling. Results Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8. Conclusion In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation. PMID:23461776

  2. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  3. Spatial Memory in Rats after 25 Hours

    ERIC Educational Resources Information Center

    Crystal, Jonathon D.; Babb, Stephanie J.

    2008-01-01

    We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and…

  4. Same-Different Categorization in Rats

    ERIC Educational Resources Information Center

    Wasserman, Edward A.; Castro, Leyre; Freeman, John H.

    2012-01-01

    Same-different categorization is a fundamental feat of human cognition. Although birds and nonhuman primates readily learn same-different discriminations and successfully transfer them to novel stimuli, no such demonstration exists for rats. Using a spatial discrimination learning task, we show that rats can both learn to discriminate arrays of…

  5. The rat cortex in stereotaxic coordinates.

    PubMed

    Schober, W

    1986-01-01

    On the basis of Nissl-preparations the cortex of albino rats has been mapped cytoarchitectonically. 13 frontal sections through the cortex are illustrated with coordinates. Therewith exists a stereotaxic atlas of the cortex of the rat and one can realize exactly experimental investigations in the different cortical areas.

  6. Anticariogenic effects of tea in rats.

    PubMed

    Rosen, S; Elvin-Lewis, M; Beck, F M; Beck, E X

    1984-05-01

    Teas varying in fluoride and tannin concentration were evaluated in rats for anticariogenic activity. There was a direct correlation between fluoride in tea and the inhibition of sulcal caries in rats, whereas no relationship was observed between tannin and this type of lesion. Teas also had a significant effect on caries progression and imparted a black stain to the teeth.

  7. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.

  8. Experimental oxalate urolith formation in rats.

    PubMed

    McIntosh, G H; Belling, G B; Bulman, F H

    1979-06-01

    Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.

  9. Social exclusion intensifies anxiety-like behavior in adolescent rats.

    PubMed

    Lee, Hyunchan; Noh, Jihyun

    2015-05-01

    Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration.

  10. Identity Matching-to-Sample with Olfactory Stimuli in Rats

    ERIC Educational Resources Information Center

    Pena, Tracy; Pitts, Raymond C.; Galizio, Mark

    2006-01-01

    Identity matching-to-sample has been difficult to demonstrate in rats, but most studies have used visual stimuli. There is evidence that rats can acquire complex forms of olfactory stimulus control, and the present study explored the possibility that identity matching might be facilitated in rats if olfactory stimuli were used. Four rats were…

  11. Rat Control Lesson Plan for Fourth, Fifth and Sixth Grades.

    ERIC Educational Resources Information Center

    Media Learning Corp., Rochester, NY.

    This teacher guide was developed to assist teachers of elementary children in their preparation to teach some lessons on rat control. The overall objectives include determining the level of student understanding about rats, developing student attitudes toward rats, developing the student's ability to identify the rat's weapons, identifying those…

  12. Is fructose sweeter than glucose for rats?

    PubMed

    Ramirez, I

    1996-11-01

    Because it is generally thought that the intensity of the taste of fructose is greater than that of glucose for rats, it seemed surprising when sham-fed rats drank substantially less of a mixture of 6% fructose plus saccharin than of a mixture of 6% glucose plus saccharin. At least 3 different factors contribute to this effect. First, the taste of fructose is less attractive to rats than is the taste of glucose; sham-fed rats strongly preferred glucose over fructose (no saccharin was used in this experiment). The second factor is experience. Rats having substantial previous experience with glucose, but not with fructose, consistently preferred glucose over fructose. Conversely, rats having substantial previous experience with fructose, but not with glucose, initially showed no consistent preference but subsequently tended to prefer glucose. The third factor is an interaction between saccharin and the type of sugar. Rats given only one solution at a time drink approximately as much fructose as glucose when the solutions contain no saccharin. The addition of 0.25% saccharin to 6% glucose stimulated intake, whereas the addition of the same amount of saccharin to 6% fructose did not stimulate intake. As a result, rats ingested substantially more of a mixture of 0.25% saccharin plus 6% glucose than they did of a comparable mixture of saccharin and fructose, even though rats ingest similar amounts of fructose and glucose without saccharin in single-bottle tests. Because the differential effect of saccharin on intake appeared within 2 h in naive rats, and did not greatly change over a 3-day period, it is probably not attributable to conditioning. These results suggest that these sugars have qualitatively different tastes.

  13. Mitochondrial DNA Phylogeography of the Norway Rat

    PubMed Central

    Song, Ying; Lan, Zhenjiang; Kohn, Michael H.

    2014-01-01

    Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus) have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as ∼1.2–1.6 million years ago (Mya), molecular analyses yielded ∼0.5–2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China ∼1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance. PMID:24586325

  14. Mitochondrial DNA phylogeography of the Norway rat.

    PubMed

    Song, Ying; Lan, Zhenjiang; Kohn, Michael H

    2014-01-01

    Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus) have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as ∼ 1.2-1.6 million years ago (Mya), molecular analyses yielded ∼ 0.5-2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China ∼ 1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance.

  15. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    PubMed

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  16. Naturally occurring anti-tissue antibodies in rat sera

    PubMed Central

    Weir, D. M.; Pinckard, R. N.; Elson, C. J.; Suckling, Deirdre E.

    1966-01-01

    Seventy per cent of normal rat sera have been shown to contain heat labile serum component(s) active against various rat organ homogenates as demonstrated by haemolytic complement fixation and passive haemagglutination tests. The main antigenic activity in rat liver has been found in the mitochondrial fractions. It was also demonstrated by the indirect fluorescent antibody technique that both guinea-pig complement and high molecular weight rat globulins were fixed to rat organ sections. Chemotactic activity has also been observed with rat serum and rat liver mitochondria and it is suggested that these naturally occurring antibodies may be implicated in the removal of tissue breakdown products. PMID:5338951

  17. Hepatotoxicity of acetaldehyde in rats.

    PubMed

    Strubelt, O; Younes, M; Urch, T; Breining, H; Pentz, R

    1987-11-01

    The ability of acetaldehyde to initiate hepatotoxicity as evidenced by enzyme leakage, hepatic fat accumulation and histological alterations was studied in rats. Neither oral nor intraperitoneal treatment with acetaldehyde had any hepatotoxic effect, even following aldehyde dehydrogenase inhibition by disulfiram. This is probably due to the inability of exogenously added acetaldehyde to penetrate liver cell membranes. In contrast, acetaldehyde derived metabolically from ethanol was capable of inducing moderate hepatotoxicity when it accumulated upon pretreatment with disulfiram. Acetaldehyde may thus be partly responsible for alcohol-induced liver damage.

  18. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  19. Electroencephalographic changes in albino rats subjected to stress

    NASA Technical Reports Server (NTRS)

    Mercier, J.; Assouline, G.; Fondarai, J.

    1980-01-01

    Twenty one albino Wistar rats were subjected to stress for 7 hours. There was a significant difference in the slopes of regression lines for 7 nonulcerous rats and those for 14 ulcerous rats. Nonulcerous rats subjected to stress showed greater EEG curve synchronization than did ulcerous rats. If curve synchronization can be equated to a relaxed state, it may therefore be possible to explain the protective action of hypnotics, tranquilizers and analgesics on ulcers.

  20. Analysis of vkorc1 polymorphisms in Norway rats using the roof rat as outgroup

    PubMed Central

    2010-01-01

    Background Certain mutations in the vitamin K epoxide reductase subcomponent 1 gene (vkorc1) mediate rodent resistance to warfarin and other anticoagulants. Testing for resistance often involves analysis of the vkorc1. However, a genetic test for the roof rat (Rattus rattus) has yet to be developed. Moreover, an available roof rat vkorc1 sequence would enable species identification based on vkorc1 sequence and the evaluation of natural selection on particular vkorc1 polymorphisms in the Norway rat (R. norvegicus). Results We report the coding sequence, introns and 5' and 3' termini for the vkorc1 gene of roof rats (R. r. alexandrinus and R. r. frugivorus) from Uganda, Africa. Newly designed PCR primers now enable genetic testing of the roof rat and Norway rat. Only synonymous and noncoding polymorphisms were found in roof rats from Uganda. Both nominal subspecies of roof rats were indistinguishable from each other but were distinct from R. losea and R. flavipectus; however, the roof rat also shares at least three coding sequence polymorphisms with R. losea and R. flavipectus. Many of recently published vkorc1 synonymous and non-synonymous single nucleotide polymorphisms (SNPs) in Norway rats are likely SNPs from roof rats and/or other Rattus species. Tests applied to presumably genuine Norway rat vkorc1 SNPs are consistent with a role for selection in two populations carrying the derived Phe63Cys and Tyr139Cys mutations. Conclusion Geographic mapping of vkorc1 SNPs in roof rats should be facilitated by our report. Our assay should be applicable to most species of Rattus, which are intermediate in genetic distance from roof and Norway rats. Vkorc1-mediated resistance due to non-synonymous coding SNPs is not segregating in roof rats from Uganda. By using the roof rat sequence as a reference vkorc1, SNPs now can be assigned to the correct rat species with more confidence. Sampling designs and genotyping strategies employed so far have helped detect candidate mutations

  1. Carbohydrate-conditioned odor preferences in rats.

    PubMed

    Lucas, F; Sclafani, A

    1995-06-01

    The effectiveness of odor cues to support nutrient-conditioned flavor preferences in rats was studied. When the rats drank fluid, the CS+ odor was paired with intragastric (IG) infusions of Polycose, and the CS- odor with IG water. In Experiment 1, rats trained with almond and anise odors presented with plain drinking water failed to acquire a CS+ odor preference. In contrast, rats in Experiment 2 formed a strong aversion to anise (or almond) paired with lithium chloride, which indicated that the odors were distinguishable to the rats. Experiment 3 showed that providing unique tastes (bitter or sour) in combination with the odors during training potentiated odor conditioning. The rats displayed a strong preference for the odor+taste CS+ and for the odor component alone. Experiment 4 showed that with another pair of odor (peppermint and vanilla), CS+ preferences could be conditioned in the absence of taste cues during training. These results demonstrate that rats can acquire strong nutrient-conditioned odor preferences.

  2. Cardiac lesions in rats fed rapeseed oils.

    PubMed Central

    Charlton, K M; Corner, A H; Davey, K; Kramer, J K; Mahadevan, S; Sauer, F D

    1975-01-01

    Fully refined rapeseed oils containing different amounts of erucic acid (1.6%, 4.3% and 22.3%) were fed, at 20% by weight of diet, to weanling male and female Sprague-Dawley rats for periods up to 112 days. Transient myocardial lipidosis characterized by accumulation of fat droplets in myocardial fibers was marked in male and female rats fed oxidized and unoxidized rapeseed oil containing 22.3% erucic acid, moderate with rapeseed oil containing 4.3% erucic acid and very slight in rats fed rapeseed oil containing 1.6% erucic acid. Peak intensity of myocardial lipidosis occurred at three to seven days and regressed thereafter. Focal myocardial necrosis and fibrosis occurred in male rats fed rapeseed oils containing different levels of erucic acid for 112 days. The incidence of myocardial necrosis and fibrosis was markedly lower in female rats, and the incidence of these lesions in either sex was not affected by the state of oxidation of these oils. In a second experiment, male rats were fed diets containing crude, partially refined or fully refined rapeseed oils. There was no correlation between the number of foci of myocardial necrosis and fibrosis and the state of refinement of the oils, but there were generally fewer lesions in rats fed those oils having the lowest levels of erucic acid. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:1170010

  3. Grapefruit juice modulates bone quality in rats.

    PubMed

    Deyhim, Farzad; Mandadi, Kranthi; Faraji, Bahram; Patil, Bhimanagouda S

    2008-03-01

    Hypogonadism and oxidative stress increase the risk for developing osteoporosis. The objective of this research was to evaluate the efficacy of drinking grapefruit juice on bone quality in orchidectomized (ORX) and non-ORX rats. Fifty-six 90-day-old male Sprague-Dawley rats were equally divided into four groups--non-ORX rats (sham), sham + grapefruit juice, ORX, and ORX + grapefruit juice--and treated for 60 days. Thereafter, all rats were sacrificed to determine the plasma antioxidant status, insulin-like growth factor I (IGF-I), and indices of bone turnover, bone quality, and calcium and magnesium concentrations in the bone, urine, and feces. Orchidectomy decreased (P < .05) antioxidant status, bone quality, and bone mineral contents and increased (P < .05) indices of bone turnover, urinary deoxypridinoline, calcium, and magnesium, and fecal calcium excretions. In contrast to the ORX group, ORX rats that drank grapefruit juice had an increase (P < .05) in antioxidant status, bone density, and bone mineral contents, delayed femoral fracture, and slowed down (P < .05) bone turnover rate and tended to have a decrease (P = .08) in urinary deoxypridinoline. In sham-treated animals, drinking grapefruit juice increased (P < .05) bone density and tended to increase the femoral strength. The concentration of IGF-I in the plasma was not affected across treatments. In conclusion, drinking grapefruit juice positively affected bone quality by enhancing bone mineral deposition in ORX rats and by improving bone density in non-ORX rats via an undefined mechanism.

  4. Total parenteral nutrition in diabetic rats

    SciTech Connect

    Norcross, E.D.; Stein, T.P.

    1986-03-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using /sup 15/N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats.

  5. Photoperiodic response in the male laboratory rat.

    PubMed

    Wallen, E P; DeRosch, M A; Thebert, A; Losee-Olson, S; Turek, F W

    1987-08-01

    Normally photoperiodic laboratory rats can be induced to respond reproductively to a change in the length of the day by various experimental manipulations. One such paradigm that results in significant gonadal regression involves the treatment of rats with exogenous testosterone during exposure to short days. Studies were undertaken to assess various aspects of this model system including 1) the testicular response of testosterone-treated rats exposed to various photoperiods, 2) the time course for testicular regression under a short photoperiod, and 3) the role of the pineal gland as a mediator of the effects of day length on the neuroendocrine-gonadal axis. Photoperiods ranging in length from 2 to 22 h/24 h had no effect on testicular size in untreated rats. In contrast, while near normal testicular weights were maintained in laboratory rats treated with testosterone and exposed to 10 or more h of light per day, testicular regression occurred in rats implanted with testosterone-filled capsules and exposed to photoperiods of 8 or fewer h of light per day. Maximal testicular regression was reached in about 9 wk in testosterone-treated rats exposed to 6L:18D. Removal of the pineal gland totally blocked the inhibitory effects of exposure to short day lengths in testosterone-treated rats. These studies define some of the characteristics of an extant, but dormant, system for photoperiodic time measurement in the common laboratory rat and implicate a role for the pineal gland in this system. These experiments offer evidence that neuroendocrine factors that regulate continuous vs. seasonal reproductive patterns are malleable. Such flexibility in the photoperiodic response may also contribute to the evolution of seasonal to non-seasonal species and vice versa.

  6. Antidepressant effect of taurine in diabetic rats.

    PubMed

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  7. Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

    PubMed

    Díaz-Morán, Sira; Palència, Marta; Mont-Cardona, Carme; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; López-Aumatell, Regina; Tobeña, Adolf; Fernández-Teruel, Alberto

    2012-03-01

    The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

  8. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.

  9. Origins of blood acetate in the rat.

    PubMed Central

    Buckley, B M; Williamson, D H

    1977-01-01

    A novel enzymimc cycling assay for the determination of acetate in biological material is described. Measurements of the acetate concentration in blood and liver samples from rats of various ages and nutritional states with this assay are reported. The contribution of the intestine, the liver and the rest of the body to maintaining the concentration of acetate in the circulation is examined. Evidence is presented that the gut flora constitute the main source of acetate in blood of fed adult rats, though endogenous production of acetate is of significance in other situations. The streptozotocin-diabetic rat has an elevated blood acetate concentration. PMID:597244

  10. Hypothalamic thermosensitivity in capsaicin-desensitized rats.

    PubMed Central

    Cormarèche-Leydier, M; Shimada, S G; Stitt, J T

    1985-01-01

    In rats, we tested the hypothesis that capsaicin desensitization reduces hypothalamic warm thermosensitivity. We locally heated and cooled the hypothalamus using water-perfused thermodes while observing thermoregulatory variables. In untreated rats, a small dose of capsaicin had profound effects on thermoregulation. However, desensitizing rats to capsaicin had no effect on hypothalamic thermosensitivity for metabolic rate or changes in body temperature due to displacements of hypothalamic temperature. Contrary to current opinion, we conclude that capsaicin desensitization does not alter hypothalamic thermosensitivity to warm or cold. PMID:4020699

  11. Malignant neoplasms in rats fed lasiocarpine.

    PubMed Central

    Rao, M. S.; Reddy, J. K.

    1978-01-01

    Lasiocarpine, a pyrrolizidine alkaloid, was fed at a dietary concentration of 50/10(6) for 55 weeks, to 20 male F-344 rats. Malignant tumours developed in 17/20 animals between 48 and 59 weeks. Forty-five percent (9/20) developed angiosarcomas of the liver and 35% (7/20) had hepatocellular carcinomas. Other tumours included malignant adnexas tumour of the skin (1 rat) and lympohoma (1 rat). Lung metastases were observed in 4 animals with angiosarcoma of the liver and one animal with hepatocellular carcinoma. From one animal, angiosarcoma was successfully transplanted through 4 generations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:204322

  12. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    PubMed

    Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

    2015-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

  13. Derivation of embryonic stem cells from Brown Norway rats blastocysts.

    PubMed

    Zhao, Xiaoyang; Lv, Zhuo; Liu, Lei; Wang, Liu; Tong, Man; Zhou, Qi

    2010-07-01

    Knockout Brown Norway (BN) rat could be a useful disease model for human disorders, however, a failure to derive embryonic stem (ES) cells disturbs the further development of the model. In this study, we reported a case of successful derivation of the BN rat ES cells with the derivation efficiency comparable to that of Sprague Dawley (SD) rats. The BN rat ES cells expressed the key transcription factors, and were able to form embryonic bodies (EBs) when being differentiated in vitro. After injecting the BN rat ES cells into the SD rat blastocysts, high-contribution chimeric rats were generated and could survive to their adulthood. Our success in generating pluripotent rat ES cells will benefit the generation of the knockout rats in the future.

  14. Milk composition of rats feeding restricted litters.

    PubMed Central

    Grigor, M R; Allan, J; Carne, A; Carrington, J M; Geursen, A

    1986-01-01

    Milk samples were taken from rats feeding ten pups and from both the suckled and non-suckled glands of rats feeding two pups. The lipid, protein and lactose concentrations were similar in the milks from the secreting glands, but the fluid from the non-suckled glands contained less lactose and lipid but significantly higher total protein and transferrin concentrations. The fatty acid compositions of the milk from the three sources were very similar. The mammary tissue from the rats feeding ten pups had a higher DNA content/g wet wt. than either the suckled or non-suckled mammary tissue of the rats feeding two pups. The specific activities of several lipogenic enzymes were significantly lower in the non-suckled mammary tissue. PMID:3707536

  15. Hypergravity induced prolactin surge in female rats

    NASA Technical Reports Server (NTRS)

    Megory, E.; Oyama, J.

    1985-01-01

    Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

  16. Corona Discharge Influences Ozone Concentrations Near Rats

    SciTech Connect

    Goheen, Steven C.; Gaither, Kari A.; Anantatmula, Shantha M.; Mong, Gary M.; Sasser, Lyle B.; Lessor, Delbert L.

    2004-02-26

    Ozone is produced by corona discharge in air. Its production is enhanced near grounded water. Whether grounded animals behave like grounded water, producing more ozone was investigated. Rats were exposed to corona discharge in a plastic cage. The concentration of ozone in the gas phase was monitored. The ozone concentration exceeded ambient levels only in the presence of corona discharge and either rats or water. When water or rats were exposed to corona discharge, ozone levels were more than 10 times higher than controls. Ozone levels increased rapidly with applied voltage. There was also a correlation between the distance of the corona needle to the rats and the amount of ozone produced. As the distance increased, ozone production decreased. These results are discussed in relation to the potential exposure of mammals to ozone in the vicinity of corona discharge and electric fields.

  17. 2011 Desert RATS Sights and Sounds

    NASA Video Gallery

    Watch scenes from the 2011 Desert Research and Technology Studies (RATS) analog field test, as NASA scientists and engineers drive the Space Exploration Vehicle, assemble equipment in the Habitat D...

  18. Rat Bite Fever Resembling Rheumatoid Arthritis

    PubMed Central

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  19. Rat sperm motility analysis: methodologic considerations

    EPA Science Inventory

    The objective of these studies was to optimize conditions for computer-assisted sperm analysis (CASA) of rat epididymal spermatozoa. Methodologic issues addressed include sample collection technique, sampling region within the epididymis, type of diluent medium used, and sample c...

  20. How rats combine temporal cues.

    PubMed

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  1. Thyroid function in hemidecorticate rats.

    PubMed

    Munhoz, C O; Tosello, D O; Fernandez, G A; Merzel, J

    1988-01-01

    1. Thyroid function was evaluated in hemidecorticate (HD) and control (C) rats by determining serum T3 and T4 levels and the development of incisors and mandibles and through analysis of various histological features of the thyroid such as follicle size, colloid droplet content and [3H]-glycine uptake by follicular cells. 2. HD animals presented normal levels of circulating T3 but significantly lower T4 levels. 3. There was slight atrophy of the gland in HD animals and fewer colloid droplets were present in the cytoplasm of the follicular cells in this group, indicating a reduction in the breakdown of thyroglobulin. [3H]-glycine uptake by HD indicated that the rate of thyroglobulin biosynthesis was not altered in the experimental animals. 4. The growth of mandibles (weight) and incisors (weight and length) was reduced in HD compared to the control animals. 5. These results suggest that hemidecortication causes mild hypothyroidism (trophoprivic type) probably by affecting hypothalamic function.

  2. The rat brain hippocampus proteome.

    PubMed

    Fountoulakis, Michael; Tsangaris, George T; Maris, Antony; Lubec, Gert

    2005-05-05

    The hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In humans, the CA1 area of hippocampus is one of the first brain areas to display pathology in Alzheimer's disease. A comprehensive analysis of the hippocampus proteome has not been accomplished yet. We applied proteomics technologies to construct a two-dimensional database for rat brain hippocampus proteins. Hippocampus samples from eight months old animals were analyzed by two-dimensional electrophoresis and the proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The database comprises 148 different gene products, which are in the majority enzymes, structural proteins and heat shock proteins. It also includes 39 neuron specific gene products. The database may be useful in animal model studies of neurological disorders.

  3. Neptunium-237 inhalation in rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Buschbom, R L

    1986-12-01

    Groups of rats were exposed to aerosols of 237Np nitrate to determine clearance rates, retention and distribution at various intervals after inhalation. Initial lung burdens (ILB) after 237Np inhalation by three treatment groups were 0.12, 0.19 and 0.37 mu Ci/kg, respectively. Radiochemical analyses of animals killed at 4, 8, 14, 28 and 90 d, as well as data for others maintained until they became moribund, showed that their lung clearance followed a three-compartment model, clearance half-times for which were 1, 35, and 10,000 d, respectively. Only 3% of the ILB was retained after 90 d; 12% of that burden had translocated to the skeleton at 750 d; the half-time for skeletal retention was 2500 d. A single tumor was the only malignancy detected in the lungs of the 35 animals allowed to survive the early phase of the study.

  4. Rat growth during chronic centrifugation

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Oyama, J.

    1978-01-01

    Female weanling rats were chronically centrifuged at 4.15 G with controls at terrestrial gravity. Samples were sacrificed for body composition studies at 0, 28, 63, 105 and 308 days of centrifugation. The centrifuged group approached a significantly lower mature body mass than the controls (251 and 318g) but the rate of approach was the same in both groups. Retirement to 1G on the 60th day resulted in complete recovery. Among individual components muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.

  5. Can You Find the Rat Holes?

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Using its rock abrasion tool, otherwise known as 'Rat,' NASA's Mars Exploration Rover Opportunity dotted the slope of 'Endurance Crater' with dimples that give scientists a glimpse into its layered geologic history. This image from the rover's navigation camera, taken on sol 169 (July 15, 2004), highlights the prolific work of the robotic 'rodent.' How many Rat holes can you identify? You will be able to check your answer against an image to be posted soon with all the holes identified.

  6. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    DTIC Science & Technology

    1991-12-01

    during aggression in rats and some other myomorph species (e.g., Acomys cahirinus, Apcdemus sylvati- cus). Other species (e.g., MusM muau_...which occur when the young are handled. The author reports that, unlike rats, other rodent species (e.g., lab mice, Acomys cahirinus, Clethrionomys gajj... Acomys was removed from the mother’s cage, and during exploratory behavior in Apodemus gyiL vaticus. i1 Sewell, G.D. Ultrasonic signals from rodents

  7. Quantity Discrimination in Domestic Rats, Rattus norvegicus

    PubMed Central

    Cox, Laura; Montrose, V. Tamara

    2016-01-01

    Simple Summary Quantity discrimination involves distinguishing which of two quantities is greater. This discrimination between larger and smaller quantities has only been demonstrated in rats post extensive training. We tested whether domestic rats could perform quantity discrimination without explicit training. We found that rats could distinguish the greater amount in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. Rats could not distinguish between 3 vs. 4, 4 vs. 5 and 5 vs. 6. We also found that as the ratio between quantities became finer the choice of the larger quantity decreased. We conclude that rats can perform quantity discrimination without extensive training and that their quantity discrimination ability is influenced by the ratio between quantities. Abstract Quantity discrimination is a basic form of numerical competence where an animal distinguishes which of two amounts is greater in size. Whilst quantity discrimination in rats has been investigated via training paradigms, rats’ natural quantity discrimination abilities without explicit training for a desired response have not been explored. This study investigated domestic rats’ ability to perform quantity discrimination. Domestic rats (n = 12) were examined for their ability to distinguish the larger amount under nine quantity comparisons. One-sample t-tests identified a significant preference for the larger quantity in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. No preference between quantities was found for comparisons of 3 vs. 4, 4 vs. 5 and 5 vs. 6. Overall, this study drew two key conclusions. Firstly, that domestic rats are capable of performing quantity discrimination without extensive training. Secondly, as subjects adhered to Weber’s law, it was concluded that the approximate number system underpins domestic rats’ ability to perform spontaneous quantity discrimination. PMID:27527223

  8. A digital rat atlas of sectional anatomy

    NASA Astrophysics Data System (ADS)

    Yu, Li; Liu, Qian; Bai, Xueling; Liao, Yinping; Luo, Qingming; Gong, Hui

    2006-09-01

    This paper describes a digital rat alias of sectional anatomy made by milling. Two healthy Sprague-Dawley (SD) rat weighing 160-180 g were used for the generation of this atlas. The rats were depilated completely, then euthanized by Co II. One was via vascular perfusion, the other was directly frozen at -85 °C over 24 hour. After that, the frozen specimens were transferred into iron molds for embedding. A 3% gelatin solution colored blue was used to fill the molds and then frozen at -85 °C for one or two days. The frozen specimen-blocks were subsequently sectioned on the cryosection-milling machine in a plane oriented approximately transverse to the long axis of the body. The surface of specimen-blocks were imaged by a scanner and digitalized into 4,600 x2,580 x 24 bit array through a computer. Finally 9,475 sectional images (arterial vessel were not perfused) and 1,646 sectional images (arterial vessel were perfused) were captured, which made the volume of the digital atlas up to 369.35 Gbyte. This digital rat atlas is aimed at the whole rat and the rat arterial vessels are also presented. We have reconstructed this atlas. The information from the two-dimensional (2-D) images of serial sections and three-dimensional (3-D) surface model all shows that the digital rat atlas we constructed is high quality. This work lays the foundation for a deeper study of digital rat.

  9. Hindlimb unweighting affects rat vascular capacitance function

    NASA Technical Reports Server (NTRS)

    Dunbar, S. L.; Tamhidi, L.; Berkowitz, D. E.; Shoukas, A. A.

    2001-01-01

    Microgravity is associated with an impaired stroke volume and, therefore, cardiac output response to orthostatic stress. We hypothesized that a decreased venous filling pressure due to increased venous compliance may be an important contributing factor in this response. We used a constant flow, constant right atrial pressure cardiopulmonary bypass procedure to measure total systemic vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These compliance values were calculated under baseline conditions and during an infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in reservoir volume, which reflects changes in unstressed vascular volume (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V) were larger in HLU rats both at baseline and during the NE infusion (P < 0.05). Infusion of NE decreased C(T) and C(V) by 20% in both HLU and control rats (P < 0.01). C(A) was also significantly decreased in both groups of rats by NE (P < 0.01), but values of C(A) were similar between HLU and control rats both at baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling pressure during orthostasis and thus may partially underlie the mechanism leading to the exaggerated fall in stroke volume and cardiac output seen in astronauts during an orthostatic stress after exposure to microgravity.

  10. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  11. Interpretation of male rat renal tubule tumors.

    PubMed Central

    Rodgers, I S; Baetcke, K P

    1993-01-01

    Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency's (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of alpha 2u-globulin (alpha 2u-g), a low molecular weight protein, in the male rat kidney. The alpha 2u-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving alpha 2u-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. PMID:7517352

  12. Oxalate metabolism in magnesium-deficient rats.

    PubMed

    Rattan, V; Thind, S K; Jethi, R K; Sidhu, H; Nath, R

    1993-06-01

    Male weanling rats were maintained on magnesium-deficient diet for 30 d and compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium deficiency led to slow growth and finally to a significant decrease in body weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to the control rats. Magnesium deficiency altered the glyoxylate metabolism in the liver and kidney mitochondria by significantly decreasing glyoxylate oxidation (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha-ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per cent in kidney) in the experimental animals. A significant increase in the specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P < 0.01) was also observed in magnesium-deficient rats. No change in liver and kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats leads to accumulation of glyoxylate in the tissues, a part of which is converted into oxalate, thereby promoting hyperoxaluria.

  13. Sexually Dimorphic Risk Mitigation Strategies in Rats

    PubMed Central

    Pellman, Blake A.; Schuessler, Bryan P.

    2017-01-01

    Abstract The scientific understanding of fear and anxiety—in both normal and pathological forms—is presently limited by a predominance of studies that use male animals and Pavlovian fear conditioning-centered paradigms that restrict and assess specific behaviors (e.g., freezing) over brief sampling periods and overlook the broader contributions of the spatiotemporal context to an animal’s behavioral responses to threats. Here, we use a risky “closed economy” system, in which the need to acquire food and water and the need to avoid threats are simultaneously integrated into the lives of rats, to examine sex differences in mitigating threat risk while foraging. Rats lived for an extended period (∼2 months) in enlarged chambers that consisted of a safe, bedded nest and a risky foraging area where footshocks could be delivered unpredictably. We observed that male and female rats used different strategies for responding to the threat of footshock. Whereas male rats increased the size of meals consumed to reduce the overall time spent foraging, female rats sacrificed their metabolic needs in order to avoid shocks. Ovarian hormone fluctuations were shown to exert slight but reliable rhythmic effects on risky decision-making in gonadally intact female rats. However, this did not produce significant differences in approach–avoidance trade-offs between ovariectomized and intact female groups, suggesting that male–female sex differences are not due to the activational effects of gonadal hormones but, rather, are likely to be organized during early development. PMID:28197550

  14. Colonic Fermentation Promotes Decompression sickness in Rats

    PubMed Central

    de Maistre, Sébastien; Vallée, Nicolas; Gempp, Emmanuel; Lambrechts, Kate; Louge, Pierre; Duchamp, Claude; Blatteau, Jean-Eric

    2016-01-01

    Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body’s H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production. PMID:26853722

  15. Hypergravity modulates behavioral nociceptive responses in rats

    NASA Astrophysics Data System (ADS)

    Kumei, Y.; Shimokawa, R.; Toda, K.; Kawauchi, Y.; Makita, K.; Terasawa, M.; Ohya, K.; Shimokawa, H.

    Hypergravity (2G) exposure elevated the nociceptive threshold (pain suppression) concomitantly with evoked neuronal activity in the hypothalamus. Young Wistar male rats were exposed to 2G by centrifugal rotation for 10 min. Before and after 2G exposure, the nociceptive threshold was measured as the withdrawal reflex by using the von Frey type needle at a total of 8 sites of each rat (nose, four quarters, upper and lower back, tail), and then rats were sacrificed. Fos expression was examined immunohistochemically in the hypothalamic slices of the 2G-treated rats. When rats were exposed to 2G hypergravity, the nociceptive threshold was significantly elevated to approximately 150 to 250% of the 1G baseline control levels in all the examination sites. The 2G hypergravity remarkably induced Fos expression in the paraventricular and arcuate nuclei of the hypothalamus. The analgesic effects of 2G hypergravity were attenuated by naloxone pretreatment. Data indicate that hypergravity induces analgesic effects in rats, mediated through hypothalamic neuronal activity in the endogenous opioid system and hypothalamo-pituitary-adrenal axis.

  16. Interaction between corticosterone and insulin in obesity: regulation of lard intake and fat stores.

    PubMed

    la Fleur, Susanne E; Akana, Susan F; Manalo, Sotara L; Dallman, Mary F

    2004-05-01

    Passive elevations in glucocorticoids result in increased insulin and abdominal obesity with peripheral wasting, as observed in Cushing's syndrome, with little effect on chow intake. In the absence of insulin (streptozotocin-induced diabetes) diabetic rats markedly increase their chow intake in proportion to glucocorticoids. Given a choice of lard or chow, diabetic rats first eat lard, then reduce caloric intake to normal for 48 h before returning to hyperphagia on chow alone. We performed three experiments to determine the relationship of corticosterone and insulin to lard intake, chow intake, body weight, hormones, and fat depots. The results of these studies clarify the actions of both circulating glucocorticoids and insulin on caloric intake in adult male rats. Our experiments show that glucocorticoids provoke dose-related increases in total caloric intake that persist for days and weeks; the results also suggest that increasing insulin concentrations stimulated by glucocorticoids determine the amount of fat intake. Furthermore, we show that lard intake is associated with increasing insulin concentrations. Additionally, the results in adrenalectomized and adrenalectomized, streptozotocin-induced diabetic rats strongly suggest that it is a combination of corticosterone and insulin that increases abdominal fat depot weight. Independently of the hormonally manipulated rats, the results also show that intact rats voluntarily eat a considerable and stable proportion of their daily calories as lard when given a choice between lard and chow. These results suggest that some human obesities may result from elevated glucocorticoids and insulin increasing the proportional intake of high density calories.

  17. Transient dehydration of lungs in tail-suspended rats

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Steskal, J.; Morey-Holton, E. R.

    1985-01-01

    The fluid balance in the lungs of rats exposed to head-down tilt is examined. Six Munich-Wister rats were suspended for 7 days and 10 Sprague-Dawley rats for 14 days using the technique of Morey (1979). The water contents of the lungs of the suspended and a control group are calculated and compared. The data reveal that the two-days suspended rats had dehydrated lungs; however, the lungs of the 14-day suspended and control group rats were similar. It is noted that the dehydration in the 2-day suspended rats is caused by general dehydration not the head-tilt position.

  18. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  19. Effects of BCL-2 over-expression on B cells in transgenic rats and rat hybridomas.

    PubMed

    Iscache, Anne-Laure; Ménoret, Séverine; Tesson, Laurent; Rémy, Séverine; Usal, Claire; Pedros, Christophe; Saoudi, Abdelhadi; Buelow, Roland; Anegon, Ignacio

    2011-10-01

    The rat is an important biomedical experimental model that benefited from the recent development of new transgenic and knockout techniques. With the goal to optimize rat mAb production and to analyze the impact of Bcl-2 on B-cell development, we generated bcl-2 transgenic rats. Transgenic rats showed Bcl-2 over-expression in B cells, increased B cell numbers in lymphoid organs, elevated production of immunoglobulins (Igs) and prolonged B-cell survival in vitro. Transgenic rats remained healthy, reproduced normally and did not develop autoimmunity. Fusions with bcl-2 transgenic splenocytes did not result in increased hybridoma generation. A comparison of on- and off-rates of 39 mAbs generated with bcl-2 transgenic and wild-type animals revealed no significant differences. Over-expression of Bcl-2 in hybridomas did not change cell proliferation but resulted in increased Ig production. Bcl-2 transgenic rats will be a useful tool for the generation of rat mAbs, the analysis of B cells in different pathophysiological models, such as autoimmunity, cancer or organ transplantation, and the study of rat B-cell biology.

  20. Endothelial dysfunction in cold-induced hypertensive rats.

    PubMed

    Zhu, Zhiming; Zhu, Shanjun; Zhu, Jijun; van der Giet, Markus; Tepel, Martin

    2002-02-01

    Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion of acetylcholine significantly lowered mean arterial BP in control rats by 48 +/- 2% and by 32 +/- 1% in cold-induced hypertensive rats. The acetylcholine-induced reduction of mean arterial BP was significantly attenuated in cold-induced hypertensive rats (control rats, 45 +/- 2 mm Hg; cold-induced hypertensive rats, 34 +/- 3 mm Hg; P < .05). Administration of N(G)-nitro-L-arginine-methyl ester for 1 week significantly increased BP in control rats, whereas no effect could be observed in cold-induced hypertensive rats. In cold-induced hypertensive rats eNOS in aortic vessels was significantly reduced compared to control rats. In this nongenetic, nonsurgical animal model of cold-induced hypertensive rats an endothelial dysfunction can be observed due to reduced eNOS.

  1. Social Structure Predicts Genital Morphology in African Mole-Rats

    PubMed Central

    Seney, Marianne L.; Kelly, Diane A.; Goldman, Bruce D.; Šumbera, Radim; Forger, Nancy G.

    2009-01-01

    Background African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. Methodology/Principal Findings We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. Conclusions/Significance The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology. PMID:19829697

  2. Rat leucocyte response to the bites of rat fleas (Siphonaptera: Pulicidae).

    PubMed

    Vaughan, J A; Jerse, A E; Azad, A F

    1989-09-01

    The host response to bites of the oriental rat flea, Xenopyslla cheopis Rothschild, was investigated by examining rat blood leucocyte kinetics, histopathology, and the effect that the host response had upon subsequent flea feeding and longevity. Test rats were subjected to controlled exposures of fleas, and leucocyte data from test rats were compared to those of unexposed controls. Of the five leucocyte types examined, only the basophil appeared to play a role in the host blood response to flea bites. Significant increases in blood basophil levels occurred 2-3 d after exposure but subsided to control levels within a week. However, flea feeding did not produce histopathology at the flea feeding sites nor did the basophilic blood response of rats affect subsequent feeding or longevity of the fleas.

  3. Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression.

    PubMed

    Adlard, P A; Cotman, C W

    2004-01-01

    Exercise is increasingly recognized as an intervention that can reduce CNS dysfunctions such as cognitive decline, depression and stress. Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in the hippocampus following exercise. In this study we tested the hypothesis that exercise can counteract a reduction in hippocampal BDNF protein caused by acute immobilization stress. Since BDNF expression is suppressed by corticosterone (CORT), circulating CORT levels were also monitored. In animals subjected to 2 h immobilization stress, CORT was elevated immediately following, and at 1 h after the cessation of stress, but remained unchanged from baseline up to 24 h post-stress. The stress protocol resulted in a reduction in BDNF protein at 5 and 10 h post-stress that returned to baseline at 24 h. To determine if exercise could prevent this stress-induced reduction in BDNF protein, animals were given voluntary access to running wheels for 3 weeks prior to the stress. Stressed animals, in the absence of exercise, again demonstrated an initial elevation in CORT (at 0 h) and a subsequent decrease in hippocampal BDNF at the 10 h time point. Exercising animals, both non-stressed and stressed, demonstrated circulating CORT and hippocampal BDNF protein levels that were significantly elevated above control values at both time points examined (0 and 10 h post-stress). Thus, the persistently high CORT levels in exercised animals did not affect the induction of BDNF with exercise, and the effect of immobilization stress on BDNF protein was overcome. To examine the role of CORT in the stress-related regulation of BDNF protein, experiments were carried out in adrenalectomized (ADX) animals. BDNF protein was not downregulated as a result of immobilization stress in ADX animals, while there continued to be an exercise-induced upregulation of BDNF. This study demonstrates that CORT modulates stress-related alterations in BDNF protein. Further, exercise

  4. Reduced T cell response in carcinogen-sensitive Donryu rats compared with carcinogen-resistant DRH rats.

    PubMed

    Mise-Omata, S; Sugiura, T; Higashi, K; Yamashita, U

    1999-12-01

    Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3'-methyl-4-dimethyl-amino-azobenzene (3'-MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) complex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts to exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats. Flow cytometric analysis revealed that the expression of CD4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These results indicate that Donryu rats, which have been used in many years for cancer research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibility to transplanted tumor cells of Donryu rats.

  5. National BioResource Project-Rat and related activities.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Takizawa, Akiko; Okajima, Ryoko; Maedomari, Naoki; Kumafuji, Kenta; Tagami, Fumi; Neoda, Yuki; Otsuki, Mito; Nakanishi, Satoshi; Yamasaki, Ken-ichi; Voigt, Birger; Kuramoto, Takashi

    2009-07-01

    In order to establish a system to facilitate the systematic collection, preservation, and provision of laboratory rats (Rattus norvegicus) and their derivates, the National BioResource Project-Rat (NBRP-Rat) was launched in July 2002. By the end of 2008, more than 500 rat strains had been collected and preserved as live animals, embryos, or sperm. These rat resources are supplied to biomedical scientists in Japan as well as in other countries. This review article introduces NBRP-Rat and highlights the phenome project, recombinant inbred strains, BAC clone libraries, and the ENU-mutant archive, named the Kyoto University Rat Mutant Archive (KURMA). The future direction of rat resources are also discussed.

  6. Effect of simulated weightlessness on energy metabolism in the rat

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

    Results of measurements of food uptake and body weight changes occurring in rats suspended from a harness so that the antigravity muscles were not used for locomotion are presented. The rats were tested in pairs, with both in a harness but only one suspended off its hind legs; this section lasted 7 days. A second phase of the experiment involved feeding the nonsuspended rat the same amount of food the experimental rat had consumed the previous day. All rats experienced decreased in body weight and food intake in the first stage, while in the second stage the suspended rat lost more weight. The total oxygen uptake, CO2 output, and rate of C-14O2 production were depressed in the suspended rats, then returned to normal levels once the rats were back on the ground. It is concluded that the gross metabolic processes are unaffected by simulated weightlessness.

  7. Expression of oxytocin receptor in diabetic rat penis.

    PubMed

    Li, M; Wang, T; Guo, S; Rao, K; Liu, J; Ye, Z

    2012-05-01

    Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.

  8. High prevalence of rat hepatitis E virus in wild rats in China.

    PubMed

    Li, Wei; Guan, Dawei; Su, Juan; Takeda, Naokazu; Wakita, Takaji; Li, Tian-Cheng; Ke, Chang Wen

    2013-08-30

    Serum samples from a total of 713 wild rats captured in Zhanjiang city in China from December 2011 to September 2012 were investigated for the prevalence of rat hepatitis E virus (HEV) by exploring rat HEV-specific antibodies and RNA. By an ELISA based on recombinant rat HEV-like particles (HEV-LPs), 23.3% (166/713) of the rats were positive for anti-HEV IgG, and 8.3% (59/713) were positive for anti-HEV IgM. The IgG-positive rates in Rattus norvegicus, Bandicota indica, Rattus flavipectus, Rattus rattoides losea, and Rattus rattus hainanus, were 27.8% (64/230), 23.0% (40/174), 19.9% (34/171), 21.5% (26/121), and 11.8% (2/17), while the IgM-positive rates were 8.3% (19/230), 6.9% (12/174), 8.2% (14/171), 10.7% (13/121), and 5.9% (1/17), respectively. The IgG-positive rate of the rats captured in rural areas, 24.1% (84/348), was higher than that in the central area of Zhanjiang city, 15.1% (32/212). The highest IgG-positive rates, as high as 45.3% (39/86), were detected in wild rats trapped in the garbage dump. Twelve of the 59 IgM-positive serum samples were positive for HEV RNA, which was detected in all of the wild rat species except R. rattus hainanus. A phylogenetic analysis of the partial genome of rat HEV ORF1 indicated that all of the 12 HEV strains belong to rat HEV, and no other genotype HEV were detected. The rat HEV from Zhangjiang city could be classified into three separated clusters, suggesting that the infection due to rat HEV with a variety of genome entities occurs extensively among wild rats in China.

  9. The Metabolism of Tetralin in Fischer 344 Rats

    DTIC Science & Technology

    1986-04-01

    would die from the disease. The relevance of nephropathy observed in male rats exposed to various hydrocarbons to the occurrence of renal neoplasia in man...hydrocarbons develop dose-related nephropathies which are not observed in female rats and control rats or in the males and females of other animal...then held for long-term, post-exposure evaluation revealed tubular degeneration consistent with "old-rat nephropathy " (explained below). C. Chronic

  10. Behavioral Toxicological Studies of Pesticides in Laboratory Rats,

    DTIC Science & Technology

    Behavior, *Toxicology, *Pesticides, *Rats, Symposia, Laboratory tests, Toxicity, Insecticides, Exposure( General ), Dosage, Perception, Motor reactions, Learning, Military psychology , Military medicine

  11. Nigella Sativa reverses osteoporosis in ovariectomized rats

    PubMed Central

    2014-01-01

    Background Osteoporosis poses a significant public health issue. It is a skeletal disorder characterized by compromised bone strength that predisposes to increased risk of fracture. There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. About 33% of women over 50 will experience bone fractures as a result of osteoporosis. Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats. Methods Female Wistar rats aged 12–14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. After 12 weeks, plasma levels of calcium (Ca+2), phosphorous (Pi), alkaline phosphatase (ALP), amino terminal collagen type 1 telopeptide, malondialdehyde (MDA), nitrates, nitric oxide surrogate, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Histological examination of the liver and the tibia was conducted. Histomorphometric analysis of the tibia was also performed. Results OVX rats showed significant decrease in plasma Ca+2, accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found

  12. Microdialysis of triamcinolone acetonide in rat muscle.

    PubMed

    Rojas, Cioli; Nagaraja, Nelamangala V; Webb, Alistair I; Derendorf, Hartmut

    2003-02-01

    The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V. bolus 50 mg/kg of the phosphate ester of TA (TAP) followed by 23 mg/kg/h infusion. In vivo recovery was calculated by retrodialysis. The concentration determined at steady state in microdialysate, corrected for recovery, was 2.73 +/- 0.42 microg/mL compared to 21.9 +/- 2.3 microg/mL in plasma. The pharmacokinetics of TA in plasma was described by an open two-compartment model with a terminal half-life of 2.7 h. The clearance of TA in rats determined by compartmental analysis was 0.94 L/h/kg. The measured microdialysate levels of TA in muscle, corrected for recovery, were comparable to the predicted free drug levels in the peripheral compartment. Protein binding in rat plasma, measured by ultrafiltration, was 90.1%. The microdialysis in vivo recovery in muscle was similar to the in vitro recovery under stirred conditions. The results show the applicability of microdialysis to measure free tissue concentrations of TA in rats.

  13. Cardiopulmonary Changes with Moderate Decompression in Rats

    NASA Technical Reports Server (NTRS)

    Robinson, R.; Little, T.; Doursout, M.-F.; Butler, B. D.; Chelly, J. E.

    1996-01-01

    Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

  14. Radioimmunoimaging of pneumocystis carinii infection in rats

    SciTech Connect

    Vallabhajosula, S.; Shane, L.B.; Goldsmith, S.J.; Lipszyc, H.; Walzer, P.

    1984-01-01

    Pneumocystis carinil pneumonia (PCP) is seen in patients with impaired immunity due to chemotherapeutic suppression or to a primary disorder, congenital or AIDS. Although radiogallium imaging has been helpful in the workup of PCP, it is non-specific. Since there is no early specific non-invasive method to diagnose PCP, the authors are developing an imaging technique using radiolabeled antibodies. Fulminant PCP was induced in rats by injecting cortisone, 20mg 2-3 times/wk for 8 wks. PC cells isolated from rat lung were injected into rabbits. The antiserum thus derived was separated and purified using Protein-A bound sepharose column with identification of IgG by polyacrylamide gel electrophoresis. Both rabbit antipneumocystis antibodies and purified IgG(Sigma) were iodinated with I-131 to a high specific activity (3-5..mu..Ci/ug) using a lactoperoxidase method. /sup 131/I-labeled specific and non-specific IgG were injected into rats with PC infection and imaged with an Anger camera. After sacrifice, I-131 activity/gram tissue (lung, liver, heart) was determined and expressed as organ ratios. An increased uptake of specific antibody in lungs of rats with PCP was demonstrated by organ counting and imaging. This increase was not seen in normal controls or rats injected with non-specific IgG. These data provide a basis for radioimmunoimaging of infectious diseases.

  15. The queer life of a lab rat.

    PubMed

    Pettit, Michael

    2012-08-01

    The laboratory rat is an important, if neglected, actor in the history of sexuality. From the 1920s and 1940s, a series of reports emerged from American psychology laboratories detailing instances of spontaneous "reversals" in sexual behavior within their rat colonies. Frank Beach, then at the American Museum of Natural History, developed a model for the "nature" of sexuality that stressed that all organisms had the neurological capacity to perform behavior of either sex. Beach enrolled his emerging specialty, behavioral endocrinology, in support of Alfred Kinsey's controversial findings. Both scientists highlighted the multitude of potential sexual outlets pursued by organisms and the prevalence of nonprocreative sexual behaviors. This article draws on elements of queer theory to elucidate how the landscape of the comparative psychologist's rat colony with its organisms, apparatus, practices, and rituals served an integral function in the redefinition of sex in the 20th century. Queer theory calls into question easy proclamations about what counts as natural or normal by drawing attention to the presumed binaries that frequently govern the classification of sex. The maintenance of the colony required the careful management of sex with its obstruction devices, hypersexualized indicator animals, segregation cages, and castrated rats injected with hormones. Moreover, Beach's own writings indicate how his own domestic life became entangled with the sex lives of the rats. An irony animates this Rockefeller-funded sexology: Research funded to elucidate the mechanisms underlying heterosexuality came to question its innateness and universality. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  16. Immunopathological features of rat Staphylococcus aureus arthritis.

    PubMed Central

    Bremell, T; Lange, S; Holmdahl, R; Rydén, C; Hansson, G K; Tarkowski, A

    1994-01-01

    Staphylococcus aureus is the most common bacterial species found in nongonococcal bacterial arthritis in humans. We present the first description, to our knowledge, of an outbreak of spontaneous staphylococcal arthritis in a rat colony. In a group of 10 rats, 9 displayed arthritis. Clinically, the most obvious findings were arthritis of one or both hindpaws and malaise. Bacteriophage typing showed the common phage type 85 in isolates recovered from the joints, blood, and bedding of rats and from the nose and cheeks of one person from the staff of the animal facility. The S. aureus strain proved to produce staphylococcal enterotoxin A and exhibited strong binding to collagen types I and II and bone sialoprotein, which are potentially important virulence factors. When the recovered S. aureus strain was injected intravenously into healthy rats, severe septic arthritis was induced in almost all of the animals. The arthritic lesions were characterized by infiltration of phagocytic cells and T lymphocytes into the synovium. Many of the synovial cells strongly expressed major histocompatibility complex class II molecules. Increased levels of interleukin 6 in serum as well as a prominent polyclonal B-cell activation were noted throughout the disease course. Pretreatment of S. aureus-injected rats in vivo with an antibody to the alpha beta T-cell receptor significantly decreased the severity of the arthritis. Our results indicate that alpha beta + T lymphocytes contribute to an erosive and persistent course of S. aureus arthritis. Images PMID:8188356

  17. Opiates and cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  18. A rat model for hepatitis E virus

    PubMed Central

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

  19. Distal interstitial epididymitis in young rats.

    PubMed

    Hoffmann, Guenther; Belote, Duane A; Suttie, Andrew W; Buetow, Bernard S; Muhumuza, Luke

    2015-04-01

    A sporadic, diffuse, interstitial mixed cell epididymitis of unknown etiology was noted in the epididymal cauda and distal corpus of young control Sprague-Dawley (SD) rats. Rats from 2 different suppliers were examined as part of routine toxicology studies. The incidence of this finding was 5/5 (study 1), 2/7 (study 2), and 2/7 (study 3). Although 2 of these studies partially overlapped temporally, none of the affected animals from any study was maintained concurrently with affected animals from any of the other 2 studies, and infectious causes, control article toxicity, or autoimmune processes were considered unlikely etiologies. Inflammation similar to that noted in the epididymides of these young rats was not present in other tissues and was not noted in study cohorts sacrificed at ages older than approximately 11 weeks or in rats of similar age from other concurrent studies. Similar findings were noted sporadically in historical control data, and consequently an age-related finding of unknown etiology and occurring in sporadic clusters is reported in SD rats ≤11 weeks old.

  20. Thalidomide decreases intrahepatic resistance in cirrhotic rats.

    PubMed

    Yang, Ying-Ying; Huang, Yi-Tsau; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Kuei-Chuan; Chau, Ga-Yang; Loong, Che-Chuan; Lai, Chiung-Ru; Lee, Shou-Dong

    2009-03-13

    Increased intrahepatic resistance (IHR) within cirrhotic liver is caused by increased endotoxemia, cytokines tumor necrosis factor-alpha (TNF-alpha), vasoconstrictor thromboxane A(2) (TXA(2)), and disrupted microvasculatures. We evaluated the effects of thalidomide-related inhibition of TNF-alpha upon the hepatic microcirculation of cirrhosis in rats. Portal venous pressure (PVP), hepatic TNF-alpha, expression of thromboxane synthase (TXS), and leukocyte common antigen (LCA) were measured in bile-duct-ligated (BDL) rats receiving 1 month of thalidomide (BDL-thalido rats). Portal perfusion pressure (PPP), IHR, and hepatic TXA(2) production were measured in the isolated liver perfusion system. Intravital microscopy was used to examine hepatic microvascular disruptions. In BDL-thalido rats, PVP, PPP, IHR, hepatic TXA(2) and TNF-alpha, hydroxyproline content, expression of TXS and LCA, and LPS-induced leukocyte recruitment were significantly decreased. Conversely, hepatic microvascular density and perfused sinusoids were significantly increased. Thalidomide decreased PVP and IHR by reducing hepatic TXA(2) and improving hepatic microvascular disruptions in rats with biliary cirrhosis.

  1. Diabetic rat testes: morphological and functional alterations.

    PubMed

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  2. Left ventricular volumetric conductance catheter for rats.

    PubMed

    Ito, H; Takaki, M; Yamaguchi, H; Tachibana, H; Suga, H

    1996-04-01

    Left ventricular (LV) volume (V) is an essential parameter for assessment of the cardiac pump function. Measurement of LVV in situ by a conductance catheter method has been widely used in dogs and humans but not yet in small experimental animals such as rats. We instituted a miniaturized six-electrode conductance catheter (3-F) for rat LVV measurement and its signal processing apparatus. We compared stroke volumes (SVs) simultaneously measured with this conductance catheter introduced into the LV through the apex and an electromagnetic flow probe placed on the ascending aorta during gradual decreases in LVV by an inferior vena caval occlusion. A high and linear correlation (r = 0.982) was obtained between these differently measured by SVs pooled from six rats. In another group of three rats, LV pressure was simultaneously measured with a 3-F catheter-tip micromanometer introduced into the LV through the apex. We obtained the slope of the end-systolic pressure-volume (P-V) relationship (Emax) by a gradual ascending aortic occlusion. After administration of propranolol, Emax obviously decreased with no change in volume intercept of the P-V relationship. The conductance volumetry proved to be useful in rats.

  3. The orexigenic effect of orexin-A revisited: dependence of an intact growth hormone axis.

    PubMed

    Álvarez-Crespo, Mayte; Martínez-Sánchez, Noelia; Ruíz-Pino, Francisco; Garcia-Lavandeira, Montserrat; Alvarez, Clara V; Tena-Sempere, Manuel; Nogueiras, Rubén; Diéguez, Carlos; López, Miguel

    2013-10-01

    Fifteen years ago orexins were identified as central regulators of energy homeostasis. Since then, that concept has evolved considerably and orexins are currently considered, besides orexigenic neuropeptides, key modulators of sleep-wake cycle and neuroendocrine function. Little is known, however, about the effect of the neuroendocrine milieu on orexins' effects on energy balance. We therefore investigated whether hypothalamic-pituitary axes have a role in the central orexigenic action of orexin A (OX-A) by centrally injecting hypophysectomized, adrenalectomized, gonadectomized (male and female), hypothyroid, and GH-deficient dwarf rats with OX-A. Our data showed that the orexigenic effect of OX-A is fully maintained in adrenalectomized and gonadectomized (females and males) rats, slightly reduced in hypothyroid rats, and totally abolished in hypophysectomized and dwarf rats when compared with their respective vehicle-treated controls. Of note, loss of the OX-A effect on feeding was associated with a blunted OX-A-induced increase in the expression of either neuropeptide Y or its putative regulator, the transcription factor cAMP response-element binding protein, as well as its phosphorylated form, in the arcuate nucleus of the hypothalamus of hypophysectomized and dwarf rats. Overall, this evidence suggests that the orexigenic action of OX-A depends on an intact GH axis and that this neuroendocrine feedback loop may be of interest in the understanding of orexins action on energy balance and GH deficiency.

  4. Photoperiodic control of reproduction in olfactory-bulbectomized rats.

    PubMed

    Nelson, R J; Zucker, I

    1981-05-01

    30-day-old male rats were (1) sham-operated or subjected to (2) removal of the olfactory bulbs, (3) olfactory bulbectomy and blinding (4) olfactory bulbectomy and pinealectomy or (5) olfactory bulbectomy, blinding and pinealectomy. Animals were exposed from 30 to 110 days of age to long-day (14 h of light per day) or short-day (8 h of light per day) photoperiods. The reproductive system of neurologically-intact rats was not affected by exposure to short days. Nor did bulbectomy affect the reproductive system of rats exposed to long days. However, bulbectomized, short-day rats had significantly lower body weights, reduced testicular and seminal vesicle weights and lower plasma testosterone levels than did bulbectomized, long-day rats. The effects of short-day exposure on bulbectomized rats were prevented by pinealectomy. Short-day exposure and blinding exerted similar effects in bulbectomized rats. The testes of rats from all groups contained elongated spermatids; blinding and short-day treatment had no effect on spermatogenesis. Neither mating behavior nor the number of young sired was influenced by photoperiod in bulbectomized or intact rats. Removal of the olfactory bulbs unmasks photoperiodic responsiveness in rats; the antigonadal effects of short-day exposure are mediated by the pineal gland in bulbectomized rats as in species traditionally designated photoperiodic. The mechanisms by which bulbectomy renders rats responsive to short days are considered.

  5. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  6. EVALUATION OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT BRAIN

    EPA Science Inventory

    This study examined whether there is a differential distribution of PFOS within the brain, and compares adult rats with neonatal rats at an age when formation of the blood-brain barrier is not yet complete (postnatal day 7). Male and female Sprague-Dawley rats (60-70 day old, 4/...

  7. INORGANIC CATIONS IN RAT KIDNEY

    PubMed Central

    Tandler, C. J.; Kierszenbaum, A. L.

    1971-01-01

    For localization of pyroantimonate-precipitable cations, rat kidney was fixed by perfusion with a saturated aqueous solution of potassium pyroantimonate (pH about 9.2, without addition of any conventional fixative). A remarkably good preservation of the tissue and cell morphology was obtained as well as a consistent and reproducible localization of the insoluble antimonate salts of magnesium, calcium, and sodium. All proximal and distal tubules and glomeruli were delimited by massive electron-opaque precipitates localized in the basement membrane and, to a lesser extent, in adjacent connective tissue. In the intraglomerular capillaries the antimonate precipitate was encountered in the basement membranes and also between the foot processes. In addition to a more or less uniform distribution in the cytoplasm and between the microvilli of the brush border, antimonate precipitates were found in all cell nuclei, mainly between the masses of condensed chromatin. The mitochondria usually contained a few large antimonate deposits which probably correspond to the so-called "dense granules" observed after conventional fixations. PMID:4106544

  8. Chronotoxicity of nedaplatin in rats.

    PubMed

    Cui, Yimin; Sugimoto, Koh-Ichi; Kawai, Yoshiko; Sudoh, Toshiaki; Gemba, Munekazu; Fujimura, Akio

    2004-07-01

    Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.

  9. Establishment of rat embryonic stem cells and making of chimera rats.

    PubMed

    Ueda, Shinobu; Kawamata, Masaki; Teratani, Takumi; Shimizu, Taku; Tamai, Yoshitaka; Ogawa, Hiromasa; Hayashi, Katsuyuki; Tsuda, Hiroyuki; Ochiya, Takahiro

    2008-07-30

    The rat is a reference animal model for physiological studies and for the analysis of multigenic human diseases such as hypertension, diabetes, neurological disorders, and cancer. The rats have long been used in extensive chemical carcinogenesis studies. Thus, the rat embryonic stem (rES) cell is an important resource for the study of disease models. Attempts to derive ES cells from various mammals, including the rat, have not succeeded. Here we have established two independent rES cells from Wister rat blastocysts that have undifferentiated characters such as Nanog and Oct3/4 genes expression and they have stage-specific embryonic antigen (SSEA) -1, -3, -4, and TRA-1-81 expression. The cells were successfully cultured in an undifferentiated state and can be possible over 18 passages with maintaining more than 40% of normal karyotype. Their pluripotent potential was confirmed by the differentiation into derivatives of the endoderm, mesoderm, and ectoderm. Most importantly, the rES cells are capable of producing chimera rats. Therefore, we established pluripotent rES cell lines that are widely used to produce genetically modified experimental rats for study of human diseases.

  10. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    PubMed

    Kuramoto, Takashi; Nakanishi, Satoshi; Ochiai, Masako; Nakagama, Hitoshi; Voigt, Birger; Serikawa, Tadao

    2012-01-01

    Albino and hooded (or piebald) rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H) locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h) mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV) element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR) was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i)) phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  11. Neighborhood Sanitation: Rat Complaints and Rat Control on the Near West Side, Newark, New Jersey and North Hill, Akron, Ohio

    ERIC Educational Resources Information Center

    Margulis, Harry L.

    1978-01-01

    Analyses suggest that monthly rate of change in rat complaints is best explained by procedures which increase agency visibility, time-dependent cycles dictated by agency operation and intervention, and dynamics of a rat population. Effective rat control occurs when blocks are environmentally improved and annual cycle links weakened. (Author/MA)

  12. Opportunity Leaves a Trail of 'Rat' Holes

    NASA Technical Reports Server (NTRS)

    2004-01-01

    NASA's Mars Exploration Rover Opportunity's rock abrasion tool, known informally as the 'Rat,' has nibbled seven holes into the slope of 'Endurance Crater.' This image from the rover's navigation camera was released previously (PIA06716) without the Rat holes labeled so that viewers could try to find the holes themselves. Here, the holes have been identified. Starting from the uppermost pictured (closest to the crater rim) to the lowest, the Rat hole targets are: 'Tennessee,' 'Cobblehill,' 'Virginia,' 'London,' 'Grindstone,' 'Kettlestone,' and 'Drammensfjorden.' These holes were drilled on sols 138 (June 13, 2004), 143 (June 18), 145 (June 20), 148 (June 23), 151 (June 26), 153 (June 28) and 161 (July 7), respectively. Each hole is 4.5 centimeters (1.8 inches) in diameter.

  13. Placentophagia in Weanling Female Laboratory Rats

    PubMed Central

    Harding, Kaitlyn M.; Lonstein, Joseph S.

    2014-01-01

    Placentophagia is common in parturient mammals and offers physiological and behavioral advantages for mothers. In natural environments, weanlings are often present during the birth of younger siblings, but it is unknown if weanling rats are placentophagic or prefer placenta over other substances. To examine this, primiparous rats were remated during the postpartum estrus and weanling females remained in the nest during their mother’s next parturition. Continuous observation revealed that 58% of weanlings were placentophagic. To determine if this placentophagia occurs away from parturient mothers, weanling females still living in their natal nest were offered placenta, liver, or cake frosting in a novel chamber. They ingested more placenta and liver than frosting. Thus, many weanling female laboratory rats are placentophagic during birth of younger siblings but do not selectively prefer placenta when tested outside their natal nest. Consequences of placentophagia by weanlings are unknown, but it may promote their alloparenting or postpartum mothering. PMID:24604548

  14. Circadian rhythms of pineal function in rats.

    PubMed

    Binkley, S A

    1983-01-01

    In pineal glands melatonin is synthesized daily. Melatonin synthesis in rats kept in most light-dark cycles occurs during the subjective night. This rhythm, which persists in constant dark, is a circadian rhythm which may be a consequence of another circadian rhythm in the pineal gland, of N-acetyltransferase activity (NAT). The NAT rhythm has been studied extensively in rats as a possible component of the system timing circadian rhythms. The NAT rhythm is driven by neural signals transmitted to the pineal gland by the sympathetic nervous system. Environmental lighting exerts precise control over the timing of the NAT rhythm. In rats, there is enough data to describe a daily time course of events in the pineal gland and to describe a pineal "life history." Hypothetical schemes for generation of the NAT rhythm and for its control by light are presented.

  15. Promotion of rat hepatocarcinogenesis by praziquantel.

    PubMed

    Shirai, T; Joong, K D; Hakoi, K; Thamavit, W; Pairojkul, C; Hoshiya, T; Hasegawa, R; Ito, N

    1991-10-01

    Praziquantel, the widely used anti-helminthic agent, was investigated for hepatocarcinogenesis-promoting potential using a medium-term liver bioassay system for carcinogens. F344 male rats were given a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and then starting 2 weeks later, received praziquantel in the diet at concentrations of 1.5 or 0.5%, or intragastrically at a dose of 1,500 mg/kg once a week for 6 weeks. Control groups received DEN or praziquantel alone. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. Development of glutathione S-transferase placental form-positive foci in the liver was significantly increased in terms of both number and area with the 1.5% dose, while only area was affected by the 0.5% dose. The results thus indicate that praziquantel at high dose has promoting potential in rat hepatocytic tumorigenesis.

  16. Toxicological studies on tienilic acid in rats.

    PubMed

    Oker-Blom, C; Mäkinen, J; Gothoni, G

    1980-07-01

    The subacute oral toxicity of tienilic acid in male and female Sprague--Dawley rats has been studied. Animals were given tienilic acid 0, 30, 120 and 480 mg/kg body weight as a 3% gum arabic suspension for 28 days. At 30 mg tienilic acid blood pressure and serum uric acid decreased. At the two higher dose-levels a slight decrease in hemoglobin and an increase in S-GPT was noticed and there was a significant increase in the liver weight and serum magnesium concentration of male rats, while the liver weight of female rats increased only slightly. On microscopic examination, unicellular necrosis of small groups of liver cells was noted, together with focal round-cell infiltration and some stasis of the two higher dose-levels in some animals. Tienilic acid had no noticeable effects on other organs or parameters.

  17. Body temperature regulation and thermoneutrality in rats.

    PubMed

    Poole, S; Stephenson, J D

    1977-04-01

    Various concepts of thermoneutrality were considered for a proposed study of the role of hypothalamic amines in temperature regulation of rats. The classic definition, the ambient temperature over which metabolic rate is minimum and constant, gave a range of approximately 28 to 32 degrees C. However, within this temperature range rats were inactive, the inactivity apparently representing a behavioural response to heat stress and itself responsible for the reduced metabolic rate; certain thermoregulatory effectors were also activated to increase heat loss. Therefore an alternative range, 18.0 +/- 1.9 (mean +/- S.D.) to 28.1 +/- 1.0 degrees C, was defined in which rats displayed normal activity, behavioural thermoregulations being absent.

  18. Immunologically induced peliosis hepatis in rats.

    PubMed

    Husztik, E; Lázár, G; Szabó, E

    1984-06-01

    Peliosis hepatis has been induced immunologically with anti-rat glomerular basal membrane rabbit serum in rats pre-sensitized with a rare earth metal complex, neodymium pyrocatechin disulphonate (NPD). This is the first experimental evidence that peliosis hepatis may develop as a result of an immunological process. It is noteworthy that in this experimental form of peliosis hepatis and in that observed earlier in rats treated with basic polyglutamic acid derivatives, severe defibrination was detected and, as in most human cases, not only the liver but other organs were also involved in the peliotic lesions. Since the rare earth metal compounds, among them the pyrocatechin disulphonate complex of neodymium, depress the reticulo-endothelial activity, a role of the reticulo-endothelial system in the pathogenesis of this experimental form of peliosis hepatis is suggested.

  19. Weight control and restraint of laboratory rats

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Van Breda Kolff, K.

    1979-01-01

    The use of restrained and confined rats in some procedures used in combustion toxicology introduces the problems of obtaining rats of the appropriate size for the apparatus, and of identifying any artifacts resulting from the use of restraint alone. Feeding studies indicate that controlled feeding of fast-growing strains such as the Sprague-Dawley can hold rat size essentially constant for significant periods of time. The undesirable aspects are the need to cage the animals individually, with resultant psychological as well as metabolic effects. Restraint studies of slow-growing strains such as the Fischer 344 indicate that denying access to food and water for periods of several hours at a time interrupts normal gain only temporarily.

  20. The activity of phosphoenolpyruvate carboxykinase in rat tissues. Assay techniques and effects of dietary and hormonal changes

    PubMed Central

    Pogson, Christopher I.; Smith, Stephen A.

    1975-01-01

    1. Phosphoenolpyruvate carboxykinase was assayed by three methods: (i) incorporation of H14CO3− into oxaloacetate: (ii) conversion of oxaloacetate into phosphoenolpyruvate, subsequently assayed enzymically; and (iii) transfer of 32P from [γ-32P]GTP to oxaloacetate. 2. Enzyme activity is increased in liver and epididymal adipose tissue in alloxan-diabetes and starvation, and in kidney in starved, acidotic and steroid-treated animals. 3. The ratios of the `back' to the `forward' reactions in liver, kidney and epididymal adipose tissue are different and characteristic of each tissue; they differ markedly from values reported for the purified mitochondrial enzyme. 4. The ratio of the `back' to `forward' reaction in any one tissue is constant in adrenalectomized, diabetic, acidotic and steroid-treated animals. 5. In starved animals, the ratio is increased in liver and kidney, but decreased in epididymal adipose tissue. 6. Administration of l-tryptophan results in an acute (1h) increase in activity measured in the `forward' direction alone in liver and epididymal adipose tissue, but not in kidney. PMID:1220693

  1. Acclimation to decompression sickness in rats.

    PubMed

    Montcalm-Smith, E A; McCarron, R M; Porter, W R; Lillo, R S; Thomas, J T; Auker, C R

    2010-03-01

    Protection against decompression sickness (DCS) by acclimation to hyperbaric decompression has been hypothesized but never proven. We exposed rats to acclimation dives followed by a stressful "test" dive to determine whether acclimation occurred. Experiments were divided into two phases. Phase 1 rats were exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid decompression on one of the following regimens: 70 ft of seawater (fsw) for 9 days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days (S40), or unpressurized sham exposure for 9 days (Control). On the day following the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid decompression). Both L70 and S70 rats had significantly lower incidences of DCS than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the other regimens were lower than in Control rats but without statistical significance. Phase 2 used the most protective regimen from phase 1 (L70); rats were exposed to L70 or a similar regimen with a less stressful staged decompression. Another group was exposed to a single acclimation dive (70 fsw/30 min) on the day before the test dive. We observed a nonsignificant trend for the rapidly decompressed L70 dives to be more protective than staged decompression dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not provide protection. We conclude that protection against DCS can be attained with acclimating exposures that do not themselves cause DCS. The deeper acclimation dive regimens (70 fsw) provided the most protection.

  2. Pinealectomy aggravates acute pancreatitis in the rat.

    PubMed

    Jaworek, Jolanta; Zwirska-Korczala, Krystyna; Szklarczyk, Joanna; Nawrot-Porąbka, Katarzyna; Leja-Szpak, Anna; Jaworek, Andrzej K; Tomaszewska, Romana

    2010-01-01

    Melatonin, a pineal indoleamine, protects the pancreas against acute damage; however, the involvement of the pineal gland in the pancreatoprotective action of melatonin is unknown. The primary aim of this study was to determine the effects of pinealectomy on the course of acute caerulein-induced pancreatitis (AP) in rats. AP was induced by a subcutaneous infusion of caerulein (25 μg/kg) into pinealectomized or sham-operated animals. Melatonin (5 or 25 mg/kg) was given via intraperitoneal (ip) injection 30 min prior to the induction of AP. The pancreatic content of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative enzyme, glutathione peroxidase (GSH-Px), were measured in each group of rats. Melatonin blood levels were measured by radioimmunoassay (RIA). In the sham-operated rats, AP was confirmed with histological examination and manifested as pancreatic edema and an increase in the blood lipase level (by 1,500%). In addition, the pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic glutathione peroxydase (GSH-Px) activity was reduced by 40%. Pinealectomy significantly aggravated the histological manifestations of AP, reduced the GSH-Px activity and markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or without AP as compared to sham-operated animals. Melatonin was undetectable in the blood of the pinealectomized rats with or without AP. Treatment with melatonin (25 mg/kg, ip) prevented the development of AP in the sham-operated rats and significantly reduced pancreatic inflammation in the animals previously subjected to pinealectomy. In conclusion, pineal melatonin contributes to the pancreatic protection through the activation of the antioxidative defense mechanism in pancreatic tissue as well as its direct antioxidant effects.

  3. [Berberine inhibits cardiac fibrosis of diabetic rats].

    PubMed

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  4. The oncogenic action of ionizing radiation on rat skin

    SciTech Connect

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs.

  5. Disturbed patterns of behaviour in morphine tolerant and abstinent rats

    PubMed Central

    Kumar, R.; Mitchell, E.; Stolerman, I. P.

    1971-01-01

    1. Eating, drinking and spontaneous motor activity were studied in rats receiving large daily doses of morphine. These forms of behaviour were largely suppressed when the rats were made abstinent and were restored when morphine was given again. 2. Compensation for depressions of behaviour during abstinence did not seem sufficient to account for all the stimulant effects of morphine in tolerant rats. Morphine also had slight stimulant actions in non-tolerant rats. 3. In tolerant rats, the repeated pairing of the effects of morphine with the re-emergence of behaviour such as eating and drinking may intensify the rewarding value of the drug. PMID:5105387

  6. Fenbendazole treatment and litter size in rats.

    PubMed

    Johnston, Nancy A; Bieszczak, Jeremiah R; Verhulst, Steven; Disney, Kimberly E; Montgomery, Kyle E; Toth, Linda A

    2006-11-01

    Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.

  7. Glycoconjugate in rat taste buds.

    PubMed

    Kano, K; Ube, M; Taniguchi, K

    2001-05-01

    The taste buds of the fungiform papillae, circumvallate papilla, foliate papillae, soft palate and epiglottis of the rat oral cavity were examined by lectin histochemistry to elucidate the relationships between expression of glycoconjugates and innervation. Seven out of 21 lectins showed moderate to intense staining in at least more than one taste bud. They were succinylated wheat germ agglutinin (s-WGA). Dolichos biflorus agglutinin (DBA), Bandeiraea simplicifolia lectin-I (BSL-I), Ricinus communis agglutinin-I (RCA-I), peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I) and Phaseolus vulgaris agglutinin-L (PHA-L). UEA-I and BSL-I showed moderate to intense staining in all of the taste buds examined. They strongly stained the taste buds of the epiglottis, which are innervated by the cranial nerve X. UEA-I intensely stained the taste buds of the fungiform papillae and soft palate, both of which are innervated by the cranial nerve VII. The taste buds of circumvallate papilla and foliate papillae were innervated by the cranial nerve IX and strongly stained by BSL-I. Thus, UEA-I and BSL-I binding glycoconjugates, probably alpha-linked fucose and alpha-D-galactose, respectively, might be specific for taste buds. Although the expression of these glycoconjugates would be related to the innervation of the cranial nerve X, the differential expression of alpha-linked fucose and alpha-D-galactose might be related to the innervation of the cranial nerve VII and IX, respectively.

  8. Rat hepatitis E virus: geographical clustering within Germany and serological detection in wild Norway rats (Rattus norvegicus).

    PubMed

    Johne, Reimar; Dremsek, Paul; Kindler, Eveline; Schielke, Anika; Plenge-Bönig, Anita; Gregersen, Henrike; Wessels, Ute; Schmidt, Katja; Rietschel, Wolfram; Groschup, Martin H; Guenther, Sebastian; Heckel, Gerald; Ulrich, Rainer G

    2012-07-01

    Zoonotic hepatitis E virus (HEV) infection in industrialised countries is thought to be caused by transmission from wild boar, domestic pig and deer as reservoir hosts. The detection of HEV-specific antibodies in rats and other rodents has suggested that these animals may represent an additional source for HEV transmission to human. Recently, a novel HEV (ratHEV) was detected in Norway rats from Hamburg, Germany, showing the typical genome organisation but a high nucleotide and amino acid sequence divergence to other mammalian and to avian HEV strains. Here we describe the multiple detection of ratHEV RNA and HEV-specific antibodies in Norway rats from additional cities in north-east and south-west Germany. The complete genome analysis of two novel strains from Berlin and Stuttgart confirmed the association of ratHEV to Norway rats. The present data indicated a continuing existence of this virus in the rat populations from Berlin and Hamburg. The phylogenetic analysis of a short segment of the open reading frame 1 confirmed a geographical clustering of the corresponding sequences. Serological investigations using recombinant ratHEV and genotype 3 capsid protein derivatives demonstrated antigenic differences which might be caused by the high amino acid sequence divergence in the immunodominant region. The high amount of animals showing exclusively ratHEV RNA or anti-ratHEV antibodies suggested a non-persistent infection in the Norway rat. Future studies have to prove the transmission routes of the virus in rat populations and its zoonotic potential. The recombinant ratHEV antigen generated here will allow future seroepidemiological studies to differentiate ratHEV and genotype 3 infections in humans and animals.

  9. Cecal infusion of nutrients improves nutritional status of rats.

    PubMed

    Aghdassi, E; Raina, N; Allard, J P

    1995-11-01

    The role of colonic fermentation in providing energy was investigated in rats with small bowel transection (T) or 80% resection (SBR). Rats were randomized to receive for 12 d either saline (S) or the enteral solution (E) through a cecostomy to meet 30% of energy requirement; the rest (70%) was provided by parenteral nutrition. Although SBR-S rats lost weight significantly compared with d 1 of the study, SBR-E rats gained. Significantly greater carcass wet weight and fat were found in SBR-E and T-E rats compared with SBR-S and T-S rats. SBR-E and T-E rats had significantly greater colonic mucosal dry weight and protein compared with SBR-S and T-S rats. Cecal short-chain fatty acid (SCFA) contents were also significantly higher in SBR-E and T-E rats compared with SBR-S and T-S rats. There was no significant effect of surgery (T vs. SBR) on any of the variables studied. These results suggest that the products of fermentation of an enteral solution infused through a cecostomy contribute substantially to energy requirement, maintenance of body composition and nutritional status of rats.

  10. Renal Function and Hemodynamic Study in Obese Zucker Rats

    PubMed Central

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  11. Effects of electromagnetic radiation on the hemorheology of rats

    NASA Astrophysics Data System (ADS)

    Huang, Zhiwei; Tian, Tian; Xiao, Bo; Li, Wen

    2017-01-01

    The current work examines the effects of electromagnetic radiation on the hemorheology to provide an experimental basis for radiation protection. Electromagnetic radiation was generated by a Helmholtz coil constructed from copper wire. There were six rats altogether: three rats in the experimental group, and three rats in the control group. The rats in the experimental group were continuously exposed to radiation for 10 hours every day, and rats in the control group remained in a normal environment. After 30 days, the characteristics of hemorheology of the two groups were compared. The average plasma viscosity, whole blood high shear velocity, and whole blood low shear viscosity were lower in rats in the experimental group than in rats in the control group, while the whole blood shear viscosity was higher in the experimental group than in the control group. Results suggest that long term exposure to electromagnetic radiation does have certain impacts on the cardiovascular system, deeming it necessary to take preventative measures.

  12. Core temperature of tailless rats exposed to centrifugation

    NASA Technical Reports Server (NTRS)

    Monson, C. B.; Oyama, J.

    1984-01-01

    The role of the tail in the altered thermoregulation of rats during acute exposure to hypergravity was investigated, using groups of rats of two ages: 55 days (young) and 138 days (old). Rectal and foot temperature changes were measured in intact and tailless rats subjected to 1 h centrifugation of 2.8 G, with preceding (1 h) and following (1-3 h) 1 G periods. At 22 C, the loss of body heat from the tail per se does not measurably contribute to the hypothermia induced by hypergravity. However, the heat loss from the feet was greater in the tailless rats than in the intact rats from the young group of animals, although there was no significant difference between the tailless and intact rats in the old animal group. It is concluded that the inhibition of heat production is a significant factor in the hypothermia of centrifuged tailless rats, as it has been previously shown to be in the intact animals.

  13. Aging effects on oxidative phosphorylation in rat adrenocortical mitochondria.

    PubMed

    Solinas, Paola; Fujioka, Hisashi; Radivoyevitch, Tomas; Tandler, Bernard; Hoppel, Charles L

    2014-06-01

    Does aging in itself lead to alteration in adrenocortical mitochondrial oxidative phosphorylation? Mitochondria from Fischer 344 (F344) rats (6 and 24 months old), Brown Norway rats (6 and 32 months old) and F344-Brown Norway hybrid rats (6 and 30 months old) were compared. Mitochondria were isolated from extirpated adrenal cortex. The yields of mitochondria were quantitatively similar in all rat strains irrespective of age. In order to assess the activity of each mitochondrial complex, several different substrates were tested and the rate of oxidative phosphorylation measured. Aging does not affect mitochondrial activity except in the F344 rat adrenal cortex where the maximal ADP-stimulated oxidative phosphorylation decreased with age. We hypothesize that impaired synthesis of steroid hormones by the adrenal cortex with age in F344 rats might be due to decreased adrenocortical mitochondrial oxidative phosphorylation. We conclude that aging results in adrenocortical mitochondria effects that are non-uniform across different rat strains.

  14. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?

    PubMed

    Olivier, B; Chan, J S W; Pattij, T; de Jong, T R; Oosting, R S; Veening, J G; Waldinger, M D

    2006-01-01

    Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.

  15. Derivation of rat embryonic stem cells and generation of protease-activated receptor-2 knockout rats.

    PubMed

    Yamamoto, Satoshi; Nakata, Mitsugu; Sasada, Reiko; Ooshima, Yuki; Yano, Takashi; Shinozawa, Tadahiro; Tsukimi, Yasuhiro; Takeyama, Michiyasu; Matsumoto, Yoshio; Hashimoto, Tadatoshi

    2012-08-01

    One of the remarkable achievements in knockout (KO) rat production reported during the period 2008-2010 is the derivation of authentic embryonic stem (ES) cells from rat blastocysts using a novel culture medium containing glycogen synthase kinase 3 and mitogen-activated protein kinase kinase inhibitors (2i medium). Here, we report gene-targeting technology via homologous recombination in rat ES cells, demonstrating its use through production of a protease-activated receptor-2 gene (Par-2) KO rat. We began by generating germline-competent ES cells from Dark Agouti rats using 2i medium. These ES cells, which differentiate into cardiomyocytes in vitro, can produce chimeras with high ES cell contribution when injected into blastocysts. We then introduced a targeting vector with a neomycin-resistant gene driven by the CAG promoter to disrupt Par-2. After a 7-day drug selection, 489 neomycin-resistant colonies were obtained. Following screening by polymerase chain reaction (PCR) genotyping and quantitative PCR analysis, we confirmed three homologous recombinant clones, resulting in chimeras that transmitted the Par-2 targeted allele to offspring. Par-2 KO rats showed a loss of Par-2 messenger RNA expression in their stomach cells and a lack of PAR-2 mediated smooth muscle relaxation in the aorta as indicated by pharmacological testing. Compared with mice, rats offer many advantages in biomedical research, including a larger body size; consequently, they are widely used in scientific investigation. Thus, the establishment of a gene-targeting technology using rat ES cells will be a valuable tool in human disease model production and drug discovery.

  16. Witnessing traumatic events causes severe behavioral impairments in rats

    PubMed Central

    Patki, Gaurav; Solanki, Naimesh; Salim, Samina

    2015-01-01

    Witnessing a traumatic event but not directly experiencing it can be psychologically quite damaging. In North America alone, ~30% of individuals who witness a traumatic event develop post-traumatic stress disorder (PTSD). While effects of direct trauma are evident, consequences of indirect or secondary trauma are often ignored. Also unclear is the role of social support in the consequences of these experiences. The social defeat paradigm, which involves aggressive encounters by a large Long–Evans male rat (resident) towards a smaller Sprague–Dawley male rat (intruder), is considered a rodent model of PTSD. We have modified this model to create a trauma witness model (TWM) and have used our TWM model to also evaluate social support effects. Basically, when an intruder rat is placed into the home cage of a resident rat, it encounters an agonistic behavior resulting in intruder subordination. The socially defeated intruder is designated the SD rat. A second rat, the cage mate of the SD, is positioned to witness the event and is the trauma witnessing (TW) rat. Experiments were performed in two different experimental conditions. In one, the SD and TW rats were cagemates and acclimatized together. Then, one SD rat was subjected to three sessions of social defeat for 7 d. TW rat witnessed these events. After each social defeat exposure, the TW and SD rats were housed together. In the second, the TW and SD rats were housed separately starting after the first defeat. At the end of each protocol, depression-anxiety-like behavior and memory tests were conducted on the SD and TW rats, blood withdrawn and specific organs collected. Witnessing traumatic events led to depression- and anxiety-like behavior and produced memory deficits in TW rats associated with elevated corticosterone levels. PMID:24887568

  17. Subretinal transplantation of rat MSCs and erythropoietin gene modified rat MSCs for protecting and rescuing degenerative retina in rats.

    PubMed

    Guan, Y; Cui, L; Qu, Z; Lu, L; Wang, F; Wu, Y; Zhang, J; Gao, F; Tian, H; Xu, L; Xu, G; Li, W; Jin, Y; Xu, G-T

    2013-11-01

    For degenerative retinal diseases, like the acquired form exemplified by age-related macular degeneration (AMD), there is currently no cure. This study was to explore a stem cell therapy and a stem cell based gene therapy for sodium iodate (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO-rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The rMSCs were prepared for transplantation after 3 to 5 passages or modified with EPO gene. During the 8 weeks after the transplantation, the rats treated with rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus examination, fundus fluorescein angiography (FFA) and electroretinogram. The transplantation efficiency of donor cells was examined for their survival, integration and differentiation. Following the transplantation, labeled donor cells were observed in subretinal space and adopted RPE morphology. EPO concentration in vitreous and retina of SI-treated rats which were transplanted with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the improvement of retinal morphology and function. These findings suggest that rMSCs transplantation could be a new therapy for degenerative retinal diseases since it can protect and rescue RPE and retinal neurons, while EPO gene modification to rMSCs could be an even better option.

  18. A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in normal and diabetic rats.

    PubMed

    Premalatha, R; Jubendradass, Rajamanickam; Rani, S Judith Amala; Srikumar, K; Mathur, Premendu Prakash

    2013-05-01

    Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3β-HSD and 17β-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.

  19. Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources.

    PubMed

    Zhang-James, Yanli; Middleton, Frank A; Faraone, Stephen V

    2013-07-02

    The spontaneously hypertensive rat (SHR) has been widely used as a model for studies of hypertension and attention deficit/hyperactivity disorder. The inbred Wistar-Kyoto (WKY) rat, derived from the same ancestral outbred Wistar rat as the SHR, are normotensive and have been used as the closest genetic control for the SHR, although the WKY has also been used as a model for depression. Notably, however, substantial behavioral and genetic differences among the WKY substrains, usually from the different vendors and breeders, have been observed. These differences have often been overlooked in prior studies, leading to inconsistent and even contradictory findings. The complicated breeding history of the SHR and WKY rats and the lack of a comprehensive understanding of the genetic background of different commercial substrains make the selection of control rats a daunting task, even for researchers who are mindful of their genetic heterogeneity. In this study, we examined the genetic relationship of 16 commonly used WKY and SHR rat substrains using genome-wide SNP genotyping data. Our results confirmed a large genetic divergence and complex relationships among the SHR and WKY substrains. This understanding, although incomplete without the genome sequence, provides useful guidance in selecting substrains and helps to interpret previous reports when the source of the animals was known. Moreover, we found two closely related, yet distinct WKY substrains that may provide novel opportunities in modeling psychiatric disorders.

  20. Rats do not eat alone in public: Food-deprived rats socialize rather than competing for baits

    PubMed Central

    Ram, Tamar; Zadicario, Pazit; Eilam, David

    2017-01-01

    Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead) to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully. PMID:28278246

  1. Prior access to a sweet is more protective against cocaine self-administration in female rats than in male rats.

    PubMed

    Cason, Angie M; Grigson, Patricia S

    2013-03-15

    It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 [42] for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson and Twining, 2002 [3]). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior.

  2. High-impact exercise strengthens bone in osteopenic ovariectomized rats with the same outcome as Sham rats.

    PubMed

    Honda, Akiko; Sogo, Naota; Nagasawa, Seigo; Shimizu, Takuya; Umemura, Yoshihisa

    2003-09-01

    The effect of jump exercise on middle-aged osteopenic rats was investigated. Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. After the experiment, the right tibia and femur were dissected, and blood was obtained from each rat. OVX rats were observed to have increased body weights and decreased bone mass in their tibiae and femurs. Jump-exercised rats, on the other hand, had significantly increased tibial bone mass, strength, and cortical areas. The bone mass and strength of OVX exercised rats increased to approximately the same extent as Sham exercised rats, despite estrogen deficiency or osteopenia. Our data suggest that jump exercise has beneficial effects on lower limb bone mass, strength, bone mineral density, and morphometry in middle-aged osteopenic rats, as well as in Sham rats.

  3. Rats do not eat alone in public: Food-deprived rats socialize rather than competing for baits.

    PubMed

    Weiss, Omri; Dorfman, Alex; Ram, Tamar; Zadicario, Pazit; Eilam, David

    2017-01-01

    Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead) to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully.

  4. Vldlr overexpression causes hyperactivity in rats

    PubMed Central

    2012-01-01

    Background Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients. Methods We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features. Results Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function. Conclusions Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities. PMID:23110844

  5. Skeletal alterations in rats during space flight

    NASA Astrophysics Data System (ADS)

    Wronski, T. J.; Morey-Holton, E.; Jee, W. S. S.

    Male Wistar rats were placed in orbit for an 18.5 day period aboard the Soviet Cosmos 1129 biological satellite. The skeletal changes which occurred during space flight were a reduced rate of periosteal bone formation in the tibial and humeral diaphyses, a decreased trabecular bone volume, and an increased fat content of the bone marrow in the proximal tibial metaphysis.

  6. The Helsinki Rat Microsurgical Sidewall Aneurysm Model

    PubMed Central

    Marbacher, Serge; Marjamaa, Johan; Abdelhameed, Essam; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana

    2014-01-01

    Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. PMID:25350840

  7. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  8. The effect of ACTH on suckling rats.

    PubMed

    Sato, Y

    1984-01-01

    In the present study, the causes of brain shrinkage induced by synthetic ACTH treatment in epileptic children were investigated using suckling rats. Synthetic ACTH was injected subcutaneously once a day for 5 days into suckling rats aged 15 days. Saline was injected into control subjects in the same way. Rats were sacrificed before the injection, immediately after the repeated injections, and 5 and 14 days from the end of the course of repeated injections. The weight, volume and water content of the brains were measured and the protein, DNA, sodium and potassium contents of the brains were also determined. The mean weight and volume of the brains after 5-day injection of ACTH were slightly smaller compared to those of control rats. No natural increase in brain protein with growth was found from the start of ACTH injections to 14 days after finishing the course of repeated injections. The DNA, sodium and potassium contents of the brains significantly increased immediately after the repeated injections of 5 days. It was suggested that the brain shrinkage of epileptics induced by ACTH treatment might be caused by decreased water content and not cellular degradation.

  9. Voluntary Oral Administration of Losartan in Rats

    PubMed Central

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-01-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  10. Baroreflex Function in Rats after Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Hasser, Eileen M.

    1997-01-01

    Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

  11. Digital replantation teaching model in rats.

    PubMed

    Ad-El, D D; Harper, A; Hoffman, L A

    2000-01-01

    Replant surgery is a complex procedure that requires advanced microsurgical skills and is usually performed as an emergency operation, lasting many hours. For these reasons, teaching replantation is difficult. Although teaching models exist, they are often too general or complicated for routine use and do not simulate the stages and the pitfalls of human replant surgery. We have designed a model that is simple and imitates human replant surgery. After reviewing the rat anatomy, students dissect and replant a rat hind limb that has been sharply amputated by the instructor. They follow the same principles of "real" surgery like debridement, minimizing ischemia time, and stable fixation before anatomosis of vessels. After marking the structures, bony fixation followed by vessel and nerve anastomosis are performed. Muscle is reattached to the skin and limb vascularity evaluated. After we designed this model, plastic surgery residents performed the technique on 10 rats. An 80% limb viability rate was achieved. This model is simple to perform, simulates all the relevant structures and pitfalls of human surgery, and the rats are relatively cheap and can be used for other parallel projects.

  12. Skeletal Alterations in Rats During Space Flight

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey-Holton, E.; Jee, W. S. S.

    1981-01-01

    Male Wistar rats were placed in orbit for an 18.5 day period aboard the Soviet Cosmos 1129 biological satellite. The skeletal changes which occurred during space flight were a reduced rate of periosteal bone formation in the tibial and humeral diaphyses, a decreased trabecular bone volume, and an increased fat content of the bone marrow in the proximal tibial metaphysis.

  13. MODELING OPERANT BEHAVIOR IN THE PARKINSONIAN RAT

    PubMed Central

    Avila, Irene; Reilly, Mark P.; Sanabria, Federico; Posadas-Sánchez, Diana; Chavez, Claudia L.; Banerjee, Nikhil; Killeen, Peter; Castañeda, Edward

    2009-01-01

    Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains 3 parameters representing motor capacity (δ), motivation (a), and short term memory (λ). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson’s disease. Rats were trained to lever press under a 5-component fixed ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of δ increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation. PMID:19073222

  14. METABOLISM AND DOSIMETRY OF VINCLOZOLIN IN RAT

    EPA Science Inventory

    Vinclozolin (V) is an agricultural fungicide. V administered to rats is hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2). V, M1and M2 are antiandrogenic by interacting with the androgen r...

  15. Portal copper transport in rats by albumin

    SciTech Connect

    Gordon, D.T.; Leinart, A.S.; Cousins, R.J.

    1987-03-01

    The distribution of newly absorbed copper among serum proteins obtained from the portal circulation of rats was examined by conventional and high-performance gel filtration chromatography, affinity chromatography, and Western blotting. Within 10-30 min after being administered by gavage or directly into the intestine, /sup 67/Cu and /sup 64/Cu, respectively, were recovered in the albumin fraction. By 8 h after administration of the radionuclides, virtually all of the radioactivity was found with ceruloplasmin. Affigel blue fractionation and subsequent Superose-6 chromatography further demonstrated that all of the copper in the albumin-containing fractions was in fact bound to this protein rather than high molecular weight moieties. Vascular perfusion of the isolated rat intestine, where /sup 64/Cu was infused into the lumen, showed that newly absorbed /sup 64/Cu in the vascular perfusate collected from the cannulated portal vein was associated with albumin. Uptake of radioactivity by isolated rat liver parenchymal cells from medium containing rat serum with /sup 67/Cu bound to albumin was demonstrated. In vitro binding of /sup 64/Cu to serum proteins that were transferred to nitrocellulose by Western blotting techniques showed that albumin is essentially the only protein that binds appreciable amounts of copper. The data suggest that albumin is the plasma protein that is responsible for the initial transport of copper after absorption.

  16. Dermal absorption of inorganic germanium in rats.

    PubMed

    Yokoi, Katsuhiko; Kawaai, Takae; Konomi, Aki; Uchida, Yuka

    2008-11-01

    So-called germanium 'health' products including dietary supplements, cosmetics, accessories, and warm bath service containing germanium compounds and metalloid are popular in Japan. Subchronic and chronic oral exposure of germanium dioxide (GeO(2)), popular chemical form of inorganic germanium causes severe germanium toxicosis including death and kidney dysfunction in humans and experimental animals. Intestinal absorption of neutralized GeO(2) or germanate is almost complete in humans and animals. However, it is not known whether germanium is cutaneously absorbed. We tested dermal absorption of neutralized GeO(2) or germanate using male F344/N rats. Three groups of rats were treated with a 3-h topical application of hydrophilic ointment containing graded level of neutralized GeO(2) (pH 7.4): 0, 0.21 and 0.42 mg GeO(2)/g. Germanium concentration in blood and tissues sampled from rats after topical application of inorganic germanium was measured by inductively coupled plasma-mass spectrometry. Animals topically applied 0.42 mg GeO(2)/g ointment had significantly higher germanium concentrations in plasma, liver, and kidney than those of rats that received no topical germanium. The results indicate that skin is permeable to inorganic germanium ion or germanate and recurrent exposure of germanium compounds may pose a potential health hazard.

  17. Microvascular effects of copper deficiency in rats

    SciTech Connect

    Schuschke, D.A.; Saari, J.T.; Ackermann, D.M.; Miller, F.N. )

    1989-02-15

    We have studied the microcirculatory responses in copper deficient rats using the rat cremaster muscle preparation. Male Sprague-Dawley rats were fed either a copper supplemented diet (CuS, 5 ppm) or a copper deficient diet (CuD, O ppm) for five weeks prior to experimentation. The rats (240-300g) were anesthetized with pentobarbital and the cremaster (with intact nerve and blood supply) were spread in a tissue bath filled with krebs solution. In vivo television microscopy was used to observe the microcirculation. Fluorescein isothiocyanate tagged to bovine serum albumin (FITC-BSA) was injected i.a. 30 min prior to the start of experimentation. In the CuS animals photoactivation of the intravascular FITC-BSA caused significant platelet aggregation and reduction in red blood cell column diameter (RBCCD) by 30 min and stasis of flow by 60 min. In CuD animals there was no reduction in RBCCD and only minor platelet aggregation after 60 min of photoactivation. Topical administration of compound 48/80 (1.0 and 10.0 {mu}g/ml) induced a significantly greater macromolecular leakage (increased interstitial fluorescence of FITC-BSA) in the CuD animals than in the control, CuS animals. These results suggest that copper deficiency results in marked alterations of the regulatory mechanisms governing thrombosis and inflammation.

  18. EXPERIMENTAL ATHEROSCLEROSIS AND CARDIAC INFARCTS IN RATS

    PubMed Central

    Wilgram, George F.

    1959-01-01

    Marked obesity was induced in rats by feeding a high fat, egg yolk-rich diet. The obese rats were hyperlipemic and showed an increased incidence of lipomatous coronary lesions, but did not develop severe atheromatous lesions. Spontaneous vascular lesions of several kinds have been observed in aging rats. Among them, plaques containing a fibrin-like material seem to be conspicuous. However, these lesions differ from the experimentally induced changes, which were more fatty. Atherosclerosis, as it is defined in human pathology, has not been observed to develop spontaneously in rats. Experimental induction of marked hyperlipemia and hypercholesterolemia by feeding a high fat egg yolk-rich diet (supplemented with cholesterol, choleate, and thiouracil), and use of viosterol to cause vascular injury, led to severe atherosclerosis, coronary occlusion, and myocardial infarction. A consideration of all the findings reported here leads to renewed support of the concept that atherosclerosis has a combination of causes (Aschoff, Anitschkow, Page). Of all the etiological factors considered here, elevation of blood lipides and vascular injury are thought to be the most important ones. PMID:13620855

  19. ATRAZINE ALTERS STEROIDOGENESIS IN MALE WISTAR RATS

    EPA Science Inventory

    We have reported that atrazine (ATR, 200 mg/kg x 30 d) causes increased serum estrone (E) and estradiol (E2) in male wistar rats (Toxicol. Sci. 2000, 58:50-59). This study evaluates the short-term effects of ATR on E, E2 and their precursors in the steroidogenic pathway. Sixty-da...

  20. Seasonal variations of cardiac output in rats.

    PubMed

    Back, G; Strubelt, O

    1975-11-15

    Cardiac output of rats shows seasonal variations with low values in spring and summer and high ones in autumn and winter. The stroke volume was much more implicated in these changes than the heart rate. The seasonal changes of cardiac output are probably due to changes of thyroid function.

  1. The Forminalized Rat: A Convenient Microbial Ecosystem.

    ERIC Educational Resources Information Center

    Lee, Adrian

    1984-01-01

    Presents a series of experiments built around the bacteria found in the intestinal tract of formalinized rats as a model for discussing microbial ecology. Describes methods of examination of intestinal content, student tasks, and discussion questions; also gives a challenge problem to solve.

  2. Lobeline produces conditioned taste avoidance in rats.

    PubMed

    Harrod, S B; Dwoskin, L P; Bardo, M T

    2004-05-01

    Previous results indicate that pretreatment with lobeline attenuates methamphetamine (METH) self-administration in rats, but not by acting as a substitute reinforcer. Given these findings, it has been suggested that lobeline may serve as a useful pharmacotherapy for psychostimulant abuse. However, because lobeline produces emesis and nausea in humans, the present study examined whether lobeline has direct effects on taste avoidance behavior in rats within the same dose range shown previously to decrease METH self-administration. Two experiments utilized a Pavlovian conditioning procedure to determine if lobeline produces conditioned taste avoidance (CTA) in rats. In Experiments 1 and 2, rats consumed either novel milk or salt solutions, respectively, and within 10 min, were injected with lobeline (0.3-3.0 mg/kg) or METH (0.3-3.0 mg/kg). A single-bottle test conducted 48 h after flavor-drug pairings indicated that the dose of lobeline that reduced METH self-administration in a previous study (i.e., 3.0 mg/kg) also produced reliable CTA for milk and salt solution. These findings suggest a need to develop lobeline analogs that reduce METH self-administration, but do not produce CTA following the consumption of a novel solution.

  3. Pack rats (Neotoma spp.): Keystone ecological engineers?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The potential role of two species of pack rats (Neotoma albigula and Neotoma micropus) as keystone ecological engineers was examined by estimating the species diversity of invertebrates living in the nest middens, and nitrogen mineralization rates in soils associated with the middens. Although pack-...

  4. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  5. Development of a Rat Model of Hypothermia

    DTIC Science & Technology

    2005-06-01

    Fall and MAJ Len Murray and their animal care technicians, SGT Jeffrey Hunter, SPC Robert Powers and SPC Melissa Valliere vi EXECUTIVE SUMMARY... Bastille . Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats. Can. J. Physiol. Pharmacol. 80:233-243, 2002

  6. Naltrexone-induced hypothermia in the rat.

    PubMed

    Ary, M; Chesarek, W; Sorensen, S M; Lomax, P

    1976-10-01

    Naltrexone, in relatively high doses, has been reported to cause a fall in body temperature in human ex-heroin addicts who had been abstinent for at least 6 weeks. The underlying mechanism of this hypothermic effect has been investigated in rats. The first consideration was that the temperature change was a reflection of delayed withdrawal but rats implanted with a morphine pellet 45 days earlier showed no significant change in temperature after a dose of naltrexone that caused marked withdrawal hypothermia in dependent rats implanted 3 days previously. A fall in core temperature was only induced in rats after doses of 80 and 160 mg/kg i.p. of naltrexone. Behavioral thermoregulatory studies revealed that the animals correct the falling body temperature by increased exposure to a radiant heat source indicating that the central thermostats had not been significantly affected by the drug. These data suggest that the major component in the hypothermic effect of naltrexone is activation of efferent heat loss pathways or peripheral heat loss mechanisms. Due to current suggestions that opiate receptors might represent the receptors for an endogenous transmitter the results are discussed in relation to this consideration. When compared to the sites and mechanism of action of opiates on thermoregulation the results with naltrexone lend little support to the hypothesis that the fall in temperature is due to displacement of an endogenous substance from central opiate receptors.

  7. Excretion of bisphenol A into rat milk.

    PubMed

    Okabayashi, Ken; Watanabe, Toshi

    2010-03-01

    Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the production of polycarbonate plastic and epoxy resins. This study analyzed the BPA concentration in rat milk, in order to assess the risk of BPA transfer to the offspring via milk. The rats ingested BPA by oral administration or by drinking the water in a polycarbonate bottle, and the milk samples were collected using an automated experimental milker. The BPA concentration in the samples of milk, drinking water, and food was analyzed by LC/MS. In the case of milk samples obtained from rats injected with BPA at 2, 4, 8, and 24 h prior to milking, the BPA concentrations were 0.462 +/- 0.182 ppm, 0.138 +/- 0.0185 ppm, 0.080 +/- 0.0197 ppm, and 0.0232 +/- 0.0051 ppm, respectively. Also, in the cases of the water sample left in polycarbonate bottle and the milk sample obtained from rats provided it as drinking water, the concentrations of BPA were 0.000332 +/- 0.00015 ppm and 0.0184 +/- 0.0050 ppm, respectively. The results indicate that the BPA administered to the dams was transferred to their milk, and that BPA concentration in milk was higher at the early period after the single bolus dose. Additionally, these results reveal that sequential elution of BPA from polycarbonate containers in a much diluted form would undergo bioaccumulation in dams and likely be transferred to pups via milk in a much concentrated form.

  8. Voluntary Oral Administration of Losartan in Rats.

    PubMed

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  9. NAT THE RAT - PUPIL'S BOOK. (TITLE SUPPLIED).

    ERIC Educational Resources Information Center

    ROJAS, PAULINE M.; AND OTHERS

    THE EXPERIMENTAL EDITION OF "NAT THE RAT" REPRESENTS LEVEL TWO OF THE "MIAMI LINGISTIC READERS" DESIGNED TO BE USED IN TEACHING BEGINNING READING TO PUPILS WHOSE PRESCHOOL LANGUAGE WAS OTHER THAN ENGLISH. THE FIVE MAJOR CHARACTERS IN THE STORY ARE INTRODUCED ON THE FIRST FIVE PAGES OF THE PUPILS' BOOK. ILLUSTRATIONS (BLACK AND…

  10. THE FINE STRUCTURE OF THE RAT CEREBELLUM

    PubMed Central

    Herndon, Robert M.

    1964-01-01

    This paper describes the fine structure of the granule cells, stellate neurons, astrocytes, Bergmann glia, oligodendrocytes, and microglia of the rat cerebellum after fixation by perfusion with buffered 1 per cent osmium tetroxide. Criteria are given for differentiating the various cell types, and the findings are correlated with previous light microscope and electron microscope studies of the cerebellum. PMID:14222815

  11. Rat pro-opiomelanocortin contains sulfate

    SciTech Connect

    Hoshina, H.; Hortin, G.; Boime, I.

    1982-07-02

    Intermediate lobes isolated from rat pituitary glands incorporated (/sup 35/S)sulfate into pro-opiomelanocortin and other adrenocorticotropic hormone-containing peptides. Incubation of intermediate lobes in medium containing the arginine analog canavanine inhibited the cleavage of pro-opiomelanocortin into smaller products. Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated.

  12. Endocrine and metabolic aspects of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    SciTech Connect

    Gorski, J.R.

    1988-01-01

    Toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were characterized in male Sprague-Dawley rats in order to elucidate the mechanism of acute toxicity of this potent halogenated hydrocarbon. Studies in TCDD-treated, pair-fed control and ad libitum-fed control rates, as well as in thyroidectomized, adrenalectomized and hypophysectomized, revealed differential hormonal, toxicologic and histophathologic responses suggesting that these manifestations of TCDD exposure are the results of an insult to intermediary metabolism. Tissue specific alterations in de novo fatty acid synthesis were directly related to differential changes observed in thyroid hormone homeostasis. The increased hepatic de novo fatty acid synthesis provided a likely mechanism for the documented fact that TCDD-treated rats lose more body weight than corresponding pair-fed controls because de novo fatty acid synthesis represents an energy inefficient metabolic process. Experiments in adrenalectomized and hypophysectomized rats led to the hypothesis that severe hypoglycemia due to inhibition of gluconeogenesis is the cause of TCDD-induced death. A subsequent characterization of gluconeogenesis in TCDD-treated rats confirmed this hypothesis.

  13. Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands

    PubMed Central

    Franssen, Frits; Swart, Arno; van Knapen, Frans; van der Giessen, Joke

    2016-01-01

    Background Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We aimed to study the intestinal and intramuscular helminths in wild rats from three different environments to assess the relevance of rats as carrier of zoonotic parasites for public health. Materials and methods Wild brown rats (117 individuals) and black rats (44 individuals) were captured at farms, in suburban and in rural environments in the Netherlands. Intestinal helminths were isolated and identified morphologically. Artificial digestion was used to isolate muscle larvae. Results and discussion Morphological analysis of rat intestinal contents yielded six nematode species (Syphacia muris, Heterakis spumosa, Aonchotheca murissylvatici, Trichuris muris, Nippostrongylus brasiliensis, and Strongyloides sp.), three cestode species (Hymenolepis diminuta, H. nana and Hymenolepis (=Rodentolepis) fraterna), and four trematode species (Plagiorchis muris, Plagiorchis proximus, Echinostoma chloropodis, and Notocotylus imbricatus). Black rats at farms displayed the lowest intestinal helminth species variation (six species) and carried overall on average 0.93 species simultaneously. In comparison, brown rats at farms carried seven helminth species and 1.91 species simultaneously. Brown rats from suburban environments displayed the highest species variation (11 species) at 1.82 simultaneous helminth species. Absence of trematodes from rats at farms may suggest limited exchange of rats between farms and surrounding wet rural environments. We report four species of veterinary (Syphacia muris) or zoonotic relevance (Hymenolepis diminuta, Hymenolepis nana and Plagiorchis muris). We did not find Trichinella muscle larvae, consistent with long-term prevalence in Dutch wild rats. PMID

  14. Coordination strategies for limb forces during weight-bearing locomotion in normal rats, and in rats spinalized as neonates

    PubMed Central

    Giszter, Simon F; Davies, Michelle R; Graziani, Virginia

    2010-01-01

    Some rats spinally transected as neonates (ST rats) achieve weight-supporting independent locomotion. The mechanisms of coordinated hindlimb weight support in such rats are not well understood. To examine these in such ST rats and normal rats, rats with better than 60% of weight supported steps on a treadmill as adults were trained to cross an instrumented runway. Ground reaction forces, coordination of hindlimb and forelimb forces and the motions of the center of pressure were assessed. Normal rats crossed the runway with a diagonal trot. On average hindlimbs bore about 80% of the vertical load carried by forelimbs, although this varied. Forelimbs and hindlimb acted synergistically to generate decelerative and propulsive rostrocaudal forces, which averaged 15% of body weight with maximums of 50% . Lateral forces were very small (<8% of body weight). Center of pressure progressed in jumps along a straight line with mean lateral deviations <1 cm. ST rats hindlimbs bore about 60% of the vertical load of forelimbs, significantly less compared to intact (p<0.05). ST rats showed similar mean rostrocaudal forces, but with significantly larger maximum fluctuations of up to 80% of body weight (p<0.05). Joint force-plate recordings showed forelimbs and hindlimb rostrocaudal forces in ST rats were opposing and significantly different from intact rats (p<0.05). Lateral forces were ~20% of body weight and significantly larger than in normal rats (p<0.05). Center of pressure zig-zagged, with mean lateral deviations of ~ 2cm and a significantly larger range (p<0.05). The haunches were also observed to roll more than normal rats. The locomotor strategy of injured rats using limbs in opposition was presumably less efficient but their complex gait was statically stable. Because forelimbs and hindlimbs acted in opposition, the trunk was held compressed. Force coordination was likely managed largely by the voluntary control in forelimbs and trunk. PMID:18612631

  15. Acetaminophen Induces Apoptosis in Rat Cortical Neurons

    PubMed Central

    Posadas, Inmaculada; Santos, Pablo; Blanco, Almudena; Muñoz-Fernández, Maríangeles; Ceña, Valentín

    2010-01-01

    Background Acetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. Methodology/Principal Findings We report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM) that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/Kg) that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial–mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/Kg) injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. Conclusions/Significance The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment) are present. PMID:21170329

  16. Ontogeny of the rat hepatic adrenoceptors

    SciTech Connect

    McMillian, M.K.

    1985-01-01

    Hepatic alpha-1, alpha-2, and beta-2 adrenoceptors were characterized during development of the rat through Scatchard analysis of (/sup 3/H)-prazosin, (/sup 3/H)-rauwolscine and (/sup 125/I)-pindolol binding to washed particle membrane preparations. Major changes in adrenoceptor number occur shortly before birth and at weaning. The fetal rat liver is characterized by a large number of alpha-2 adrenoceptors which falls 10-20 fold at birth. The number of hepatic beta adrenoceptors decreases 30-50% during the third week after birth increases slightly at weaning, then decreases gradually in the adult. Hepatic alpha-1 adrenoceptor number increases 3-5 fold at weaning to become the predominant adrenoceptor in the adult rat liver. The basis for the fall in alpha-2 number at birth remains unclear. The fall in beta receptor number at the end of the second week post-natally appears dependent on increased insulin and corticosterone secretion as well as increased NE release form nerve terminals. The basis for the increase in beta number at weaning and the sex-dependent loss of beta function but not receptor number in the adult rat remains unknown. The dramatic increases in alpha-1 number and function at weaning are dependent on increased adrenocortical secretion, adrenalectomy prevents the normal. This effect of adrenocorticoids might be mediated through glycogen, as glycogen depletion during fasting decreases alpha-1 receptor number and function at weaning are dependent on increased adrenocortical secretion, adrenalectomy prevents the normal. This effect of adrenocorticoids might be mediated through glycogen, as glycogen depletion during fasting decreases alpha-1 receptor number and function. These findings suggest that hepatic adrenoceptor number adapts from the low carbohydrate diet of the suckling rat to the high carbohydrate diet of the adult at weaning.

  17. Thallium kinetics in rat cardiac transplant rejection

    SciTech Connect

    Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

    1988-04-01

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

  18. Laser welding of rat's facial nerve.

    PubMed

    Hwang, Kun; Kim, Sun Goo; Kim, Dae Joong; Lee, Chang Hyun

    2005-11-01

    The aim of this study is to compare regeneration of the severed nerves that were repaired by laser welding with those repaired by microsurgical suturing and evaluate the value in use of laser nerve welding in the head and neck area. In 12 rats the buccal branches of the facial nerves on the both sides were transected, and CO2 laser welding of the epineurium was performed on the right side and microsurgical suture technique was applied on the left side. In six rats Cholera Toxin B Subunit (CTb) was injected in the epineurium distal to the nerve anastomosis site at postoperative week 4. Another six rats were treated exactly in the same way in postoperative week 8. Six normal rats were used as controls. Intact facial nerve was observed after injection of CTb as well. Neurons of facial nuclei labeled positively by CTb were detected immunohistochemically, and the numbers were counted. CTb-positive neurons in the control group were 1311 +/- 258 (n = 6). CTb-positive neurons in the group (n = 6) with laser nerve welding were 1174 +/- 122 in postoperative week 4 and 1562 +/- 565 in postoperative week 8. CTb-positive neurons in the group (n = 6) with microsurgical suture were 1066 +/- 89 in postoperative week 4 and 1443 +/- 531 in postoperative week 8. CTb-positive neurons were seen significantly more in the group with laser welding than in the group with microsurgical suture in postoperative week (P = 0.028), but there was not much difference in postoperative week 8 (P = 0.463). None of 12 rats showed dehiscence at the nerve anastomosis done by laser welding. This study shows that nerve regeneration is more apparent in the nerve repaired by laser welding than in that repaired by microsurgical suture.

  19. Cerebral microbleeds in a neonatal rat model

    PubMed Central

    Carusillo Theriault, Brianna; Woo, Seung Kyoon; Karimy, Jason K.; Keledjian, Kaspar; Stokum, Jesse A.; Sarkar, Amrita; Coksaygan, Turhan; Ivanova, Svetlana; Gerzanich, Volodymyr

    2017-01-01

    Background In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. Methods Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. Results mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. Conclusions In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. PMID:28158198

  20. Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.

    PubMed

    Németi, Balázs; Gregus, Zoltán

    2013-03-18

    Dimethylarsinic acid (DMAs(V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs(III)), is highly toxic. Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs(V) reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain. Therefore, the reduction of DMAs(V) to DMAs(III) in rats and in rat liver cytosol was studied to better understand its mechanism. To assess DMAs(V) reduction in rats, a novel procedure was devised based on following the accumulation of red blood cell (RBC)-bound dimethylarsenic (DMAs), which represents DMAs(III), in the blood of DMAs(V)-injected anesthetized rats. These studies indicated that rats reduced DMAs(V) to DMAs(III) to a significant extent, as in 90 min 31% of the injected 50 μmol/kg DMAs(V) dose was converted to DMAs(III) that was sequestered by the circulating erythrocytes. Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs(V) and the accumulation of RBC-bound DMAs, whereas the indirect methyltransferase inhibitor periodate-oxidized adenosine was without effect. Assessment of DMAs(V)-reducing activity of rat liver cytosol revealed that reduction of DMAs(V) required cytosolic protein and GSH and was inhibited by thiol reagents, GSSG and dehydroascorbate. Although thioredoxin reductase (TRR) inhibitors (aurothioglucose and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction. On ultrafiltration of the cytosol through a 3 kDa filter, the reducing activity in the retentate was lost but was largely restored by NADPH. Such experiments also suggested that the reducing enzyme was larger than 100 kDa and was not GSTO1. In summary, reduction of DMAs(V) to the highly toxic DMAs(III) in rats and rat liver cytosol is a GSH

  1. The effects of adrenalectomy and corticsteroid injection on the fibrinolytic activity of complex heparin compounds in the blood during immobilization

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Lomovskaya, E. G.; Shapiro, F. B.; Lyapina, L. Y.

    1980-01-01

    Total non-enzymatic fibrinolytic activity in the blood of rats increased three times in response to stress caused by 30 minute immobilization, and the activity of epinephrine-heparin complex increased nine times. In adrenalectomized animals, which showed a weak response to the same stress, intraperitoneal injection of hydrocortisone 30 minutes prior to immobilization normalized the response. Obtained results indicate that adrenalectomy leads to sharp reduction of heparin complexing with thromogenic proteins and epinephrine, while substitution therapy with hydrocortisone restores anticoagulation system function.

  2. Hyperammonemia and orotic aciduria in portacaval-shunted rats.

    PubMed

    Steele, R D

    1984-01-01

    The effect of a portacaval shunt-induced alteration in liver function on nitrogen metabolism was studied in rats. Within a few days after surgery, portacaval-shunted rats grew with an average daily gain in body weight equal to sham-operated control rats. Within 1 week after surgery, portacaval-shunted rats excreted 20% more orotic acid in their urine compared to control rats. The difference increased to 37% after 3 weeks. Plasma ammonia levels were elevated by 78% in portacaval-shunted rats compared to control rats after 2 weeks. Portacaval-shunted rats injected with a challenging load of ammonium chloride (5 mmol/kg) excreted half as much orotic acid in their urine over a 24-hour period as similarly injected controls. The simultaneous injection of 1.5 mmol/kg of arginine prevented the ammonia-induced increase in orotic acid excretion in both shunted and control rats. However, feeding rats diets supplemented with 1% arginine did not prevent the chronic hyperammonemia and orotic aciduria produced by the construction of portacaval shunts. Similar experiments with diets supplemented with 1% sodium benzoate to induce alternative pathways for nitrogen excretion were also without effect. These results are in contrast to recent clinical studies reporting the effectiveness of sodium benzoate in treating hyperammonemia in patients with urea cycle enzyme defects.

  3. Intracerebroventricular injection of ghrelin decreases wheel running activity in rats.

    PubMed

    Miyatake, Yumiko; Shiuchi, Tetsuya; Mawatari, Kazuaki; Toda, Satomi; Taniguchi, Yasuko; Futami, Akari; Sato, Fukiko; Kuroda, Masashi; Sebe, Mayu; Tsutsumi, Rie; Harada, Nagakatsu; Minokoshi, Yasuhiko; Kitamura, Tadahiro; Gotoh, Koro; Ueno, Masaki; Nakaya, Yutaka; Sakaue, Hiroshi

    2017-01-01

    There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model. SPORTS rats showed lower levels of serum ghrelin compared with those of the parental line of Wistar rats. Intracerebroventricular and intraperitoneal injection of ghrelin decreased wheel-running activity in SPORTS rats. In addition, daily injection of the ghrelin inhibitor JMV3002 into the lateral ventricles of Wistar rats increased wheel-running activity. Co-administration of obestatin inhibited ghrelin-induced increases in food intake but did not inhibit ghrelin-induced suppression of voluntary exercise in rats. Growth hormone secretagogue receptor (GHSR) in the hypothalamus and hippocampus of SPORTS rats was not difference that in control rats. We created an arcuate nucleus destruction model by administering monosodium glutamate (MSG) to neonatal SPORTS rats. Injection of ghrelin into MSG-treated rats decreased voluntary exercise but did not increase food intake, suggesting that wheel-running activity is not controlled by the arcuate nucleus neurons that regulate feeding. These results provide new insights into the mechanism by which ghrelin regulates voluntary activity independent of arcuate nucleus neurons.

  4. Sodium status influences chronic amphotericin B nephrotoxicity in rats.

    PubMed Central

    Ohnishi, A; Ohnishi, T; Stevenhead, W; Robinson, R D; Glick, A; O'Day, D M; Sabra, R; Jackson, E K; Branch, R A

    1989-01-01

    The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats. PMID:2802551

  5. Study of the effects of ozone in emphysematous rats

    SciTech Connect

    Dormans, J.A.; van Bree, L.; Boere, A.J.; Marra, M.; Rombout, P.J.

    1989-01-01

    The effects of short-term exposure to ozone on control and elastase-induced emphysematous rats were examined to investigate whether emphysema would change the pulmonary susceptibility to oxidant air pollution. Emphysema was induced in rats after a single intratracheal instillation of 0.2 IU elastase/g body weight. Histologically, panacinar emphysema was apparent at 2, 4, 8, and 16 wk, that is, the total duration of the experiment. The diagnosis was confirmed by morphometry: the mean linear intercepts (MLI) of elastase-treated rats were significantly increased at all observation times, whereas the internal surface areas (ISA) of the elastase-treated rats were significantly decreased. In addition, pulmonary function tests provided supportive evidence for the diagnosis of emphysema. Respiratory system compliance and functional residual capacity showed a significant increase in elastase-treated rats. No differences in inspiratory capacity or in forced vital capacity between control rats and elastase-treated rats were observed. The above data are indicative for a rat model for elastase-induced emphysema. Short-term exposure to ozone of elastase-treated rats revealed panacinar emphysema, including an inflammatory response in the centroacinar region. No differences in MLI as well as in ISA between ozone-exposed rats (with or without emphysema) and their respective controls were observed. Short-term exposure to ozone induced an identical, significant increase in protein content, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities in lungs of normal and emphysematous rats. Moreover, these results strongly suggest that emphysematous rats are not more susceptible to ozone than nonemphysematous rats.

  6. Metabolic responses to head-down suspension in hypophysectomized rats

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Tipton, C. M.; Evans, J.; Linderman, J. K.; Gosselink, K.; Grindeland, R. E.

    1993-01-01

    Rats exposed to head-down suspension (HDS) exhibit reductions in maximal O2 consumption (VO2max) and atrophy of select hindlimb muscles. This study tested the hypothesis that an endocrine-deficient rat exposed to HDS would not exhibit reductions in VO2max or hindlimb muscle mass. Hypophysectomized (HYPX) and sham-operated (SHAM) rats were tested for VO2max before and after 28 days of HDS or cage control (CC) conditions. No significant reductions in VO2max were observed in HYPX rats. In contrast, SHAM-HDS rats exhibited a significant reduction in absolute (-16%) and relative (-29%) measures of aerobic capacity. Time course experiments revealed a reduction in VO2max in SHAM-HDS rats within 7 days, suggesting that cardiovascular adjustments to HDS occurred in the 1st wk. HDS was associated with atrophy of the soleus (-42%) in SHAM rats, whereas HYPX rats exhibited atrophy of the soleus (-36%) and plantaris (-13%). SHAM-HDS rats had significantly lower (-38%) soleus citrate synthase activities per gram muscle mass than SHAM-CC, but no significant differences existed between HYPX-HDS and -CC rats. HDS rats had an impaired ability to thermoregulate, as indicated by significantly greater temperature increases per unit run time, compared with their CC counterparts. Pretreatment plasma epinephrine levels were significantly lower in HYPX than in SHAM rats. Norepinephrine concentration was similar for all groups except HYPX-HDS, in which it was significantly higher. HDS had no significant effect on thyroxine or triiodothyronine. SHAM-HDS rats had significantly lower concentrations of testosterone and growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS).

  7. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  8. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure.

    PubMed

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-02-26

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah(-/-) Il2rg(-/-) rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat.

  9. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    PubMed Central

    Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  10. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    PubMed

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

  11. [Neurotoxicity of 1-bromopropane in rats].

    PubMed

    Ohnishi, A; Ishidao, T; Kasai, T; Arashidani, K; Hori, H

    1999-03-01

    Neurotoxicity of 1-bromopropane (1-BP) used as an alternative solvent of fluorocarbons was experimentally studied. Eight rats in the experimental group were exposed to 1-BP at 1500 ppm for six hours a day, five days a week for four weeks in an exposure chamber. Another eight rats in the control group were exposed to room air in a similar exposure chamber as those in the experimental group. During the latter half of the fourth week of exposure, all the rats in the experimental group showed a loss of body weight and ataxic gait compared with control rats. At the end of the fourth week, the rats in both groups were perfused through the ascending aorta and fixed. The cerebellum, medulla oblongata, spinal cord and peripheral nerve were processed for histopathological studies. No statistically significant difference in the frequency of axonal degeneration in both peroneal and sural nerves was found between the experimental and control groups. In the cerebellum, the frequency of degeneration of Purkinje cells in both the vermis and hemisphere was higher in the experimental group than in the control group (P < 0.05). There was no significant difference in the frequency of myelin ovoids in the fifth thoracic and in the third cervical posterior columns of the spinal cord between control and experimental groups. There was also no significant difference in the frequency of axonal swelling in the nucleus gracilis of the medulla oblongata between control and experimental groups. Ataxic gait was considered to be induced by degeneration of Purkinje cells in the cerebellum due to 1-BP exposure. However, degenerative findings of nerve fibers in the peripheral nerve, spinal posterior column and nucleus gracilis of the medulla oblongata due to 1-BP exposure were not evident. At the end of the fourth week of exposure, rats in the experimental group showed loss of body weight and markedly decreased motor activities, and it was considered that they would die if we continued the exposure

  12. Relationship of roof rat population indices with damage to sugarcane

    USGS Publications Warehouse

    Lefebvre, Lynn W.; Engeman, Richard M.; Decker, David G.; Holler, Nicholas R.

    1989-01-01

    Roof rats (Rattus rattus) cause substantial damage to sugarcane in South Florida (Samol 1972; Lefebvre et al. 1978, 1985). Accurate estimates of roof rat populations in sugarcane fields would be useful for determining when to to treat a field to control roof rats and for assessing the efficacy of control. However, previous studies have indicated that roof rats exhibit trap shyness, which makes capture-recapture population estimates difficult (Lefebvre et al. 1978, 1985; Holler et al., 1981). Until trapping methods are sufficiently improved to allow accurate population estimates, indices of population size that relate to damage need to be developed. The objectives of our study were to examine the relationship of several indices of roof rat populations to the percentage of sugarcane stalks damaged at harvest; to determine which population index would be most useful for sugarcane growers; and to report on a test of several types of live traps for roof rats.

  13. The emerging role for rat models in gene discovery

    PubMed Central

    Dwinell, Melinda R.; Lazar, Jozef; Geurts, Aron M.

    2011-01-01

    Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review, we will briefly outline the rat models, bioinformatic tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and ultimately, to improve human health will be discussed. Finally, our perspectives on how rat models will continue to positively impact biomedical research will be provided. PMID:21732192

  14. Diseases Transmitted by Man's Worst Friend: the Rat.

    PubMed

    Fox, James G

    2015-12-01

    Historically, the rat has been considered a scourge to mankind, for example, rats infected with the plague bacillus that caused the Black Death, which accounted for millions of deaths in Europe during the Middle Ages. At least three pandemics (in the 5th and 6th, 8th through 14th, and 19th through 21st centuries) of plague ravaged civilizations, and the disease undoubtedly plagued humankind prior to recorded history. Also, numerous other diseases are spread to humans by rats; thus, a quote from Hans Zinsser's text Rats, Lice, and History, "Man and rat will always be pitted against each other as implacable enemies," conveys the general revulsion that society holds for the wild rat.

  15. Taurine in the osmoregulation of the Brattleboro rat

    SciTech Connect

    Nieminen, M.J.; Tuomisto, L.; Solatunturi, E.; Eriksson, L.; Paasonen, M.K.

    1988-01-01

    The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and /sup 3/H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

  16. Prazosin lowers plasma triglyceride concentration in rats: a preliminary report.

    PubMed

    Reaven, G M; Dall'Aglio, E

    1982-01-01

    Prazosin was administered by intraperitoneal injection (0.3 or 3.0 mg/kg) to normal chow-fed male rats for 14 days. Mean +/- SEM plasma triglyceride levels were lower (p less than 0.001) in the prazosin-treated rats (74 +/- 12 mg/dl and 72 +/- 9 mg/dl) than in saline-injected control rats (115 +/- 11 mg/dl). This effect was associated with commensurate reductions in very low density lipoprotein-triglyceride secretion in prazosin-treated rats. No changes were noted in either plasma total or high density lipoprotein cholesterol concentrations. In addition, prazosin was capable of reducing by approximately 50% the elevation in plasma triglyceride concentration produced by a high glucose diet in control rats. The mechanism of the observed effect of prazosin on very low density lipoprotein metabolism in the rat remains to be defined.

  17. The effect of diet fat on rat adipocyte glucose transport.

    PubMed

    Ip, C; Tepperman, H M; De Witt, J; Tepperman, J

    1977-05-01

    Rats were fed either a high fat diet (67% of calories as lard) or high glucose diet (67% of calories as glucose) for 7-8 days. Basal and insulin stimulated net uptake of D glucose (D-L) and 2 deoxy D glucose uptake by free fat cells of fat rats were depressed. Net transport of D glucose (D-L) by purified adipocyte plasma membranes of fat red rats was also diminished. Incubation of fat cells from glucose fed rats with insulin before homogenization for membrane preparation increased net D glucose transport by subsequently purified membranes in two experiments to a greater extent than in similar preparations from rat fed rats. These experiments suggest that fat feeding modifies the plasma membranes of fat cells so that both glucose transport and the stimulatory effect of insulin on the process are decreased.

  18. Sleep deprivation in the rat: III. Total sleep deprivation.

    PubMed

    Everson, C A; Bergmann, B M; Rechtschaffen, A

    1989-02-01

    Ten rats were subjected to total sleep deprivation (TSD) by the disk apparatus. All TSD rats died or were sacrificed when death seemed imminent within 11-32 days. No anatomical cause of death was identified. All TSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (TSC) rats remained healthy. Since dehydration was ruled out and several measures indicated accelerated use rather than failure to absorb nutrients, the food-weight changes in TSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all TSD rats increased EE, with mean levels reaching more than twice baseline values.

  19. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    SciTech Connect

    Lure, M.D.; Fields, M.; Lewis, C.G. Univ. of Maryland, College Park Georgetown Univ., Washington, DC )

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  20. Spatial memory in the desert kangaroo rat (Dipodomys deserti).

    PubMed

    Langley, C M

    1994-03-01

    Desert kangaroo rats (Dipodomys deserti) forage for seed distributed in patches in the desert environment and may remember patch locations. In Experiment 1, 7 desert kangaroo rats that had discovered the location of a plastic token in 1 box accurately dug for a token hidden in the same location in a 2nd identical box. Results of Experiment 2 indicated that the rats primarily remembered the spatial location of the token within the box in relation to extramaze objects and the walls of the experimental box. Female rats also remembered the chip's location in relation to objects inside the box, but males did not. Experiment 3 demonstrated that the rats' ability to locate the buried token did not depend on detection of the odor of the token. In the discussion I propose that spatial memory in kangaroo rats may have evolved as a result of an overall change in the ontogeny of the species rather than as a specialized adaptation for foraging efficiency.

  1. Cysteamine depletes prolactin in young and old hyperprolactinemic rats

    SciTech Connect

    Simpkins, J.W.; Estes, K.S.; Millard, W.J.; Sagar, S.M.; Martin, J.B.

    1983-05-01

    Studies were undertaken to evaluate the effects of cysteamine on serum and anterior pituitary concentrations of prolactin in hyperprolactinemic female rats. Serum prolactin was elevated in young (4 to 5 months old) rats by implantation of 17 beta-estradiol while 26- to 28-month-old rats were in constant estrus and exhibited an age-related hyperprolactinemia. At 4 h after treatment with cysteamine (90 mg/kg body wt) serum and anterior pituitary prolactin concentrations were reduced in young animals by 98 and 85%, respectively. In old constant-estrous rats, cysteamine reduced serum prolactin by 92% and anterior pituitary prolactin by 82%. In young pseudopregnant rats, cysteamine induced a prompt resumption of estrous cycles. These studies indicate that cysteamine is an effective depletor of serum and pituitary prolactin in hyperprolactinemic rats.

  2. Germline transmission of a novel rat embryonic stem cell line derived from transgenic rats.

    PubMed

    Men, Hongsheng; Bauer, Beth A; Bryda, Elizabeth C

    2012-09-20

    Germline-competent rat embryonic stem (ES) cell lines are important resources for the creation of mutant rat models using ES-cell-based gene targeting technology. The ability to isolate germline-competent ES cell lines from any rat strain, including genetically modified strains, would allow for more sophisticated genetic manipulations without extensive breeding. Sprague Dawley (SD) males carrying an enhanced green fluorescent protein (EGFP) transgene were used as the founder animals for the derivation of ES cell lines. A number of ES cell lines were established and subjected to rigorous quality control testing that included assessment of pluripotency factor expression, karyotype analysis, and pathogen/sterility testing. Two male ES cell lines, SD-Tg.EC1/Rrrc and SD-Tg.EC8/Rrrc, were injected into blastocysts recovered from a cross of Dark Agouti (DA) males with SD females. Resulting chimeric animals were bred with wild-type SD mates to verify the germline transmissibility of the ES cell lines by identifying pups carrying the ES cell line-derived EGFP transgene. While both ES cell lines gave rise to chimeric animals, only SD-Tg.EC1 was germline competent. This confirms the feasibility of deriving germline-competent ES cell lines from transgenic rat strains and provides a novel ES cell line with a stable green fluorescent protein (GFP) reporter for future genetic manipulations to create new rat models.

  3. Rat umbilical cord blood cells attenuate hypoxic–ischemic brain injury in neonatal rats

    PubMed Central

    Nakanishi, Keiko; Sato, Yoshiaki; Mizutani, Yuka; Ito, Miharu; Hirakawa, Akihiro; Higashi, Yujiro

    2017-01-01

    Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells. PMID:28281676

  4. The Metabolism and Toxicity of Menthofuran in Rat Liver Slices and in Rats

    PubMed Central

    Khojasteh, S. Cyrus; Oishi, Shimako; Nelson, Sidney D.

    2010-01-01

    Menthofuran is a monoterpene present in mint plants that is oxidized by mammalian cytochrome P450 (CYP)1 to hepatotoxic metabolites. Evidence has been presented that p-cresol and other unusual oxidative products are metabolites of menthofuran in rats, and that p-cresol may be responsible in part for the hepatotoxicity caused by menthofuran (Madyastha and Raj, Drug Metabolism and Disposition 20, 295–301, 1992). In the present study, several oxidative metabolites of menthofuran were characterized in rat and human liver microsomes, and in rat liver slices exposed to cytotoxic concentrations of menthofuran. Metabolites that were identified were monohydroxylation products of the furanyl and cyclohexyl groups, mintlactones and hydroxymintlactones, a reactive γ-ketoenal, and a glutathione conjugate. A similar spectrum of metabolites was found in urine 24 hr after the administration of hepatotoxic doses of menthofuran to rats. In no case was p-cresol (or any of the other reported unusual oxidative metabolites of menthofuran) detected above background concentrations that were well below concentrations of p-cresol that cause cytotoxicity in rat liver slices. Thus, the major metabolites responsible for the hepatotoxic effects of menthofuran appear to be a γ-ketoenal and/or epoxides formed by oxidation of the furan ring. PMID:20945912

  5. City rats: insight from rat spatial behavior into human cognition in urban environments.

    PubMed

    Yaski, Osnat; Portugali, Juval; Eilam, David

    2011-09-01

    The structure and shape of the urban environment influence our ability to find our way about in the city. Understanding how the physical properties of the environment affect spatial behavior and cognition is therefore a necessity. However, there are inherent difficulties in empirically studying complex and large-scale urban environments. These include the need to isolate the impact of specific urban features and to acquire data on the physical activity of individuals. In the present study, we attempted to overcome the above obstacles and examine the relation between urban environments and spatial cognition by testing the spatial behavior of rats. This idea originated from the resemblance in the operative brain functions and in the mechanisms and strategies employed by humans and other animals when acquiring spatial information and establishing an internal representation, as revealed in past studies. Accordingly, we tested rats in arenas that simulated a grid urban layout (e.g. Manhattan streets) and an irregular urban layout (e.g. Jerusalem streets). We found that in the grid layout, rat movement was more structured and extended over a greater area compared with their restricted movement in the irregular layout. These movement patterns recall those of humans in respective urban environments, illustrating that the structure and shape of the environment affect spatial behavior similarly in humans and rats. Overall, testing rats in environments that simulate facets of urban environments can provide new insights into human spatial cognition in urban environments.

  6. Generation of TALEN-mediated FH knockout rat model.

    PubMed

    Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Zhirui; Fan, Huijie; Yuan, Long; Xu, Benling; Yuan, Yuan; Zhang, Hongquan; Ji, Zhenyu; Wen, Jian-Guo; Zhang, Mingzhi; Nesland, Jahn M; Suo, Zhenhe

    2016-09-20

    Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/-) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/- KO rats. There was no behaviour difference between the FH+/- KO and the control rats except that the FH+/- KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/- KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/- kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/- KO rat model, which will be useful for further functional FH studies.

  7. The oncogenic action of ionizing radiation on rat skin

    SciTech Connect

    Burns, F.J.; Garte, S.J.

    1990-01-01

    An extensive experiment involving approximately 400 rats exposed to the neon ion beam at the Bevalac in Berkeley, CA and to electrons is nearing completion. Progress is described in three areas corresponding to the specific aims of the proposal: (1) carcinogenesis and DNA strand breaks in rat skin following exposure by the neon ions or electrons; (2) oncogene activation in radiation-induced rat skin cancers; (3) DNA strand breaks in the epidermis as a function of radiation penetration. 59 refs., 4 tabs.

  8. Distraction of skeletal muscle: evolution of a rat model.

    PubMed

    Green, Stuart A; Horton, Eric; Baker, Michael; Utkan, Ali; Caiozzo, Vincent

    2002-10-01

    To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.

  9. Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats

    PubMed Central

    Esquifino, Ana I; Cano, Pilar; Zapata, Agustín; Cardinali, Daniel P

    2006-01-01

    Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of

  10. A Virtual Rat for Simulating Environmental and Exertional Heat Stress

    DTIC Science & Technology

    2014-10-02

    A virtual rat for simulating environmental and exertional heat stress Vineet Rakesh,1 X Jonathan D. Stallings,2 and Jaques Reifman1 1Department of...Health Research, Fort Detrick, Maryland Submitted 8 July 2014; accepted in final form 18 September 2014 Rakesh V, Stallings JD, Reifman J. A virtual rat ...different heat-stress conditions. To this end, we used our previously published virtual rat , which is capable of computing the spatiotemporal

  11. Generation of TALEN-mediated FH knockout rat model

    PubMed Central

    Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Zhirui; Fan, Huijie; Yuan, Long; Xu, Benling; Yuan, Yuan; Zhang, Hongquan; Ji, Zhenyu; Wen, Jian-Guo; Zhang, Mingzhi; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/−) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/− KO rats. There was no behaviour difference between the FH+/− KO and the control rats except that the FH+/− KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/− KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/− kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/− KO rat model, which will be useful for further functional FH studies. PMID:27556703

  12. Leptin Influences Healing in the Sprague Dawley Rat Fracture Model

    PubMed Central

    Liu, Pengcheng; Cai, Ming

    2017-01-01

    Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing. PMID:28088810

  13. Rapid avoidance acquisition in Wistar-Kyoto rats.

    PubMed

    Servatius, R J; Jiao, X; Beck, K D; Pang, K C H; Minor, T R

    2008-10-10

    The relationship between trait stress-sensitivity, avoidance acquisition and perseveration of avoidance was examined using male Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. Behavior in an open field was measured prior to escape/avoidance (E/A) acquisition and extinction. E/A was assessed in a discrete trial lever-press protocol. The signal-shock interval was 60s with subsequent shocks delivered every 3s until a lever-press occurred. A 3-min flashing light safety signal was delivered contingent upon a lever-press (or failure to respond in 5 min). WKY rats displayed phenotypic low open field activity, but were clearly superior to SD rats in E/A performance. As avoidance responses were acquired and reached asymptotic performance, SD rats exhibited "warm up", that is, SD rats rarely made avoidance responses on the initial trial of a session, even though later trials were consistently accompanied with avoidance responses. In contrast, WKY rats did not show the "warm up" pattern and avoided on nearly all trials of a session including the initial trial. In addition to the superior acquisition of E/A, WKY rats demonstrated several other avoidance features that were different from SD rats. Although the rates of nonreinforced intertrial responses (ITRs) were relatively low and selective to the early safety period, WKY displayed more ITRs than SD rats. With removal of the shocks extinction was delayed in WKY rats, likely reflecting their nearly perfect avoidance performance. Even after extensive extinction, first trial avoidance and ITRs were evident in WKY rats. Thus, WKY rats have a unique combination of trait behavioral inhibition (low open field activity and stress sensitivity) and superior avoidance acquisition and response perseveration making this strain a good model to understand anxiety disorders.

  14. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity.

    PubMed

    Shivers, Kai-Yvonne; Amador, Nicole; Abrams, Lisa; Hunter, Deirtra; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2015-04-01

    Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic-pituitary-adrenal (HPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17β-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX+OVX operation at baseline and post formalin injection. Formalin significantly increased pro-inflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naïve conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased pro-inflammatory tumor necrosis factor (TNF)-α and IL-1β levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol's modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord.

  15. Amino acid metabolism and protein synthesis in lactating rats fed on a liquid diet.

    PubMed Central

    Barber, T; García de la Asunción, J; Puertes, I R; Viña, J R

    1990-01-01

    1. Amino acid metabolism was studied in control virgin rats, lactating rats and virgin rats protein-pair-fed with the lactating rats (high-protein virgin rats). 2. Urinary excretion of nitrogen and urea was higher in lactating than in control virgin rats, and in high-protein virgin rats it was higher than in lactating rats. 3. The activities of urea-cycle enzymes (units/g) were higher in high-protein virgin than in lactating rats, except for arginase. In lactating rats the activities of carbamoyl-phosphate synthase, ornithine carbamoyltransferase and argininosuccinate synthase were lower than in control virgin rats. When the liver size is considered, the activities in lactating rats were similar to those in high-protein virgin rats, except for arginase. 4. N-Acetylglutamate content was higher in high-protein virgin rats than in the other two groups. 5. The rate of urea synthesis from precursors by isolated hepatocytes was higher in high-protein virgin rats than in the other two groups. 6. The flooding-dose method (L-[4-3H]phenylalanine) for measuring protein synthesis was used. The absolute synthesis rates of mammary gland, liver and small-intestinal mucosa were higher in lactating rats than in the other two groups, and in high-protein virgin rats than in control virgin rats 7. These results show that the increased needs for amino acids during lactation are met by hyperphagia and by a nitrogen-sparing mechanism. PMID:2396994

  16. Dental abnormalities in the osteopetrotic rat mutation microphthalmia blanc.

    PubMed

    Cielinski, M J; Iizuka, T; Marks, S C

    1994-11-01

    Dental manifestations of the mild, transient osteopetrosis in the rat mutation microphthalmia blanc (mib) were examined. Eruption of all teeth was delayed in mib rats compared to normal littermates. The delays ranged from 5 days for incisors to 3 and 2 days for the first and second molars. Normal rats had straight incisors in the sagittal plane that exhibited signs of wear, but in mib littermates the incisors were maloccluded, distorted, and showed no signs of wear. Radiographic and histological examination of the dentition of 1- and 4-week-old rats revealed that the apical end of incisors in mib rats failed to extend posteriorly to the third molar region as in normal siblings, but ended at the first molar. Histological examination of longitudinal sections of mandibles through the incisors of neonatal normal and mib rats showed that in 1-day-old mutants the incisor was closely surrounded by alveolar bone to which it was ankylosed. The incisor body in mib rats was also malformed, with an indented apical end. This ankylosis was temporary, being resolved by 3 days. These findings show that neonatal reductions in bone resorption cause incisor defects and delay the eruption of all teeth in mib rats. The malocclusion and distortion of incisors of mib rats are likely caused by temporary ankylosis of incisor matrices to alveolar bone. Taken together, these findings illustrate the concept that bone resorption is an essential and rate-limiting element of tooth eruption.

  17. ENU mutagenesis to generate genetically modified rat models.

    PubMed

    van Boxtel, Ruben; Gould, Michael N; Cuppen, Edwin; Smits, Bart M G

    2010-01-01

    The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach for generating genetically modified rats has been the target-selected N-ethyl-N-nitrosourea (ENU) mutagenesis-based technology. Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism.

  18. The effect of magnesium depletion on thyroid function in rats

    SciTech Connect

    Hsu, J.M.; Root, A.W.; Duckett, G.E.; Smith, J.C. Jr.; Yunice, A.A.; Kepford, G.

    1984-08-01

    The effects of dietary magnesium (Mg) depletion on thyroid function were studied in young male rats. The rats were fed a semipurified diet containing either 12 ppm Mg (deficient rats) or 662 ppm Mg (control rats) for 14 to 28 days. Results showed that the Mg-deficient rats had decreased body weight gain, lowered concentrations of plasma thyroxine (T4) and Mg, but increased weight of the thyroid gland when expressed in proportion to the body weight (milligrams/100 g). There was no difference in the accumulation (uptake) of 131I, 24 hours after Na131I injection, between the Mg-deficient and Mg-supplemented rats. The protein-bound 131I (PB131I) level and the ratio of PB131I to total 131I in plasma was significantly reduced in Mg-deficient rats. Serum thyroid-stimulating hormone (TSH) levels after thyrotropin-releasing hormone injection (TRH, 50 ng/100 g body weight) increased fivefold at 30 minutes, but declined to near the basal level at 2 hours in both groups. No consistent difference in TSH response was observed between the two treatments. Serum T4 response to TRH challenge was significantly reduced in Mg-deficient as compared to Mg-adequate rats at all time intervals. The reduction of T4 level could be due to an impaired T4 synthesis or release in Mg-deficient rats.

  19. Fasting prevents acute pancreatitis induced by cerulein in rats.

    PubMed

    Otsuki, M; Tani, S; Okabayashi, Y; Fujii, M; Nakamura, T; Fujisawa, T; Koide, M; Itoh, H

    1990-07-01

    We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.

  20. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    PubMed Central

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco; Haaning, Line Lindegaard; Jensen, Torben Heick

    2014-01-01

    In S. cerevisiae, the 5′-3′ exonuclease Rat1p partakes in transcription termination. Although Rat1p-mediated RNA degradation has been suggested to play a role for this activity, the exact mechanisms by which Rat1p helps release RNA polymerase II (RNAPII) from the DNA template are poorly understood. Here we describe a function of Rat1p in regulating phosphorylation levels of the C-terminal domain (CTD) of the largest RNAPII subunit, Rpb1p, during transcription elongation. The rat1-1 mutant exhibits highly elevated levels of CTD phosphorylation as well as RNAPII distribution and transcription termination defects. These phenotypes are all rescued by overexpression of the CTD phosphatase Fcp1p, suggesting a functional relationship between the absence of Rat1p activity, elevated CTD phosphorylation, and transcription defects. We also demonstrate that rat1-1 cells display increased RNAPII transcription kinetics, a feature that may contribute to the cellular phenotypes of the mutant. Consistently, the rat1-1 allele is synthetic lethal with the rpb1-E1103G mutation, causing increased RNAPII speed, and is suppressed by the rpb2-10 mutation, causing slowed transcription. Thus, Rat1p plays more complex roles in controlling transcription than previously thought. PMID:24501251

  1. MODELING VOLATILE ORGANIC COMPOUND PHARMACOKINETICS IN RAT PUPS

    EPA Science Inventory

    PBPK model predictions of internal dosimetry in young rats were compared to adult animals for benzene, chloroform (CHL), methylene chloride, methyl ethly ketone (MEK), perchloroethylene, and trichloroethylene.

  2. Toxicological analysis in rats subjected to heroin and morphine overdose.

    PubMed

    Strandberg, Joakim J; Kugelberg, Fredrik C; Alkass, Kanar; Gustavsson, Anna; Zahlsen, Kolbjørn; Spigset, Olav; Druid, Henrik

    2006-09-30

    In heroin overdose deaths the blood morphine concentration varies substantially. To explore possible pharmacokinetic explanations for variable sensitivity to opiate toxicity we studied mortality and drug concentrations in male Sprague-Dawley rats. Groups of rats were injected intravenously (i.v.) with heroin, 21.5 mg/kg, or morphine, 223 mg/kg, causing a 60-80% mortality among drug-naïve rats. Additional groups of rats were pre-treated with morphine for 14 days, with or without 1 week of subsequent abstinence. Brain, lung and blood samples were analyzed for 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. i.v. morphine administration to drug-naïve rats resulted in both rapid and delayed deaths. The brain morphine concentration conformed to an exponential elimination curve in all samples, ruling out accumulation of morphine as an explanation for delayed deaths. This study found no support for formation of toxic concentration of morphine-6-glucuronide. Spontaneous death among both heroin and morphine rats occurred at fairly uniform brain morphine concentrations. Morphine pre-treatment significantly reduced mortality upon i.v. morphine injection, but the protective effect was less evident upon i.v. heroin challenge. The morphine pre-treatment still afforded some protection after 1 week of abstinence among rats receiving i.v. morphine, whereas rats given i.v. heroin showed similar death rate as drug-naïve rats.

  3. Zinc feeding and fertility of male rats.

    PubMed

    Samanta, K; Pal, B

    1986-01-01

    Supplementation of the diet of adult male rats with 4,000 ppm zinc as ZnSO4 for 30 to 32 days increased the zinc content in the testis and sperm by 25 and 18 per cent respectively, but did not change the same in accessory reproductive tissues, e.g. epididymis, seminal vesicle and prostate. The incidence of conception from mating between normal females and zinc fed males was lower as compared to mating between normal females and control males. This observation indicated reduced fertility of the males resulting from additional zinc ingestion. Motility of the sperm collected from the epididymis (tail) of the zinc treated rats was found to be inhibited. It has been suggested that excess zinc in the sperm was responsible for their poor motility and hence a reduced fertilising capacity.

  4. Optical coherence tomography of the rat cochlea

    NASA Astrophysics Data System (ADS)

    Wong, Brian J.; de Boer, Johannes F.; Park, Boris H.; Chen, Zhongping; Nelson, J. Stuart

    2000-10-01

    Optical coherence tomography (OCT) was used to image the internal structure of a rat cochlea (ex vivo). Immediately following sacrifice, the temporal bone of a Sprague-Dawley rat was harvested. Axial OCT cross sectional images (over regions of interest, 1 X 1 mm-2 X 8 mm) were obtained with a spatial resolution of 10 - 15 micrometers . The osseous borders of the lateral membranous labyrinth overlying the cochlea and the scala vestibuli, media, and tympani, which were well demarcated by the modiolus, Reissner's and the basilar membranes, were clearly identified. OCT can be used to image internal structures in the cochlea without violating the osseous labyrinth using simple surgical exposure of the promontory, and may potentially be used to diagnose inner ear pathology in vivo in both animal and human subjects labyrinth.

  5. Propranolol modifies platelet serotonergic mechanisms in rats.

    PubMed

    Zółtowski, R; Pawlak, R; Matys, T; Pietraszek, M; Buczko, W

    2002-06-01

    Though the mechanisms for the vascular actions of vasodilatory beta-blockers are mostly determined, some of their interactions with monoaminergic systems are not elucidated. Because there are evidences supporting a possible involvement of serotonin (5-HT) in the actions of beta-blockers, we studied the effect of propranolol on peripheral serotonergic mechanisms in normotensive and Goldblatt two-kidney - one clip (2K1C) hypertensive rats. In both groups of animals propranolol decreased systolic blood pressure, significantly increased whole blood serotonin concentration and at the same time it decreased platelet serotonin level. The uptake of the amine by platelets from hypertensive animals was lower than that of normotensive animals and it was decreased by propranolol only in the latter. In both groups propranolol inhibited potentiation of ADP-induced platelet aggregation by serotonin. In conclusion, this study provides evidence that propranolol modifies platelet serotonergic mechanisms in normotensive and renal hypertensive rats.

  6. Decalcification of calcium polycarbophil in rats.

    PubMed

    Yamada, T; Saito, T; Takahara, E; Nagata, O; Tamai, I; Tsuji, A

    1997-03-01

    The in vivo decalcification of calcium polycarbophil was examined. The decalcification ratio of [45Ca]calcium polycarbophil in the stomach after oral dosing to rats was more than 70% at each designated time and quite closely followed in the in vitro decalcification curve, indicating that the greater part of the calcium ion is released from calcium polycarbophil under normal gastric acidic conditions. The residual radioactivity in rat gastrointestine was nearly equal to that after oral administration of either [45Ca]calcium chloride + polycarbophil. The serum level of radioactivity was nearly equal to that after oral dosing of [45Ca]calcium lactate. These results indicate that the greater part of orally administered calcium polycarbophil released calcium ions to produce polycarbophil in vivo.

  7. Serotonergic innervation of the rat testis.

    PubMed

    Campos, M B; Vitale, M L; Calandra, R S; Chiocchio, S R

    1990-03-01

    The presence of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. in perchloric extracts of each isolated compartment of the adult rat testis. The testicular capsule, interstitial cells and interstitial fluid contained 5-HT, but 5-HT was not detected in the tubular compartment. In a group of adult rats, one testis was unilaterally denervated, and the contralateral testis used as control. The superior spermatic nerve, arising from the renal plexus, was excised and 1 week after surgery 5-HT content was measured in the capsule and interstitial fluid of both testes. Denervation caused a significant fall (34%) in 5-HT content. These results indicate that at least part of the testicular 5-HT derives from a serotonergic innervation of the gonad.

  8. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  9. Apples prevent mammary tumors in rats.

    PubMed

    Liu, Rui Hai; Liu, Jiaren; Chen, Bingqing

    2005-03-23

    Regular consumption of fruits and vegetables has been consistently shown to be associated with reduced risk of developing chronic diseases such as cancer and cardiovascular disease. Apples are commonly consumed and are the major contributors of phytochemicals in human diets. It was previously reported that apple extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. Phytochemicals, including phenolics and flavonoids, are suggested to be the bioactive compounds contributing to the health benefits of apples. Here it is shown that whole apple extracts prevent mammary cancer in a rat model in a dose-dependent manner at doses comparable to human consumption of one, three, and six apples a day. This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective strategy for cancer protection.

  10. Vapor inhalation of alcohol in rats.

    PubMed

    Gilpin, Nicholas W; Richardson, Heather N; Cole, Maury; Koob, George F

    2008-07-01

    Alcohol dependence constitutes a neuroadaptive state critical for understanding alcoholism, and various methods have been utilized to induce alcohol dependence in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation provides certain advantages over other chronic alcohol exposure procedures that share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol vapor inhalation allows the experimenter to control the dose, duration, and pattern of alcohol exposure. Also, this procedure facilitates testing of somatic and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor produces increases in alcohol-drinking behavior, increases in anxiety-like behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory protocol is flexible, and the parameters of this procedure can be adjusted to accommodate the specific aims of different experiments. This unit describes the options available to investigators using this procedure for dependence induction, when different options are more or less appropriate, and the implications of each.

  11. Methylmercury toxicity in spontaneously hypertensive rats (SHR)

    SciTech Connect

    Tamashiro, H.; Arakaki, M.; Akagi, H.; Hirayama, K.; Smolensky, M.H.

    1986-05-01

    Information is scant on both environmental and individual factors as potentiators of methylmercury (MeHg) toxicity in human beings and other animal species. Hypertension is quite common among the inhabitants of MeHg-polluted areas. It is of special interest to learn what is the health consequence among the hypertensives who have been exposed to MeHg for a prolonged period of time. This study was designed to delineate the toxicity of MeHg in animals having high blood pressure using the laboratory model of spontaneously hypertensive rats (SHR). This paper presents the mortality as well as distribution of mercury in the tissues of SHR and control rats treated orally with methylmercury chloride for 10 consecutive days.

  12. Influence of spaceflight on rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Martin, Thomas P.; Edgerton, V. Reggie; Grindeland, Richard E.

    1988-01-01

    The effect of a 7-day spaceflight (aboard NASA's SL-3) on the size and the metabolism of single fibers from several rat muscles was investigated along with the specificity of these responses as related to the muscle type and the size of fibers. It was found that the loss of mass after flight was varied from 36 percent in the soleus to 15 percent in the extensor digitorum longus. Results of histochemical analyses showed that the succinate dehydrogenase (SDH) activity in muscles of flight-exposed rats was maintained at the control levels, whereas the alpha-glycerol phosphate dehydrogenase (GPD) activity was either maintained or increased. The analyses of the metabolic profiles of ATPase, SDH, and GPD indicated that, in some muscles, there was an increase in the poportion of fast oxidative-glycolytic fibers.

  13. Amantadine stimulates sexual behavior in male rats.

    PubMed

    Ferraz, M R; Santos, R

    1995-08-01

    The effects of amantadine on sexual behavior, penile erection, and seminal emission of male rats was studied. Amantadine significantly decreased latency of mounts in all doses (1.25 to 50 mg/kg), and decreased the number of mounts and intromission latency at the highest doses used. The lowest dose of amantadine significantly increased ejaculation latency and intromission frequency, while higher doses significantly reduced it, which indicates a biphasic response of the drug. Additionally, seminal emission, erections, and genital grooming were significantly induced by amantadine. Amantadine-induced seminal emissions were impaired by spinal cord transection, which suggests the involvement of supraspinal structures in the drug action. Haloperidol and atropine sulphate significantly reduced seminal emissions and penile erections induced by amantadine. These results demonstrate that amantadine stimulates sexual behavior and genital reflexes in male rats and suggest a facilitatory effect of the drug that probably involves different mechanisms of action.

  14. D-RATS 2011: RAFT Protocol Overview

    NASA Technical Reports Server (NTRS)

    Utz, Hans

    2011-01-01

    A brief overview presentation on the protocol used during the D-RATS2011 field test for file transfer from the field-test robots at Black Point Lava Flow AZ to Johnson Space Center, Houston TX over a simulated time-delay. The file transfer actually uses a commercial implementation of an open communications standard. The focus of the work lies on how to make the state of the distributed system observable.

  15. Attention and stimulus processing in the rat.

    PubMed

    Muir, J L

    1996-06-01

    There is little doubt that rats are an essential species in laboratory testing. Given the substantial amount of anatomical and pharmacological information which is available for this species, rats are the animal of choice for many initial neurobiological investigations of the basic mechanisms of learning and memory as well as for pharmacological screening. Indeed, the study of brain-behaviour interactions is greatly facilitated in the rat given the ease with which brain transmitter systems and structures can be selectively manipulated, in contrast to the technical difficulties involved in undertaking such techniques in non-human primates. However, when considering the processing of information that occurs during cognitive processes such as learning and memory it is important to remember that fundamental to such processes are mechanisms of attention. When considering the concept of attentional functioning, it is important to keep in mind that attention is not a unitary construct but consists of several distinct mechanisms: vigilance, divided attention and selective attention, not all of which have been adequately modelled in the rat. Furthermore, attentional processes are also involved in learning operant discrimination tasks and appear to be quite different from those involved in maintaining high levels of trained performance. Consideration of discrimination learning is important given that firstly, during such learning the animal must select from the environment those stimuli which are relevant and secondly, that this type of learning is obviously inherent in many other tests used to assess cognitive function, such as delayed matching-to-sample procedures. Such issues will therefore form the basis of the following discussion.

  16. Improved purification of rat intestinal lactase.

    PubMed

    Nsi-Emvo, E; Launay, J F; Raul, F

    1986-02-01

    A rapid and improved method to obtain purified lactase from rat intestine is described. The purification procedure involved only two chromatographic steps. The degree of purification was far above (500 fold) the values reached with classical methods. Rabbit antisera raised to the purified lactase were characterized using conventional immunological techniques. The specificity of the lactase antibodies was confirmed by the lack of interference on maltase, aminopeptidase and alkaline phosphatase activities measured after papain extraction of the membrane proteins.

  17. Toxicity evaluation of crankcase oil in rats

    PubMed Central

    Arise, R.O.; Tella, A.C.; Akintola, A.A.; Akiode, S.O.; Malomo, S.O.

    2012-01-01

    The aim of this study was to investigate the effect of crankcase oil on the cellular and functional integrity of rat skin. Thirty (30) rats were randomly grouped into six viz groups A-F. Group A (base-line control) received 2 ml of distilled water. 2.5 %, 5.0 %, 7.5 %, and 10.0 % v/v of the crankcase oil were prepared using unused oil as solvent and 2 ml of the concentrations were topically administered to groups C-F respectively for seven consecutive days. Group B served as positive control and received 2 ml of the unused oil. The rats were sacrificed 24 hours after the last administration, and blood and part of the skin were collected. Alkaline phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD) and malondialdehyde level in the blood and skin samples collected were evaluated. Elemental analysis of the crankcase oil was also carried out. The result revealed high lead, iron and chromium levels. Blood lead concentration of rats was significantly (P<0.05) high after seven days of administration. ALP level in skin and serum increased significantly (P<0.05) with the concentration of crankcase oil. There was a significant decrease (P<0.05) in skin ACP activity while it increased significantly (P<0.05) in the serum. Similar results were observed in the SOD levels of the serum and the skin. The level increased significantly (P<0.05) in groups D-F when compared with controls. The MDA concentration of both serum and skin were significantly (P<0.05) elevated. This suggests toxic potential of used lubricating oil and its potential predisposition to cancer. PMID:27366138

  18. Chemical Renal Denervation in the Rat

    SciTech Connect

    Consigny, Paul M. Davalian, Dariush; Donn, Rosy Hu, Jie; Rieser, Matthew Stolarik, DeAnne

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  19. Oxalic acid decreases calcium absorption in rats

    SciTech Connect

    Weaver, C.M.; Martin, B.R.; Ebner, J.S.; Krueger, C.A.

    1987-11-01

    Calcium absorption from salts and foods intrinsically labeled with /sup 45/Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO/sub 3/ and CaCl/sub 2/ than from CaC/sub 2/O/sub 4/ (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

  20. Fate of circulating renin in conscious rats

    SciTech Connect

    Kim, S.; Iwao, H.; Nakamura, N.; Ikemoto, F.; Yamamoto, K.

    1987-01-01

    Highly purified /sup 125/I-labeled rat renal renin (/sup 125/I-renin) was given intravenously to conscious rats to study the fate of circulating renin. Specific antirat renin antiserum was used to identify the labeled renin molecules. In sham-operated rats, the disappearance of /sup 125/I-renin from the plasma showed two exponential components with a half-life of 6.7 +/- 0.4 min for the rapid component and 65.1 +/- 5.7 min for the slow component. The metabolic clearance rate was 11.4 +/- 1.0 ml X min-1 X kg-1. In bilaterally nephrectomized rats, the metabolic clearance rate of /sup 125/I-renin was reduced by 55%, but the half-life of the slow component remained unchanged. Seventy percent hepatectomy caused a 54% decrement in the metabolic clearance and prolonged the half-life of the slow component. Five minutes after injection of /sup 125/I-renin, approximately 59 and 11% of the administered /sup 125/I-renin had accumulated in the liver and the kidneys, respectively, and at later time points the /sup 125/I-renin was highly concentrated in these organs. High-performance liquid chromatographic analysis of the liver and kidney extracts demonstrated that /sup 125/I-renin was catabolized by these organs. Biliary excretion of /sup 125/I-renin was negligible. Urinary excretion of /sup 125/I-renin up to 120 min was approximately 2% of the injected dose. We conclude that both the liver and the kidney are responsible for the clearance of circulating renin, with participation of the liver being predominant.

  1. A high-resolution anatomical rat atlas

    PubMed Central

    Bai, Xueling; Yu, Li; Liu, Qian; Zhang, Jie; Li, Anan; Han, Dao; Luo, Qingming; Gong, Hui

    2006-01-01

    This paper reports the availability of a high-resolution atlas of the adult rat. The atlas is composed of 9475 cryosectional images captured in 4600 × 2580 × 24-bit TIFF format, constructed using serial cryosection-milling techniques. Cryosection images were segmented, labelled and reconstructed into three-dimensional (3D) computerized models. These images, 3D models, technical details, relevant software and further information are available at our website, http://vchibp.vicp.net/vch/mice/. PMID:17062027

  2. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles. PMID:27651859

  3. Characterizing a Rat Brca2 Knockout Model

    DTIC Science & Technology

    2007-05-01

    this treatment (Figure 2b). Aspermatogenesis Meiosis in Brca2/ rats proceeds normally through leptotene and early zygotene (Figure 3a) with 40...Zygotene Late Zygotene Scp3Scp3 Scp3 Scp3 Scp1 CREST CRESTCREST Merge a b Figure 3 (a) Meiosis in Brca2/ spermatocytes does not progress beyond late...control of noncrossover and crossover recombination during meiosis . Cell 106: 47–57. Barlow C, Liyanage M, Moens PB, Tarsounas M, Nagashima K, Brown K

  4. Proteomic profiling of the rat hypothalamus

    PubMed Central

    2012-01-01

    Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE) profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D) gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis. PMID:22519962

  5. Transgenic Rat Models for Breast Cancer Research

    DTIC Science & Technology

    1999-10-01

    Introduction 6 6. Body 9 7. Key Research Accomplishments 15 8. Reportable Outcomes 15 9. Conclusions 16 10. References 17 11. Bibliography 20 12. Personnel 20...seen in human breast cancer (2-4). Third, a high percentage of the resulting rat mammary cancers are hormonally responsiveness, closely mimicking that...13, 17), activated c-neu (18-20), wild type c-neu (21), deregulated growth hormone (22), and deregulated transforming growth factor a (23-25) has

  6. Oxalic acid decreases calcium absorption in rats.

    PubMed

    Weaver, C M; Martin, B R; Ebner, J S; Krueger, C A

    1987-11-01

    Calcium absorption from salts and foods intrinsically labeled with 45Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO3 and CaCl2 than from CaC2O4 (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

  7. Facial Indicators of Positive Emotions in Rats

    PubMed Central

    Finlayson, Kathryn; Lampe, Jessica Frances; Hintze, Sara; Würbel, Hanno; Melotti, Luca

    2016-01-01

    Until recently, research in animal welfare science has mainly focused on negative experiences like pain and suffering, often neglecting the importance of assessing and promoting positive experiences. In rodents, specific facial expressions have been found to occur in situations thought to induce negatively valenced emotional states (e.g., pain, aggression and fear), but none have yet been identified for positive states. Thus, this study aimed to investigate if facial expressions indicative of positive emotional state are exhibited in rats. Adolescent male Lister Hooded rats (Rattus norvegicus, N = 15) were individually subjected to a Positive and a mildly aversive Contrast Treatment over two consecutive days in order to induce contrasting emotional states and to detect differences in facial expression. The Positive Treatment consisted of playful manual tickling administered by the experimenter, while the Contrast Treatment consisted of exposure to a novel test room with intermittent bursts of white noise. The number of positive ultrasonic vocalisations was greater in the Positive Treatment compared to the Contrast Treatment, indicating the experience of differentially valenced states in the two treatments. The main findings were that Ear Colour became significantly pinker and Ear Angle was wider (ears more relaxed) in the Positive Treatment compared to the Contrast Treatment. All other quantitative and qualitative measures of facial expression, which included Eyeball height to width Ratio, Eyebrow height to width Ratio, Eyebrow Angle, visibility of the Nictitating Membrane, and the established Rat Grimace Scale, did not show differences between treatments. This study contributes to the exploration of positive emotional states, and thus good welfare, in rats as it identified the first facial indicators of positive emotions following a positive heterospecific play treatment. Furthermore, it provides improvements to the photography technique and image analysis for the

  8. Radiation-induced heart disease in rats

    SciTech Connect

    Lauk, S.; Kiszel, Z.; Buschmann, J.; Trott, K.R.

    1985-04-01

    After local irradiation of the rat heart with X ray doses of over 10 Gy (single dose), animals developed symptoms of radiation-induced heart disease, which at higher doses would lead to fatal cardiac failure. The LD 50 at 1 year was between 15 Gy and 20 Gy. The pericardium and epicardium responded to irradiation with exudative pericarditis after 4 months. Focal myocardial damage was secondary to progressive capillary damage.

  9. [Cycloferon in treating duodenal ulcers in rats].

    PubMed

    Bul'on, V V; Khnychenko, L K; Sapronov, N S; Kuznetsova, N N; Anikin, V B; arinenko, R Iu; Kovalenko, A L; Alekseeva, L E

    2001-01-01

    The possibility of using cycloferon (interferon inductor) for a complex treatment (in combination with the main drug solcoseryl possessing pronounced therapeutic properties) of duodenum ulcers was experimentally studied in male rats. The experiments showed a considerable difference in the interferon status of animals with model duodenum ulcers treated with cycloferon, solcoseryl, their combination, and placebo (control). The healing effect of solcoseryl administered in combination with cycloferon exceeded that of each component administered separately.

  10. Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

    SciTech Connect

    Thanos, P.K.; Wang, G.; Thanos, P.K..; Kim, R.; Cho, J.; Michaelides, M.; Anderson, B.J.; Primeaux, S.D.; Bray, G.A.; Wang, G.-J.; Robinson, J.K.; Volkow, N.D.

    2010-12-01

    Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.

  11. Photoperiodicity in the male albino laboratory rat.

    PubMed

    Wallen, E P; Turek, F W

    1981-01-29

    Animals inhabiting areas where there are drastic changes in the environment often reproduce only during limited time periods to ensure that young are raised in optimal environmental conditions. The lack of a well defined breeding season in many domesticated animals, presumably because the selective pressures for seasonal breeding have been minimized, suggests that the neuroendocrine events controlling seasonal cyclicity have been bred out of these animals. Little is known about the underlying neuroendocrine changes which may occur during the evolution of a species from a seasonal to a nonseasonal breeder. Whereas the changing photoperiod is the primary environmental cue which initiates and/or terminates the reproductive season in many animals, this is not so in the albino rat Rattus norvegicus, a model nonseasonal breeder. Nevertheless, daylength can influence various reproductive parameters in laboratory rats, suggesting that some of the neuroendocrine components that controlled seasonal breeding previously are still extant in this species. To test this hypothesis, we investigated the effect of daylength on the responsiveness of the neuroendocrine--gonadal axis to the negative-feedback effects of testosterone. This paradigm was chosen because of the important role played by photic-induced changes in steroid feedback sensitivity in the control of seasonal reproduction. We report here that although daylength has very little effect on neuroendocrine--gonadal function in the intact male laboratory rat, it seems that some component(s) of a photoperiodic system involving the pineal gland has been preserved.

  12. Trace element distribution in the rat cerebellum

    SciTech Connect

    Kwiatek, W.M.; Long, G.J.; Pounds, J.G.; Reuhl, K.R.; Hanson, A.L.; Jones, K.W.

    1989-10-01

    Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with x-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and non-destructive irradiation. Trace elements were measured in thin rat brain sections of 20-micrometers thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppM wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semi-quantitative mapping of the TE distribution in a section were used.

  13. Growth hormone aggregates in the rat adenohypophysis

    NASA Technical Reports Server (NTRS)

    Farrington, M.; Hymer, W. C.

    1990-01-01

    Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro.

  14. Deformation-based brain morphometry in rats.

    PubMed

    Gaser, Christian; Schmidt, Silvio; Metzler, Martin; Herrmann, Karl-Heinz; Krumbein, Ines; Reichenbach, Jürgen R; Witte, Otto W

    2012-10-15

    Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra-high field dedicated animal MRI systems. Here, we developed a novel deformation-based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of-interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats.

  15. Bone healing under experimental anemia in rats.

    PubMed

    Giglio, M J; Gorustovich, A; Guglielmotti, M B

    2000-01-01

    The effects of anemia on different physiological parameters have been the object of permanent study. There are no studies in the literature on the effects of this disorder on the process on bone healing. The aim of the present study was to evaluate, histologically and histomorphometrically, the process of osteogenesis in the post-extraction alvcolus of the lower molar, and in the peri-implant environment of rats. Twenty male Wistar rats (body weight (b.w.): 60 +/- 7 g) were grouped into two experimental sets. The control group (n:10) was given 0.5 mL saline solution i.p. The anemic group (n:10) was injected with 6 mg/100 g of b.w. or 3 mg/100 g b.w. phenylhidrazine, a well known hemolytic agent. Under ketamine-xylazine anesthesia the rats were submitted to extraction of the first lower molars, and to implantation in the tibia in keeping with the "laminar test" procedure. Other parameters, i.e. body weight (b.w.), food intake (FI), hematocrit (Htc), and hemoglobinemia (Hb) were monitored every 48 hs. The results showed a reduction in b.w., FI, Htc and Hb in the experimental group. The histological and histomorphometrical data show that the condition of anemia affects osteogenesis quali-quantitatively in the post-extraction alveolus and peri-implant microenvironment. Both bone reparative situations showed that ostegenesis is "sensitive" to anemia and/or the associated conditions, causing a delay in bone healing.

  16. Metabolism of the lignan dehydrodiisoeugenol in rats.

    PubMed

    Li, Fei; Yang, Xiu-Wei

    2011-10-01

    Dehydrodiisoeugenol (DDIE), a major active lignan from the seed and aril of the fruit of Myristica fragrans Houtt., functions as a potential anti-inflammatory agent by inhibiting lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages. However, the metabolism of DDIE remains unknown. This report describes the metabolic fate of DDIE in liver microsomes, urine, and feces of rats treated with DDIE. DDIE metabolites were isolated by sequential column chromatography and high-performance liquid chromatography from liver microsomes incubations, urine, and feces. Nine metabolites ( M-1 to M-9), including 5 new metabolites, were determined spectroscopically using ultra-violet (UV), mass spectrometry (MS), nuclear magnetic resonance (NMR), and circular dichroism (CD). Analysis of the isolated metabolites showed that DDIE undergoes four major pathways of metabolism in the rat: oxidation (including hydroxylation, hydroformylation, and acetylation), demethylation, ring-opening, and dehydrogenation. In contrast to the metabolites from liver microsomes, the major metabolites In vivo were generated from DDIE by multiple metabolic reactions. Given these results, we describe a metabolic pathway for DDIE in the rat that gives insight into the metabolism of DDIE and the mechanism of DDIE bioactivity in humans.

  17. Effects of optimism on motivation in rats.

    PubMed

    Rygula, Rafal; Golebiowska, Joanna; Kregiel, Jakub; Kubik, Jakub; Popik, Piotr

    2015-01-01

    In humans, optimism is a cognitive construct related to motivation; optimists exert effort, whereas pessimists disengage from effort. In this study, using a recently developed ambiguous-cue interpretation (ACI) paradigm we took the unique opportunity to investigate whether "optimism" as a trait is correlated with motivation in rodents. In a series of ACI tests (cognitive bias screening, CBS), we identified rats displaying "pessimistic" and "optimistic" traits. Subsequently, we investigated the trait differences in the motivation of these rats to gain reward and to avoid punishment using a progressive ratio (PR) schedule of reinforcement paradigm. Although "optimistic" and "pessimistic" animals did not differ in their motivation to avoid punishment, the "optimistic" rats were significantly more motivated to gain reward than their "pessimistic" conspecifics. For the first time, we showed an association between cognitive judgment bias and motivation in an animal model. Because both investigated processes are closely related to mental health and wellbeing, our results may be valuable for preclinical modeling of many psychiatric disorders.

  18. Calcium deficiency cannot induce obesity in rats.

    PubMed

    Paradis, S; Cabanac, M

    2005-06-30

    If intake of a required nutrient--here calcium--affects body weight, the effect must be mediated by a change in the body weight set-point. Thus, the controversial 'anti-obesity' influence of high calcium intake should decrease the body weight set-point. Diets differing in calcium content were assigned to three groups of rats. The effects of the diets on body weight, BMI, fat content, plasma calcium, body weight set-point, food intake, and preference for various calcium solutions were measured after 6 weeks of calcium deprivation or supplementation, and again after a further 6 weeks of recovery on a regular diet. After 6 weeks, the low-calcium diet had induced calcium deficiency but had failed to raise the body weight set-point. Nor had it produced obesity or fat accumulation. After 6 weeks of recovery, body weight and fat content were no higher in calcium-deprived rats than in the control or supplemented rats. In this experiment, low-calcium intake failed to cause obesity and did not raise the body weight set-point. The results indicate that calcium intake probably does not affect body weight.

  19. Laser scattering by transcranial rat brain illumination

    NASA Astrophysics Data System (ADS)

    Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

    2012-06-01

    Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

  20. Parathyroid autotransplantation in rats having hypoparathyroidism

    PubMed Central

    Erikoglu, Mehmet; Colak, Bayram; Toy, Hatice; Gurbilek, Mehmet

    2015-01-01

    Re-implantation techniques of extracted parathyroid tissue were developed in order to prevent temporary hypocalcemia. During thyroid surgery; inadvertently removed or devascularized parathyroid gland is usually implanted in the sternocleidomastoid muscle. In this experimental study using rats with hypoparathyroidism, our aim was to investigate whether the excised parathyroid tissue could be seeded in the liver and in the peritoneum, instead of the SCM muscle. In our study, four different groups, each consisting of 10 Wistar albino rats were used (Control group, sternocleidomastoid muscle group, liver group, peritoneum group). Parathyroidectomy was performed and the parathyroid tissue was seeded into the sternocloid mastoid muscle, liver and peritoneum. After 14 days, the rats were sacrificed and levels of calcium, magnesium, phosphorus, alkaline phosphatase and parathyroid hormone were measured in rats’ blood samples. The autotransplanted parathyroid tissue was then excised and examined. In all groups, parathyroid tissues were analyzed histopathologically according to calcification, necrosis, tissue loss, foreign body reaction, inflammation and fibrosis. Regarding Ca, Mg, PO4, ALP; There were no difference between the groups. When we compared control group with the other groups; a difference was observed in the levels of PTH (P<0.05). In pathological examination; regarding tissue loss; there was a difference between liver and peritoneum groups (P<0.05). In our study, we expected better result in plantings inside liver and peritone compared to SKM. However, there were no difference between the groups. PMID:26629152

  1. Pulmonary toxicity of thioureas in the rat

    SciTech Connect

    Scott, A.M.; Powell, G.M.; Curtis, C.G. ); Upshall, D.G. )

    1990-04-01

    Administration of {alpha}-naphthylthiourea (ANTU) to rats causes damage to pulmonary endothelial cells and possibly mesothelial lining cells that together may account for the massive pleural effusion characteristic of thiourea toxicity. Using {sup 35}S-thiourea as a model compound, the extent of binding of {sup 35}S to lung proteins correlated well with the extent of edema, suggesting that the extent of binding of thiourea metabolites is a measure of lung toxicity. ANTU and phenylthiourea (PTU) compete for {sup 35}S binding to lung slices, suggesting that these toxins may act in a similar way. Binding of {sup 35}S in lung slices from resistant rats is much less than in controls, and resistance cannot be explained by differences in either whole body metabolism or redistribution of thiourea in vivo. Lung glutathione levels (in vitro and in vivo) in normal and resistant rats following thiourea administration were essentially the same. However, at doses of thiourea that cause pleural effusion, there was an increase in total lung glutathione.

  2. Antihyperglycaemic effect of Mangifera indica in rat.

    PubMed

    Aderibigbe, A O; Emudianughe, T S; Lawal, B A

    1999-09-01

    The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded.

  3. Neurofilament expression in cultured rat adenohypophysial cells.

    PubMed

    Quintanar, J L; Salinas, E

    2001-01-01

    The aim of the present work was to investigate in cultured rat adenohypophysial cells: a) the presence of neurofilaments of 200 kDa (NF-H), b) the effect of thyroid hormone (T(3)) and thyrotropin releasing hormone (TRH) on the expression of NF-H and c) the possible role of NF-H on thyrotropin (TSH) secretion. The presence of NF-H was observed by immunocytochemistry in cultured rat adenohypophysial cells. The exposure to T(3) for 12 h produced a significant increase in NF-H expression; whereas incubation with TRH or T(3)+TRH resulted in no change. The cells treated with T(3) or TRH or T(3)+TRH for 24 h showed no alteration. However, incubation for 48 h with TRH or T(3)+TRH caused significant decrease in NF-H expression. Incubation with NF-H antibodies produced a significant inhibition of calcium-induced TSH release in digitonin-permeabilized adenohypophysial cells. These results provide evidence that NF-H is present in cultured rat adenohypophysial cells, and that T(3) and TRH can modify NF-H expression. It can be suggested that in cultured adenohypophysial cells, NF-H may play a role in the secretory process.

  4. Forced swim test behavior in postpartum rats.

    PubMed

    Craft, R M; Kostick, M L; Rogers, J A; White, C L; Tsutsui, K T

    2010-10-01

    This study was undertaken to determine whether depression-like behavior can be observed in gonadally intact females that have experienced normal pregnancy. When tested on the forced swim test (FST) on postpartum days 1-7, previously pregnant rats spent slightly more time immobile, significantly less time swimming and diving, and defecated more than virgin controls. Subchronic treatment with nomifensine (DA reuptake inhibitor, 2.5mg/kg) but not sertraline (serotonin reuptake inhibitor, 10mg/kg) or desipramine (norepinephrine reuptake inhibitor, 10mg/kg) significantly decreased immobility on postpartum day 2. In rats pre-exposed to the FST in mid-pregnancy, neither subchronic nor chronic treatment with desipramine or sertraline decreased immobility on postpartum day 2; in contrast, chronic desipramine significantly decreased immobility in virgin controls. These results indicate that postpartum female rats, compared to virgin controls, show a reduction in some "active coping behaviors" but no significant increase in immobility when tested during the early postpartum period, unlike ovariectomized females that have undergone hormone-simulated pregnancy (HSP). Additionally, immobility that is increased by FST pre-exposure is not readily prevented by treatment with standard antidepressant medications in postpartum females. Depression-like behaviors previously observed in females that have undergone HSP may result from the more dramatic changes in estradiol, prolactin or corticosterone that occur during the early "postpartum" period, compared to the more subtle changes in these hormones that occur in actual postpartum females.

  5. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

    PubMed

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A; Yaylali, Asl; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments.

  6. Postprandial hemodynamics in the conscious rat

    SciTech Connect

    Anzueto Hernandez, L.; Kvietys, P.R.; Granger, D.N.

    1986-07-01

    The postprandial intestinal hyperemia was studied in conscious and anesthetized rats using the radioactive microsphere technique. Carbohydrate, protein, lipid, and mixed meals, and the vehicle (Tyrode's solution), were placed in the stomach via a gastrostomy tube. In conscious rats, blood flow increased by 40-80% in the duodenum and jejunum 1 h after either a carbohydrate, lipid, protein, or mixed meal. Tyrode's solution produced a comparable hyperemia. Blood flow in the distal bowel segments (ileum, cecum, and colon) was significantly increased only by Tyrode's solution and the carbohydrate meal. The proximal intestinal hyperemia produced by the mixed meal in conscious animals was significantly attenuated by vagotomy yet unaltered by atropine pretreatment. In contrast to the results obtained from conscious rats, the mixed meal did not significantly alter intestinal blood flow in anesthetized animals. The results of this study indicate that the postprandial intestinal hyperemia is much greater in conscious than anesthetized animals. This difference may result from the higher resting blood flows in the latter group. The hyperemic response in conscious animals may be mediated by the vagus nerve.

  7. INTESTINAL TRIGLYCERIDE ABSORPTION IN THE RAT

    PubMed Central

    Cardell, Robert R.; Badenhausen, Susan; Porter, Keith R.

    1967-01-01

    This report provides information on the morphology of fat absorption in rat intestinal epithelial cells. Three types of experiments were performed: (a) intubation of corn oil into fasted rats, (b) injection of physiological fatty-chyme prepared from fat-fed donor rats into ligated segments of jejunum of fasted animals, and (c) administration of electron-opaque particles in corn oil and markers given concurrently with the fat. These results support the hypothesis that fat is absorbed by selective diffusion of monoglycerides and fatty acids from micelles rather than by pinocytosis of unhydrolized triglycerides. Evidence is presented that the pits between the microvilli, previously believed to function in the transport of fat, are not involved in this process. Instead they appear to contribute their contents to lysosomes in the apical cytoplasm. Arguments are offered that the monoglycerides and fatty acids diffuse from the micelle while the latter is associated with the microvillous membrane of the absorptive cell. These micellar components penetrate the plasma membrane and diffuse into the cytoplasmic matrix where they encounter the SER. Triglyceride synthesis occurs in the SER and results in the deposition of fat droplets within its lumina. The synthesis of triglycerides and their sequestration into the SER establishes an inward diffusion gradient of monoglycerides and fatty acids. PMID:6033529

  8. Alterations of reward mechanisms in bulbectomised rats.

    PubMed

    Grecksch, Gisela; Becker, Axel

    2015-06-01

    The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature. The voluntary ethanol intake was increased significantly in bulbectomised rats in a drinking experiment and also after a period of abstinence. Conditioned place preference (CPP) was induced in all animals. However, bulbectomised rats needed a higher dose of alcohol to produce CPP. The sedative effect of ethanol on locomotor activity was reduced in bulbectomised animals. Measurement of body temperature revealed a dose-dependent hypothermic effect of ethanol in both groups. These results suggest that the reward mechanisms may be altered in this animal model as a common phenomenon associated with depression. Furthermore, they support the hypothesis that the addictive and/or rewarding properties of some drugs of abuse may be modified in depression.

  9. Ethanol and blood pressure in rats

    SciTech Connect

    Hatton, D.C.; Edgar, S.; McCarron, D.A. )

    1989-02-09

    Epidemiologists have identified alcohol as a risk factor in hypertension. Attempts to increase blood pressure in rats with chronic alcohol ingestion have met with mixed results. Some investigators have reported increases in blood pressure while others have reported decreases. Most investigators have given alcohol in the drinking water which produced differences in food intake across groups. To control for food intake, Wister rats were simultaneously pair fed a liquid diet with either ethanol as 35% of calories or a control diet using ARF/Israel pair-feeding devices. At 5 weeks of age, animals on ethanol diets had lower systolic blood pressure than control animals (145 (n-19) vs. 121 (n-19) mmHg). There was no difference in weight between ethanol and control animals. The same pattern of results was apparent at 7 weeks (143 (n-13) vs. 119 (n-13) mmHg) and 9 weeks (147 (n-7) vs. 124 (n-7)). The data indicate that ethanol produces hypotension in rats when food intake is controlled.

  10. Solcoseryl stimulates behavioural activity of rats.

    PubMed

    Braszko, J J; Winnicka, M M; Wiśniewski, K

    1996-01-01

    The influence of Solcoseryl (S), a protein-free extract of calves' blood given intraperitoneally (i.p.) on the behavioural measures of activity of the central nervous system of male Wistar rats was examined. The drug (1.0 ml/kg i.p.) given 60 min before testing the animals in electromagnetic motimeter significantly enhanced overall and vertical motility of rats. S at the doses of 0.5, 1.0 and 2.0 ml/kg did not significantly influence the activity of rats in "open field". 1.0 ml/kg of S given 15, 45 and 60 min before thiopental (30 mg/kg i.p.) did not change the onset and time of sleep following the latter drug, except for the significant shortening of the time of sleep of animals injected with S 15 min before thiopental. S at the dose of 1.0 ml/kg did not change stereotypies produced by apomorphine (2.0 mg/kg i.p.) and amphetamine (6.5 mg/kg i.p.) but decreased intensity of haloperidol (1.0 mg/kg i.p.) catalepsy.

  11. [Effects of human and rat interferons-alpha on the behavior of rats of different ages. Comparative study of the homology of amino acid sequences].

    PubMed

    Loseva, E V; Loginova, N A; Nekliudov, V V; Mats, V N; Kurskaia, O V; Pasikova, N V

    2009-01-01

    Effects of chronic intranasal administration of human and rat interferons alpha on feeding and defensive behavior of rats were studied. Natural leukocyte human interferon "Lokferon" (a mixture of alpha interferon subtypes) and recombinant rat interferon alpha of the first subtype were used in the dose of 350 ME per rat daily. In addition, using the databases NCBI and EBI, we quantitatively estimated homology of amino-acid sequences between different subtypes of human and rat interferons. Both human (mostly in young rats) and rat interferons (mostly in old rats) increased rat feeding behavior after food conditioning to an audio tone. In old (but not in young) rats, both human and rat interferons worsened the ability of time interval assessment. In young (but not old) rats, both interferon kinds improved avoidance conditioning. The degree of homology between different human and rat interferons varied from 72% to 77%. Thus, generally, the effects of rat and human alpha interferons (350 ME) on rat conditioning were similar. This may be due to high degree of homology of amino-acid sequences between the two interferons.

  12. Rats socially-reared and full fed learned an autoshaping task, showing less levels of fear-like behaviour than fasted or singly-reared rats.

    PubMed

    Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia

    2004-07-01

    During the learning of instrumental tasks, rats are usually fasted to increase reinforced learning. However, fasting produces several undesirable side effects. The aim of this study was to test the hypothesis that control rats, i.e. full-fed and group-reared rats, will learn an autoshaping task to the same level as fasted or singly-reared rats. The interaction between fasting and single-rearing of rats was also tested. Results showed that control rats and fasted rats acquired the autoshaping task similarly, independently of rearing condition or gender. However, fasted or singly-reared rats produced fear-like behaviour, since male rats group-reared and fasted (85% body/wt, P <0.05), male rats singly-reared (full fed, P <0.05; 12 h fasted, P <0.05; 85% body/wt, P <0.05), female rats group-reared (12 h fasted, P <0.05; 85% body/wt, P <0.05) and female rats singly reared (full fed, P <0.05; 12 h fasted, P <0.05; 85% body/wt, P <0.05) displayed reduced amounts of time exploring the open arms of the elevated plus-maze. In conclusion, control rats learned the autoshaping task to the same level as fasted or singly-reared rats. However, fasting or single-rearing produced fear-like behaviour. Thus, the training of control rats in autoshaping tasks may be an option that improves animal welfare.

  13. Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

    PubMed

    Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

    2015-03-01

    The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD.

  14. Rat hepatitis E virus derived from wild rats (Rattus rattus) propagates efficiently in human hepatoma cell lines.

    PubMed

    Jirintai, Suljid; Tanggis; Mulyanto; Suparyatmo, Joseph Benedictus; Takahashi, Masaharu; Kobayashi, Tominari; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2014-06-24

    Although rat hepatitis E virus (HEV) has been identified in wild rats, no cell culture systems for this virus have been established. A recent report suggesting the presence of antibodies against rat HEV in human sera encouraged us to cultivate rat HEV in human cells. When liver homogenates obtained from wild rats (Rattus rattus) in Indonesia were inoculated onto human hepatocarcinoma cells, the rat HEV replicated efficiently in PLC/PRF/5, HuH-7 and HepG2 cells, irrespective of its genetic group (G1-G3). The rat HEV particles released from cultured cells harbored lipid-associated membranes on their surface that were depleted by treatment with detergent and protease, with the buoyant density in sucrose shifting from 1.15-1.16 g/ml to 1.27-1.28 g/ml. A Northern blotting analysis revealed genomic RNA of 7.0 kb and subgenomic RNA of 2.0 kb in the infected cells. The subgenomic RNA of G1-G3 each possessed the extreme 5'-end sequence of GUAGC (nt 4933-4937), downstream of the highly conserved sequence of GAAUAACA (nt 4916-4923). The establishment of culture systems for rat HEV would allow for extended studies of the mechanisms of viral replication and functional roles of HEV proteins. Further investigation is required to clarify the zoonotic potential of rat HEV.

  15. Rickettsial pathogens in the tropical rat mite Ornithonyssus bacoti (Acari: Macronyssidae) from Egyptian rats (Rattus spp.).

    PubMed

    Reeves, Will K; Loftis, Amanda D; Szumlas, Daniel E; Abbassy, Magda M; Helmy, Ibrahim M; Hanafi, Hanafi A; Dasch, Gregory A

    2007-01-01

    We collected and tested 616 tropical rat mites (Ornithonyssus bacoti (Hirst)) from rats (Rattus norvegicus (Berkenhout) and R. rattus (Linnaeus)) throughout 14 governorates in Egypt and tested DNA extracts from pools of these mites for Bartonella spp., Coxiella burnetii, and Rickettsia spp. by PCR amplification and sequencing. Three different mite-associated bacterial agents, including one Bartonella and two Rickettsia spp., were detected in eight pools of mites. Further research could demonstrate the vector potential of mites and pathogenicity of these agents to humans or animals.

  16. Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s

    SciTech Connect

    Pechurskaya, Tatiana A. . E-mail: usanov@iboch.bas-net.by

    2007-02-16

    The interaction of adrenodoxin (Adx) and NADPH cytochrome P450 reductase (CPR) with human microsomal steroidogenic cytochrome P450s was studied. It is found that Adx, mitochondrial electron transfer protein, is able to support reactions catalyzed by human microsomal P450s: full length CYP17, truncated CYP17, and truncated CYP21. CPR, but not Adx, supports activity of truncated CYP19. Truncated and the full length CYP17s show distinct preference for electron donor proteins. Truncated CYP17 has higher activity with Adx compared to CPR. The alteration in preference to electron donor does not change product profile for truncated enzymes. The electrostatic contacts play a major role in the interaction of truncated CYP17 with either CPR or Adx. Similarly electrostatic contacts are predominant in the interaction of full length CYP17 with Adx. We speculate that Adx might serve as an alternative electron donor for CYP17 at the conditions of CPR deficiency in human.

  17. Genotoxicity of nimesulide in Wistar rats.

    PubMed

    Borkotoky, Debojyoti; Panda, Sushen K; Sahoo, Gyana R; Parija, Subas C

    2014-04-01

    It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects because these were in use before the local regulations were enforced. According to the material safety database, the toxicological effect of nimesulide is not yet fully understood. The present study therefore aimed to explore the genotoxic potential of nimesulide in Wistar albino rats. Nimesulide at the dose level of 50 (Gr-50), 100 (Gr-100) and 200 (Gr-200) mg/kg body weight (b.w.) was given orally. Each rat in treated groups (Gr-50 to Gr-200; n = 10) and negative control group (Gr-NC; n = 10) were administered orally (p.o.) with nimesulide and normal saline, respectively, for 14 days. Similarly, rats of positive control (Gr-PC; n = 10) were administered with cyclophosphamide (CPA; 20 mg/kg b.w.) intraperitoneally. CPA served as positive control, whereas normal saline served as as negative control. Approximately 1-2 mL of blood was collected from retro-orbital sinus for comet assay and subsequently rats were sacrificed to aspirate the femoral bone marrow for the micronucleus test. Structural chromosomal aberration, micronucleated polychromatic erythrocytes (MnPCEs), polychromatic erythrocytes (PCEs) and comet tail length were calculated using micronucleus assay and comet assay, respectively, which served as markers of genotoxicity. In the present study, it was observed that a significant increase in (1) different classified structural chromosomal aberrations with increase in nimesulide dose, such as gaps (50 mg/kg), gaps, breaks and pulverizations (100 mg/kg) and gaps, breaks, fragments, rings and pulverizations (200 mg/kg) and (2) % MnPCE and comet tail length was observed in animals treated with CPA (p < 0.001) or 200 mg of nimesulide (p < 0.05), as compared to negative control. In conclusion, nimesulide (200 mg/kg b.w.) produced a

  18. Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.

    PubMed

    Arkadopoulos, N; Lilja, H; Suh, K S; Demetriou, A A; Rozga, J

    1998-11-01

    To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic. Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic. Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01). Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic.

  19. Variable reactive hyperemia in normotensive strains of rat.

    PubMed

    Heimlich, J Brett; Pollock, David M

    2014-06-18

    Previous studies from our laboratory report variation in nitric oxide (NO)-dependent arterial pressure within the same strain of normotensive Sprague-Dawley rat dependent upon the commercial vendor supplying the rats. Clinical assessment of endothelial NO activity and endothelial function in general has used postocclusion, flow-mediated dilation (FMD). Therefore, this study was conducted to determine whether the reactive hyperemic response was different between two normotensive strains from two different suppliers, Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats from Charles River (CR) and Harlan Laboratories (H), respectively. Rats were anesthetized and the femoral artery was occluded for 5 min, with femoral blood flow measured continuously by use of an ultrasonic perivascular flow probe. The average area under the reactive hyperemic response curve (3-min duration) was not different between SD rats from CR (80 ± 23 mL/min∙s; n = 6) and H (94 ± 16 mL/min∙s; n = 6). As previously reported, blood pressures were higher in the SD rats from H versus CR. WKY rats from both suppliers had significantly larger hyperemia; 371 ± 67 versus 281 ± 71 mL/min∙s (n = 5) for the CR and H WKY rats, respectively, but again, were not different between vendors. Blood pressures in WKY rats were similar between vendors. These results suggest that differences in NO bioactivity are not discernable with an adapted FMD protocol in the rat and that normotensive strains of rat can have large differences in reactive hyperemia despite having similar blood pressures.

  20. Variable reactive hyperemia in normotensive strains of rat

    PubMed Central

    Heimlich, J. Brett; Pollock, David M.

    2014-01-01

    Abstract Previous studies from our laboratory report variation in nitric oxide (NO)‐dependent arterial pressure within the same strain of normotensive Sprague–Dawley rat dependent upon the commercial vendor supplying the rats. Clinical assessment of endothelial NO activity and endothelial function in general has used postocclusion, flow‐mediated dilation (FMD). Therefore, this study was conducted to determine whether the reactive hyperemic response was different between two normotensive strains from two different suppliers, Sprague–Dawley (SD) and Wistar–Kyoto (WKY) rats from Charles River (CR) and Harlan Laboratories (H), respectively. Rats were anesthetized and the femoral artery was occluded for 5 min, with femoral blood flow measured continuously by use of an ultrasonic perivascular flow probe. The average area under the reactive hyperemic response curve (3‐min duration) was not different between SD rats from CR (80 ± 23 mL/min∙s; n = 6) and H (94 ± 16 mL/min∙s; n = 6). As previously reported, blood pressures were higher in the SD rats from H versus CR. WKY rats from both suppliers had significantly larger hyperemia; 371 ± 67 versus 281 ± 71 mL/min∙s (n = 5) for the CR and H WKY rats, respectively, but again, were not different between vendors. Blood pressures in WKY rats were similar between vendors. These results suggest that differences in NO bioactivity are not discernable with an adapted FMD protocol in the rat and that normotensive strains of rat can have large differences in reactive hyperemia despite having similar blood pressures. PMID:24944292

  1. Impaired NaCl taste thresholds in Zn deprived rats

    SciTech Connect

    Brosvic, G.M.; Slotnick, B.M.; Nelson, N.; Henkin, R.I.

    1986-03-05

    Zn deficiency is a relatively common cause of loss of taste acuity in humans. In some patients replacement with exogenous Zn results in rapid reversal of the loss whereas in others prolonged treatment is needed to restore normal taste function. To study this 300 gm outbred Sprague Dawley rats were given Zn deficient diet (< 1 ppm Zn) supplemented with Zn in drinking water (0.1 gm Zn/100 gm body weight). Rats were trained in an automated operant conditions procedure and NaCl taste thresholds determined. During an initial training period and over two replications mean thresholds were 0.006% and mean plasma Zn was 90 +/- 2 ..mu..g/dl (M +/- SEM) determined by flame atomic absorption spectrophotometry. Rats were then divided into two groups; in one (3 rats) Zn supplement was removed, in the other (4 rats), pair-fed with the former group, Zn supplement was continued. In 10 days NaCl thresholds in Zn deprived rats increased significantly (0.07%, p < 0.01) and in 17 days increased 13 fold (0.08%) but thresholds for pair fed, supplemented rats remained constant (0.006%). There was no overlap in response between any rat in the two groups. Plasma Zn at 17 days in Zn-deprived rats was significantly below pair-fed rats (52 +/- 13 vs 89 +/- 6 ..mu..g/dl, respectively, P < 0.01). At this time Zn-deprived rats were supplemented with Zn for 27 days without any reduction in taste thresholds. These preliminary results are consistent with previous observations in Zn deficient patients.

  2. Characterization of Rat Meibomian Gland Ion and Fluid Transport

    PubMed Central

    Yu, Dongfang; Davis, Richard M.; Aita, Megumi; Burns, Kimberlie A.; Clapp, Phillip W.; Gilmore, Rodney C.; Chua, Michael; O'Neal, Wanda K.; Schlegel, Richard; Randell, Scott H.; C. Boucher, Richard

    2016-01-01

    Purpose We establish novel primary rat meibomian gland (MG) cell culture systems and explore the ion transport activities of the rat MG. Methods Freshly excised rat MG tissues were characterized as follows: (1) mRNA expression of selected epithelial ion channels/transporters were measured by RT-PCR, (2) localization of epithelial sodium channel (ENaC) mRNAs was performed by in situ hybridization, and (3) protein expression and localization of βENaC, the Na+/K+/Cl− cotransporter (NKCC), and the Na+/K+ ATPase were evaluated by immunofluorescence. Primary isolated rat MG cells were cocultured with 3T3 feeder cells and a Rho-associated kinase (ROCK) inhibitor (Y-27632) for expansion. Passaged rat MG cells were cultured as planar sheets under air-liquid interface (ALI) conditions for gene expression and electrophysiologic studies. Passaged rat MG cells also were cultured in matrigel matrices to form spheroids, which were examined ultrastructurally by transmission electron microscopy (TEM) and functionally using swelling assays. Results Expression of multiple ion channel/transporter genes was detected in rat MG tissues. β-ENaC mRNA and protein were localized more to MG peripheral acinar cells than central acinar cells or ductular epithelial cells. Electrophysiologic studies of rat MG cell planar cultures demonstrated functional sodium, chloride, and potassium channels, and cotransporters activities. Transmission electron microscopic analyses of rat MG spheroids revealed highly differentiated MG cells with abundant lysosomal lamellar bodies. Rat MG spheroids culture-based measurements demonstrated active volume regulation by ion channels. Conclusions This study demonstrates the presence and function of ion channels and volume transport by rat MG. Two novel primary MG cell culture models that may be useful for MG research were established. PMID:27127933

  3. The effect of dietary pyridoxine on arsenic deprivation in rats

    SciTech Connect

    Uthus, E.O.; Poelllot, R. )

    1991-03-15

    In experiments on As deprivation, many findings indicate that As can affect enzymes or metabolites that are also influenced by vitamin B{sub 6}. Thus, an experiment was designed to ascertain the effect of pyridoxine (pyr) on As deprivation in rats. Male, weanling rats were fed an amino acid based diet containing 0.24% methionine (M) and less than 15 ng As/g. Dietary variables were As, 0 or 1 {mu}g/g; M, 0 or 3 g/kg; and pyridoxine, 0 or 10 mg/kg. After 10 weeks, growth was reduced by As, Pyr, or M deprivation. Both endogenous ({minus}PP) and pyridoxal phosphate-stimulated (+PP) RBC aspartate aminotransferase were decreased by Pyr deficiency. The ratio of +PP/{minus}PP, known as the activation coefficient (AC), was affected by an interaction between As and Pyr. Pyr deficiency resulted in a less marked increase in AC in the As-deprived rats than in the As-supplemented rats. Plasma Fe was slightly decreased by Pyr deficiency in the As-deprived rats but increased by Pyr deficiency in the As-supplemented rats. Plasma threonine and serine were increased by As supplementation in the Pyr-deficient rats but there was no effect of As supplementation in the Pyr-supplemented rats. Plasma alanine was decreased by As or Pyr deprivation. In Pyr deficiency, As deprivation had no effect on plasma glycine (G) in the M-deficient rats but decreased G in the M-supplemented rats. In the Pyr-supplemented rats, As had no effect on G, regardless of M. The findings indicate that As and Pyr interact to affect amino acid metabolism.

  4. Allyl isothiocyanate: comparative disposition in rats and mice

    SciTech Connect

    Ioannou, Y.M.; Burka, L.T.; Matthews, H.B.

    1984-09-15

    Allyl isothiocyanate (AITC), the major component of volatile oil of mustard, was recently reported to induce transitional-cell papillomas in the urinary bladder of male Fischer 344 rats, but not in the bladders of female rats or B6C3F1 mice. The present investigation of comparative disposition in both sexes of each species was designed to detect sex or species differences in disposition which might explain susceptibility to AITC toxicity. AITC was readily cleared from all rat and mouse tissues so that within 24 hrs. after administration less than 5% of the total dose was retained in tissues. The highest concentration of AITC-derived radioactivity was observed in male rat bladder. Clearance of AITC-derived radioactivity by each species was primarily in urine (70 to 80%) and in exhaled air (13 to 15%) with lesser amounts in feces (3 to 5%). Rats excreted one major and four minor metabolites in urine. The major metabolite from rat urine was identified by NMR spectroscopy to be the mercapturic acid N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine. Mice excreted in urine the same major metabolite identified in rat urine as well as three other major and two minor metabolites. Sex-related variations were observed in the relative amounts of these metabolites. Both species excreted a single metabolite in feces. Metabolism of AITC by male and female rats was similar, but female rats excreted over twice the urine volume of male rats. Results of the present study indicate that excretion of a more concentrated solution of AITC metabolite(s) in urine may account for the toxic effects of AITC on the bladder of male rats.

  5. Involvement of aspartoacylase in tremor expression in rats

    PubMed Central

    Nishitani, Ai; Tanaka, Miyuu; Shimizu, Saki; Kunisawa, Naofumi; Yokoe, Mayuko; Yoshida, Yusaku; Suzuki, Toshiro; Sakuma, Tetsushi; Yamamoto, Takashi; Kuwamura, Mitsuru; Takenaka, Shigeo; Ohno, Yukihiro; Kuramoto, Takashi

    2016-01-01

    Essential tremor (ET) is a common movement disorder with a poorly understood etiology. The TRM/Kyo mutant rat, showing spontaneous tremor, is an animal model of ET. Recently, we demonstrated that tremors in these rats emerge when two mutant loci, a missense mutation in the hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (Hcn1) and the tremor (tm) deletion, are present simultaneously. However, we did not identify which gene within the tm deletion causes tremor expression in TRM/Kyo rats. A strong candidate among the 13 genes within the tm deletion is aspartoacylase (Aspa), because some Aspa-knockout mouse strains show tremor. Here, we generated Aspa-knockout rats using transcription activator-like effector nuclease technology and produced Aspa/Hcn1 double-mutant rats by crossing Aspa-knockout rats with Hcn1-mutant rats. The Aspa-knockout rats carried nonsense mutations in exon 4; and ASPA proteins were not detectable in their brain extracts. They showed elevated levels of N-acetyl-L-aspartate (NAA) in urine and spongy vacuolation and abnormal myelination in the central nervous system, but no tremor. By contrast, Aspa/Hcn1 double-mutant rats spontaneously showed tremors resembling those in TRM/Kyo rats, and the tremor was suppressed by drugs therapeutic for ET but not for parkinsonian tremor. These findings indicated that the lack of the Aspa gene caused tremor expression in TRM/Kyo rats. Our animal model suggested that the interaction of NAA accumulation due to ASPA deficiency with an unstable neuronal membrane potential caused by HCN1 deficiency was involved in tremor development. PMID:27026062

  6. Warfarin resistance in a French strain of rats.

    PubMed

    Lasseur, Romain; Longin-Sauvageon, Christiane; Videmann, Bernadette; Billeret, Mikaëline; Berny, Philippe; Benoit, Etienne

    2005-01-01

    A warfarin-resistant strain and a warfarin-susceptible strain of wild rats (Rattus norvegicus) maintained in enclosures of the National Veterinary School of Lyon (France) were studied to determine the mechanism of the resistance to anticoagulant rodenticides. A low vitamin K epoxide reductase (VKOR) activity has been reported for many resistant rat strains. As recently suggested, mutations in the vitamin K epoxide reductase subunit 1 (VKORC1) gene are the genetic basis of anticoagulant resistance in wild populations of rats from various locations in Europe. Here we report, for our strain, one of the seven described mutations (Tyr139Phe) for VKORC1 in rats. In addition, a low expression of mRNA encoding VKORC1 gene is observed in resistant rats, which could explain their low VKOR activity. We calculated kinetic parameters of VKOR in the warfarin-resistant and warfarin-susceptible rats. The V(max) and the K(m) of the VKOR obtained in resistant rats were lowered by 57 and 77%, respectively, compared to those obtained in susceptible rats. As a consequence, the enzymatic efficiency (V(m)/K(m)) of the VKOR was similar between resistant and susceptible rats. This result could be a good explanation to the observation that no clinical signs of vitamin K deficiency was observed in the warfarin-resistant strain, while a low VKOR activity was found. VKOR activity in warfarin-resistant rats was poorly inhibited by warfarin (K(i) for warfarin is 29 microM and 0.72 microM for resistant and susceptible rats, respectively).

  7. Weak and nondiscriminative responses to conspecifics in the rat hippocampus.

    PubMed

    von Heimendahl, Moritz; Rao, Rajnish P; Brecht, Michael

    2012-02-08

    Little is known about how hippocampal neurons in rodents respond to and represent conspecifics. To address this question, we let rats interact while quantifying hippocampal neuronal activation patterns with extracellular recordings and immediate-early gene (c-Fos) expression. A total of 319 single putative pyramidal neurons was recorded in dorsal hippocampus. In sessions with multiple stimulus rats, no cell responded differentially to individual rats (N = 267 cells). We did find, however, that the presence of other rats induced a significant enhancement or suppression of firing in a fraction of neurons (n = 22 of 319; 7%). As expected, a large fraction of neurons (n = 170; 53%) had place fields. There was no evidence for place-independent responses to rats. Rather, the modulations were linked to the spatial responses. While neurons did not discriminate between individual rats, they did discriminate between rats and inanimate objects. Surprisingly, neuronal responses were more strongly modulated by objects than by rats, even though subjects spent more time near their conspecifics. Consistent with the low fraction of rat-modulated cells, social encounters did not induce c-Fos expression in the hippocampus, while there was a social interaction-specific expression in the basolateral amygdala. In both interacting and non-interacting rats, the fraction of c-Fos-expressing cells in the hippocampus was very low. Our investigation of social coding in the rat hippocampus, along with other recent work, showed that social responses were rare and lacked individual specificity, altogether speaking against a role of rodent dorsal hippocampus in social memory.

  8. Blunted central bromocriptine-induced tachycardia in conscious, malnourished rats.

    PubMed

    Lahlou, Saad; Araújo Lima, Paula F; Interaminense, Leylliane F L; Duarte, Gloria Pinto

    2003-04-01

    Bromocriptine-induced tachycardia, persisting after adrenalectomy, is mediated by central dopamine D2 receptor stimulation through activation of the sympathetic outflow to the heart. The present study investigated the effects of malnutrition during pregnancy on bromocriptine-induced tachycardia in adult conscious rats. Malnourished rats were obtained by feeding dams a multideficient diet (providing 8% protein) during mating and pregnancy. Birth weight was significantly reduced in malnourished rats when compared to control rats born to dams fed standard commercially diet (23% protein) during mating and pregnancy. Baseline mean aortic pressure and heart rate in malnourished rats were comparable to those of well-nourished rats. Tachycardia (33+/-9 beats/min.), but not the hypotensive response to intravenous bromocriptine (150 microg/kg) was significantly reduced in malnourished rats, compared with control rats (70+/-10 beats/min.). In malnourished rats, pretreatment with intravenous domperidone (500 microg/kg) blocked the bromocriptine-induced hypotension, without affecting the tachycardia. Neither cardiac vagal (40+/-6 beats/min.) nor sympathetic tone (76+/-6 beats/min.) was significantly altered by multideficient diet-induced malnutrition (51+/-6 and 67+/-10 beats/min., respectively). In isolated perfused heart preparations from malnourished rats, positive inotropic response to isoproterenol (10-8 to 10-4 M) was not significantly different compared to that in control rats. In summary, malnutrition during foetal life blunted the bromocriptine-induced tachycardia, an effect that could be related to central dopamine D2 receptor desensitization rather than to impairment of autonomic regulation of the heart or cardiac beta-adrenoceptor desensitization.

  9. Cell Therapy for Liver Disease Using Bioimaging Rats

    PubMed Central

    Haga, Junko; Enosawa, Shin; Kobayashi, Eiji

    2017-01-01

    Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies. We have developed various kinds of rat imaging models and have evaluated the effect of cell therapy for liver disease. Bone marrow cells (BMCs) of the Alb-DsRed2 rat were transplanted via the portal vein (PV) in acute and chronic liver damage models. The number of Alb-DsRed2+ albumin-producing cells increased, and the size of the cells increased in the chronic liver damage model as well as in the acute liver damage model. Luciferase transgenic (luc-Tg) rat hepatocytes were transplanted into the hepatectomized LEW rat via the PV. Luminescence intensity lasted for 2 months in the hepatectomized rat. BMCs obtained from green fluorescent protein (GFP) Tg rats were transplanted repeatedly via the PV using an implanted catheter with a port. Repeated BMT via the PV reduced the liver fibrosis. Adipocyte-derived MSCs from the luc-Tg rat were transplanted into the hepatectomized rat model via the PV after ischemic reperfusion. MSCs inhibited hepatocyte apoptosis and promoted liver regeneration. Transplanting the optimal number of cells by an effective and safe way is important for clinical application. Bioimaging rats are a powerful tool for cell transplantation research because it makes observation of the in vivo kinetics of transplanted cells possible. Cell transplantation research using bioimaging rats contributes greatly to evaluating effective methods of cell therapy. PMID:28174669

  10. Long-term adrenalectomy causes loss of dentate gyrus and pyramidal neurons in the adult hippocampus.

    PubMed

    Sapolsky, R M; Stein-Behrens, B A; Armanini, M P

    1991-11-01

    A growing literature suggests that the hippocampus can be damaged by glucocorticoids, the adrenal steroids secreted during stress. Thus, considerable interest was generated by recent reports that prolonged elimination of glucocorticoids by adrenalectomy (ADX) damages hippocampal dentate gyrus neurons. To date, this phenomenon has only been observed in rats of peripubertal age or younger; moreover, reports differ considerably as to the magnitude of the damage induced. Therefore, we examined this issue in rats ADXd at 5 months of age. Three months later, there was a significant 26% loss of dentate neurons in a subset of rats. In agreement with these previous reports, this subset had attenuated weight gain and electrolyte imbalances, suggestive of complete removal of the adrenals and accessory adrenal tissue. As a novel observation, we also observed significant (19%) loss of CA4 pyramidal neurons. Thus, both severe under- or overexposure to glucocorticoids can be deleterious to a number of hippocampal neuron types.

  11. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  12. Exercise training attenuates anaphylactic venoconstriction in rat perfused liver, but does not affect anaphylactic hypotension in conscious rats.

    PubMed

    Cui, Sen; Shibamoto, Toshishige; Zhang, Wei; Kurata, Yasutaka; Kashimura, Osamu; Miyamae, Shunichi

    2010-09-01

    1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in

  13. Using Giant African Pouched Rats ("Cricetomys Gambianus") to Detect Landmines

    ERIC Educational Resources Information Center

    Poling, Alan; Weetjens, Bart J.; Cox, Christophe; Beyene, Negussie W.; Sully, Andrew

    2010-01-01

    Within the past decade, giant pouched rats have been used successfully to detect landmines. This manuscript summarizes how these rats are trained and used operationally. The information provided is intended to be of practical value toward strengthening best practices in using "Cricetomys" for humanitarian purposes while simultaneously…

  14. A study of remote spatial memory in aged rats.

    PubMed

    Winocur, Gordon; Moscovitch, Morris; Rosenbaum, R Shayna; Sekeres, Melanie

    2010-01-01

    The effect of aging on remote spatial memory was tested in a group of 2-year-old rats (VR-O) that, as young adults, were reared for 3 months in a complex 'village' environment. The VR-O rats exhibited significant savings in finding the locations of specific reward compartments within the village, relative to a group of old rats (VNR-O) experiencing the village for the first time. The VNR-O rats were also impaired, relative to naive young rats, in learning the reward locations. Probe tests indicated that the VR-O rats retained allocentric spatial memory for the environment and were not using sensory or other non-spatial cues to guide behaviour. Overall, the results indicate that the aged rats experienced a decline in the ability to learn and remember detailed spatial relationships and that the VR-O group's successful performance on the remote spatial memory test was guided by a form of schematic memory that captured the essential features of the village environment. The potential contribution of the hippocampus to the pattern of lost and spared learning and memory observed in the aged rats was discussed.

  15. Raloxifene effects on thyroid gland morphology in ovariectomized rats.

    PubMed

    de Araujo, Luiz Felipe Bittencourt; Grozovsky, Renata; de Campos Pinheiro, Mônica; de Carvalho, Jorge José; Vaisman, Mário; Carvalho, Denise P

    2008-10-01

    We aimed to analyze the effects of raloxifene and estrogen on thyroid gland morphology of ovariectomized rats. Raloxifene treatment led to effects similar to those of estrogen on thyroid glands from ovariectomized rats, so that both were able to normalize the changes detected after ovariectomy.

  16. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  17. Inhalation toxicity of methyl difluoromalonyl fluoride in rats

    SciTech Connect

    Kennedy, G.L. Jr.; Burgess, B.A.; Chen, H.C.

    1988-06-01

    Methyl 2,2-difluoromalonyl fluoride (MMF) is highly toxic by inhalation producing mortality in rats exposed for 4 hours to 0.55 mg/L. Repeated inhalation exposures of rats to 0.009 mg/L produced irritation but no other signs of a toxic response. Mortality was encountered following repeated exposures to 0.066 mg/L.

  18. Cardiac and thermal homeostasis in the aging Brown Norway rat.

    EPA Science Inventory

    The Brown Norway (BN) rat is a popular strain for aging studies. There is little information on effects of age on baseline cardiac and thermoregulatory parameters in undisturbed BN rats even though cardiac and thermal homeostasis is linked to many pathological deficits in the age...

  19. Sympathetic neuroaxonal dystrophy in the aged rat pineal gland.

    PubMed

    Schmidt, Robert E; Dorsey, Denise A; Parvin, Curtis A; Beaudet, Lucie N

    2006-10-01

    Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats showed loss of nerve terminals as well as the development of neuroaxonal dystrophy (NAD), an ultrastructurally distinctive distal axonopathy, far in excess of that in young control rats. Immunolocalization of tyrosine hydroxylase confirmed the age-related loss of normal noradrenergic innervation and development of NAD. NAD was more frequent in aged female rats compared to males and was particularly severe in aged female Sprague-Dawley rats compared to Fischer-344 rats. Pineal NGF content was significantly increased or unchanged in female and male aged Fischer-344 rats, respectively, compared to young controls. The rat pineal is a sensitive experimental model for the quantitative ultrastructural examination of age-related neuropathological changes in nerve terminals of postganglionic noradrenergic sympathetic axons, changes which may reflect similar changes in the diffusely distributed sympathetic innervation of other targeted endorgans.

  20. Effect of housing rats within a pyramid on stress parameters.

    PubMed

    Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2003-11-01

    The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.

  1. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    DTIC Science & Technology

    1984-10-01

    Clara cells and alveolar type II cells from control and beta- naphthoflavone-pretreated rats. Cancer Res. 42:4658-4663. Kaighn, M.E., (1973), Human ...alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine , dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

  2. Rats Depend on Habit Memory for Discrimination Learning and Retention

    ERIC Educational Resources Information Center

    Broadbent, Nicola J.; Squire, Larry R.; Clark, Robert E.

    2007-01-01

    We explored the circumstances in which rats engage either declarative memory (and the hippocampus) or habit memory (and the dorsal striatum). Rats with damage to the hippocampus or dorsal striatum were given three different two-choice discrimination tasks (odor, object, and pattern). These tasks differed in the number of trials required for…

  3. [The blastomogenic effect of 249Bk in rats].

    PubMed

    Moskalev, Iu I; Zalikin, G A; Zhorova, E S; Nisimov, P G

    1984-01-01

    It is shown that 249Bk nitrate injected intraperitoneally in a wide range of doses to albino mongrel female rats is preferentially accumulated in the bony tissue (39.8%) and liver (18.4%). Incorporation of 249Bk to rats results in development of osteosarcomas, neoplasms of hemopoietic and lymphoid tissues, mammary tumours, thyroid and pituitary glands.

  4. Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats.

    PubMed

    Makni, Mohamed; Sefi, Mediha; Fetoui, Hamadi; Garoui, El Mouldi; Gargouri, Nabil K; Boudawara, Tahia; Zeghal, Najiba

    2010-01-01

    This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications.

  5. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

  6. Intelligence-Augmented Rat Cyborgs in Maze Solving

    PubMed Central

    Yu, Yipeng; Pan, Gang; Gong, Yongyue; Xu, Kedi; Zheng, Nenggan; Hua, Weidong; Zheng, Xiaoxiang; Wu, Zhaohui

    2016-01-01

    Cyborg intelligence is an emerging kind of intelligence paradigm. It aims to deeply integrate machine intelligence with biological intelligence by connecting machines and living beings via neural interfaces, enhancing strength by combining the biological cognition capability with the machine computational capability. Cyborg intelligence is considered to be a new way to augment living beings with machine intelligence. In this paper, we build rat cyborgs to demonstrate how they can expedite the maze escape task with integration of machine intelligence. We compare the performance of maze solving by computer, by individual rats, and by computer-aided rats (i.e. rat cyborgs). They were asked to find their way from a constant entrance to a constant exit in fourteen diverse mazes. Performance of maze solving was measured by steps, coverage rates, and time spent. The experimental results with six rats and their intelligence-augmented rat cyborgs show that rat cyborgs have the best performance in escaping from mazes. These results provide a proof-of-principle demonstration for cyborg intelligence. In addition, our novel cyborg intelligent system (rat cyborg) has great potential in various applications, such as search and rescue in complex terrains. PMID:26859299

  7. Intelligence-Augmented Rat Cyborgs in Maze Solving.

    PubMed

    Yu, Yipeng; Pan, Gang; Gong, Yongyue; Xu, Kedi; Zheng, Nenggan; Hua, Weidong; Zheng, Xiaoxiang; Wu, Zhaohui

    2016-01-01

    Cyborg intelligence is an emerging kind of intelligence paradigm. It aims to deeply integrate machine intelligence with biological intelligence by connecting machines and living beings via neural interfaces, enhancing strength by combining the biological cognition capability with the machine computational capability. Cyborg intelligence is considered to be a new way to augment living beings with machine intelligence. In this paper, we build rat cyborgs to demonstrate how they can expedite the maze escape task with integration of machine intelligence. We compare the performance of maze solving by computer, by individual rats, and by computer-aided rats (i.e. rat cyborgs). They were asked to find their way from a constant entrance to a constant exit in fourteen diverse mazes. Performance of maze solving was measured by steps, coverage rates, and time spent. The experimental results with six rats and their intelligence-augmented rat cyborgs show that rat cyborgs have the best performance in escaping from mazes. These results provide a proof-of-principle demonstration for cyborg intelligence. In addition, our novel cyborg intelligent system (rat cyborg) has great potential in various applications, such as search and rescue in complex terrains.

  8. ATRAZINE EFFECTS ON EARLY PREGNANCY AND IMPLANATION IN THE RAT

    EPA Science Inventory

    Atrazine Effects on Early Pregnancy and Implantation in the Rat.
    A.M. Cummings, B.E. Rhodes*, and R.L. Cooper*.
    Reproductive Toxicology Division, NHEERL, USEPA, Research Triangle Park, NC
    Atrazine (ATR), an herbicide, can induce mammary tumors in rats. ATR can also sup...

  9. Corrupted colonic crypt fission in carcinogen-treated rats

    PubMed Central

    2017-01-01

    Background The colonic crypts in rats reproduce themselves by symmetric fission at the base of the crypts, and proceeding upwards, generate two separate identical crypts. Recently we reported corrupted colonic crypt fission (CCCF) in rats with colonic carcinoma. Here we investigated whether CCCF also occurred in the colonic mucosa without carcinoma in carcinogen-treated rats. Methods Filed Swiss-roll sections from 35 male rats (25 treated with 1,2-dimethyhydrazine (DMH) suspended in EDTA solution, and 10 EDTA-treated) were reviewed. CCCF were regarded those with either asymmetric basal fission, asymmetric lateral sprouting/lateral fission, basal dilatations, or spatial aberrations of the normal (vertical) axis. Results 202 CCCF (38%) were recorded amongst 533 crypts with fission in DMH-treated rats, and only one CCCF (0.1%) was found amongst 571 crypts with fission in EDTA-treated rats (p<0.05). The basal aspect of four adenomas included in Swiss roll sections exhibited CCCF lined either with indigenous (non-dysplastic) epithelium or with dysplastic epithelium. Conclusion It was demonstrated that CCCF without dysplasia develop in carcinogen-treated SD rats. As judged by the figures presented, the possibility that the epithelium in those corrupted crypts was successively replaced by top-down growing dysplastic cells, could not be totally rejected. This is the first report showing that non-dysplastic CCCF may antedate the very early stages of colonic carcinogenesis in SD rats. PMID:28273142

  10. Angiotensin II-noradrenergic interactions in renovascular hypertensive rats.

    PubMed Central

    Zimmerman, J B; Robertson, D; Jackson, E K

    1987-01-01

    This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release. PMID:3301900

  11. Acute Oral Toxicity of Nitroguanidine in Male and Female Rats

    DTIC Science & Technology

    1988-03-01

    Baker HJ, Lindsey JR, Weisbroth SH, eds. Mycoplasmal and rickettsial diseases. In: The laboratory rat . Volume I. Biology and...were used for Limit Test animals. Pretest conditioning: Cuarantine/acclimation 10-24 Aug 84. Justification: The laboratory rat has proven to be

  12. Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat

    DTIC Science & Technology

    1997-07-01

    AD GRANT NUMBER DAMDI7-94-J-4040 TITLE: Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat PRINCIPAL INVESTIGATOR: Michael Gould, Ph.D...Carcinoma Suppressor Genes in the Laboratory Rat DAMDI7-94-J-4040 6. AUTHOR(S) Michael Gould, Ph.D. Hong Lan, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND

  13. Delay Discounting of Qualitatively Different Reinforcers in Rats

    ERIC Educational Resources Information Center

    Calvert, Amanda L.; Green, Leonard; Myerson, Joel

    2010-01-01

    Humans discount larger delayed rewards less steeply than smaller rewards, whereas no such magnitude effect has been observed in rats (and pigeons). It remains possible that rats' discounting is sensitive to differences in the quality of the delayed reinforcer even though it is not sensitive to amount. To evaluate this possibility, Experiment 1…

  14. The Effects of Reinforcer Magnitude on Timing in Rats

    ERIC Educational Resources Information Center

    Ludvig, Elliot A.; Conover, Kent; Shizgal, Peter

    2007-01-01

    The relation between reinforcer magnitude and timing behavior was studied using a peak procedure. Four rats received multiple consecutive sessions with both low and high levels of brain stimulation reward (BSR). Rats paused longer and had later start times during sessions when their responses were reinforced with low-magnitude BSR. When estimated…

  15. The Diabetic Nephropathy and the Development of Hypertension in Rats

    PubMed Central

    Zuccollo, Adriana; Navarro, Monica

    2001-01-01

    The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group, of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes. PMID:12369707

  16. Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

    PubMed

    Rui, Yongjun; Pan, Feng; Mi, Jingyi

    2016-10-01

    The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc.

  17. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  18. Wavelet-based analysis of blood pressure dynamics in rats

    NASA Astrophysics Data System (ADS)

    Pavlov, A. N.; Anisimov, A. A.; Semyachkina-Glushkovskaya, O. V.; Berdnikova, V. A.; Kuznecova, A. S.; Matasova, E. G.

    2009-02-01

    Using a wavelet-based approach, we study stress-induced reactions in the blood pressure dynamics in rats. Further, we consider how the level of the nitric oxide (NO) influences the heart rate variability. Clear distinctions for male and female rats are reported.

  19. Biochemical and histochemical adaptations of skeletal muscle to rat suspension

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.

    1984-01-01

    The influence of rat suspension on soleus disuse and atrophy was investigated to measure changes in fiber area and number and to determine if suspension elicited changes in lysosomal protease activity and rate of calcium uptake by the sarcoplasmic reticulum. The infuence of rat suspension on myosin light chain phosphorylation and succinate dehydrogenase activity are determined.

  20. Induction of tunica vaginalis mesotheliomas in rats by xenobiotics.

    PubMed

    Maronpot, R R; Zeiger, E; McConnell, E E; Kolenda-Roberts, H; Wall, H; Friedman, M A

    2009-01-01

    To better understand the relevance of tunica vaginalis mesotheliomas (TVM) to human cancer risk, we examined the nature of TVM responses in 21 published rat cancer bioassays against the backdrop of the biology and molecular biology of mesothelium, and of spontaneous and treatment-induced TVM. Although relatively rare in all species including humans, TVM are seen most frequently in F344 male rats, as opposed to other rat strains, and are causally associated with the high background incidence of Leydig-cell tumors of the testes of these rats. Hormone imbalance brought about by perturbations of the endocrine system is proposed as a key factor leading to both spontaneous and treatment-associated TVM. Of 21 F344 rat studies with a treatment-associated TVM response, 7 were judged to have a nonsignificant to marginal response, 11 had a robust TVM response, and 3 were noninformative due to early mortality from other induced tumors. Of the 11 chemicals with robust responses, 8 were directly mutagenic in Salmonella and 3 are known to be mutagenic after metabolism. Only 2 of the 7 with nonsignificant to marginal responses were Ames test positive. TVM induction is a male F344 rat-specific event, and chemicals/agents that induce only TVM in the male F344 rat from a typical two-sex rat and mouse chronic bioassay are likely irrelevant in human risk assessment.

  1. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    PubMed

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines.

  2. Fix and Sample with Rats in the Dynamics of Choice

    ERIC Educational Resources Information Center

    Aparicio, Carlos F.; Baum, William M.

    2006-01-01

    The generality of the molar view of behavior was extended to the study of choice with rats, showing the usefulness of studying order at various levels of extendedness. Rats' presses on two levers produced food according to concurrent variable-interval variable-interval schedules. Seven different reinforcer ratios were arranged within each session,…

  3. Repeated administration of adenosine increases its cardiovascular effects in rats.

    PubMed

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  4. Impact of predatory threat on fear extinction in Lewis rats.

    PubMed

    Goswami, Sonal; Cascardi, Michele; Rodríguez-Sierra, Olga E; Duvarci, Sevil; Paré, Denis

    2010-10-01

    Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.

  5. THE ETIOLOGY OF RAT-BITE FEVER

    PubMed Central

    Blake, Francis G.

    1916-01-01

    The similarity in the cases of rat-bite fever recorded in the literature establishes it as a definite clinical entity. The same symptomatology occurs in cases from Asia, Europe, and America. The greater frequency of the disease in Japan than elsewhere is probably due to the housing conditions and habits of the people resulting in the more frequent occurrence of rat-bites. It does not seem necessary to consider that cases occurring in Europe and America are due to the bites of rats that have been imported from Japan. The clinical picture and course of the disease indicate that it is infectious in origin. Until Schottmüller's case appeared in 1914, the etiology had been undiscovered. He isolated from his case in eight consecutive blood cultures a streptothrix which he has designated Streptothrix muris ratti. His work has been confirmed by the isolation of an identical streptothrix from the blood during life and at autopsy in the case here reported. Further confirmation of the etiological relationship of this organism to the infection in our patient is found in the production of powerful agglutinins for the organism in the blood serum of this case and in the demonstration of the organism in the vegetation on the mitral valve. It is not unreasonable to suppose that Proescher (13) observed the same organism in the sections of the excised wound in his case. Although it is fully realized that Koch's postulates have not been fulfilled in the absence of successful animal experimentation, nevertheless the accumulated evidence here presented leaves little reason to doubt that the specific cause of rat-bite fever is Streptothrix muris ratti. The pathology of rat-bite fever has hitherto been largely a matter of surmise. One autopsy only has been recorded in the literature (Miura (22)), and nothing abnormal was noted other than injection of the pial vessels. The autopsy in the case here reported has proved of considerable interest in the extent and character of the lesions

  6. Integration of the Rat Recombination and EST Maps in the Rat Genomic Sequence and Comparative Mapping Analysis With the Mouse Genome

    PubMed Central

    Wilder, Steven P.; Bihoreau, Marie-Thérèse; Argoud, Karène; Watanabe, Takeshi K.; Lathrop, Mark; Gauguier, Dominique

    2004-01-01

    Inbred strains of the laboratory rat are widely used for identifying genetic regions involved in the control of complex quantitative phenotypes of biomedical importance. The draft genomic sequence of the rat now provides essential information for annotating rat quantitative trait locus (QTL) maps. Following the survey of unique rat microsatellite (11,585 including 1648 new markers) and EST (10,067) markers currently available, we have incorporated a selection of 7952 rat EST sequences in an improved version of the integrated linkage-radiation hybrid map of the rat containing 2058 microsatellite markers which provided over 10,000 potential anchor points between rat QTL and the genomic sequence of the rat. A total of 996 genetic positions were resolved (avg. spacing 1.77 cM) in a single large intercross and anchored in the rat genomic sequence (avg. spacing 1.62 Mb). Comparative genome maps between rat and mouse were constructed by successful computational alignment of 6108 mapped rat ESTs in the mouse genome. The integration of rat linkage maps in the draft genomic sequence of the rat and that of other species represents an essential step for translating rat QTL intervals into human chromosomal targets. PMID:15060020

  7. Response to novelty in the laboratory Wistar rat, wild-captive WWCPS rat, and the gray short-tailed opossum (Monodelphis domestica).

    PubMed

    Pisula, Wojciech; Turlejski, Krzysztof; Stryjek, Rafał; Nałęcz-Tolak, Aleksandra; Grabiec, Marta; Djavadian, Rouzanna L

    2012-10-01

    Behavior of the laboratory gray short-tailed opossums (Monodelphis domestica), Warsaw Wild Captive Pisula Stryjek rats (WWCPS) and laboratory rats (Wistar) has been registered in the period of familiarization with a new environment and consecutive confrontation with a novel, innocuous object placed in that familiarized environment. In the new environment the sequence of anxiety, investigation, and habituation was shortest in the opossum, longer in the laboratory rat and longest in the WWCPS rat. When placed in it, gray short-tailed opossums investigated the new environment with the shortest delay and most intensity. In reaction to novel objects, opossums and laboratory rats prolonged the time spent in the proximity of the new object, while the WWCPS rat did not show that reaction. Both opossums and laboratory rats increased the number of contacts with the new object, whereas WWCPS rats reduced those contacts. Behavior of all three species and lines grouped in different clusters. Some other quantitative and qualitative differences in behavior of the investigated animals are also described, showing a higher level of anxiety in both lines of rats than in the opossum. Behavioral differences between species and lines of animals used in this study may be attributed to different ecological adaptations of rats and opossums and to the effect of domestication in the laboratory rats. These behavioral differences make comparisons of opossums vs rat, and wild rat vs laboratory rat interesting models for studying the brain mechanisms of anxiety and neotic motivations.

  8. Rat Genome Database: a unique resource for rat, human, and mouse quantitative trait locus data.

    PubMed

    Nigam, Rajni; Laulederkind, Stanley J F; Hayman, G Thomas; Smith, Jennifer R; Wang, Shur-Jen; Lowry, Timothy F; Petri, Victoria; De Pons, Jeff; Tutaj, Marek; Liu, Weisong; Jayaraman, Pushkala; Munzenmaier, Diane H; Worthey, Elizabeth A; Dwinell, Melinda R; Shimoyama, Mary; Jacob, Howard J

    2013-09-16

    The rat has been widely used as a disease model in a laboratory setting, resulting in an abundance of genetic and phenotype data from a wide variety of studies. These data can be found at the Rat Genome Database (RGD, http://rgd.mcw.edu/), which provides a platform for researchers interested in linking genomic variations to phenotypes. Quantitative trait loci (QTLs) form one of the earliest and core datasets, allowing researchers to identify loci harboring genes associated with disease. These QTLs are not only important for those using the rat to identify genes and regions associated with disease, but also for cross-organism analyses of syntenic regions on the mouse and the human genomes to identify potential regions for study in these organisms. Currently, RGD has data on >1,900 rat QTLs that include details about the methods and animals used to determine the respective QTL along with the genomic positions and markers that define the region. RGD also curates human QTLs (>1,900) and houses>4,000 mouse QTLs (imported from Mouse Genome Informatics). Multiple ontologies are used to standardize traits, phenotypes, diseases, and experimental methods to facilitate queries, analyses, and cross-organism comparisons. QTLs are visualized in tools such as GBrowse and GViewer, with additional tools for analysis of gene sets within QTL regions. The QTL data at RGD provide valuable information for the study of mapped phenotypes and identification of candidate genes for disease associations.

  9. Real-time application of the Rat Grimace Scale as a welfare refinement in laboratory rats

    PubMed Central

    Leung, Vivian; Zhang, Emily; Pang, Daniel SJ

    2016-01-01

    Rodent grimace scales have been recently validated for pain assessment, allowing evaluation of facial expressions associated with pain. The standard scoring method is retrospective, limiting its application beyond pain research. This study aimed to assess if real-time application of the Rat Grimace Scale (RGS) could reliably and accurately assess pain in rats when compared to the standard method. Thirty-two male and female Sprague-Dawley rats were block randomized into three treatment groups: buprenorphine (0.03 mg/kg, subcutaneously), multimodal analgesia (buprenorphine [0.03 mg/kg] and meloxicam [2 mg/kg], subcutaneously), or saline, followed by intra-plantar carrageenan. Real-time observations (interval and point) were compared to the standard RGS method using concurrent video-recordings. Real-time interval observations reflected the results from the standard RGS method by successfully discriminating between analgesia and saline treatments. Real-time point observations showed poor discrimination between treatments. Real-time observations showed minimal bias (<0.1) and acceptable limits of agreement. These results indicate that applying the RGS in real-time through an interval scoring method is feasible and effective, allowing refinement of laboratory rat welfare through rapid identification of pain and early intervention. PMID:27530823

  10. Calcium balance in mature male rats with unloaded hindlimbs

    NASA Technical Reports Server (NTRS)

    Navidi, Meena; Evans, Juliann; Wolinsky, Ira; Arnaud, Sara B.

    2004-01-01

    BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

  11. Neurotoxic behavioral effects of Lake Ontario salmon diets in rats

    SciTech Connect

    Hertzler, D.R. )

    1990-03-01

    Six experiments were conducted to examine possible neurotoxic effects of the exposure to contaminants in Lake Ontario salmon administered through the diets of rats. Rats were fed different concentrations of fish (8%, 15% or 30%) in one of three diet conditions: Lake Ontario salmon, Pacific Ocean salmon, or laboratory rat chow only. Following 20 days on the diets, rats were tested for five minutes per day in a modified open field for one or three days. Lake Ontario salmon diets consistently produced significantly lower activity, rearing, and nosepoke behaviors in comparison with ocean salmon or rat chow diet conditions. A dose-response effect for concentration of lake salmon was obtained, and the attenuation effect occurred in males, females, adult or young animals, and postweaning females, with fish sampled over a five-year period. While only two of several potential contaminants were tested, both fish and brain analyses of mirex and PCBs relate to the behavioral effects.

  12. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    PubMed Central

    Huang, He; Shan, Jiang; Pan, Xiao-hong; Wang, Hui-ping; Qian, Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats. PMID:16909474

  13. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    PubMed Central

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  14. Hyperuricemia induced by the uricosuric drug probenecid in rats.

    PubMed

    Shinosaki, T; Yonetani, Y

    1991-04-01

    Stimulation of uric acid production by the well-known uricosuric drug probenecid was studied using potassium oxonate-treated rats and eviscerated rats subjected to functional hepatectomy. In oxonate-treated rats, probenecid was hyperuricosuric, increasing the glomerular-filtered amounts of uric acid and causing marked hyperuricemia. This could be completely blocked by combination dosing with allopurinol, an inhibitor of xanthine oxidase. In eviscerated rats subjected to functional hepatectomy, probenecid also increased plasma uric acid and urinary uric acid excretion, but when given together with allopurinol, the increase of plasma uric acid was abolished with a remarkable increase of plasma hypoxanthine and xanthine. When probenecid was given by combination dosing with propranolol, a beta adrenoceptor antagonist, the hyperuricemia was also completely blocked. Thus, probenecid is concluded to stimulate uric acid production, probably via some interaction with endogenous catecholamine, resulting in hyperuricemia in rats, although it is a practical hypouricemic drug in humans.

  15. Effects of inactive parapoxvirus ovis on cytokine levels in rats

    PubMed Central

    AVCI, Oguzhan; BULUT, Oya; DIK, Irmak

    2015-01-01

    The aim of this study is to determine the effects of iPPOV on pro-inflammatory and anti-inflammatory cytokine levels in rats. iPPOV (1 ml/rat) was administered intraperitoneal route to 49 rats, except for 7 rats (Control, 0 group). Serum samples were collected from 7 rats at 1st, 2nd, 4th, 8th, 12th, 16th and 24th hr after treatments. Levels of TNF-α, IL-6, IL-12 and IL-10 were determined using ELISA. Administration of iPPOV stimulated TNF-α (16th and 24th hr) and IL-6 (12th, 16th and 24th hr) synthesis and caused fluctuations in IL-10 and IL-12 concentrations. In conclusion, increased cytokine levels could be attributed to immunomodulatory activity of iPPOV, however, detailed studies are required to fully understand effects of iPPOV on immune system. PMID:26290129

  16. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

    PubMed Central

    Chen, Qing-Ying; Wang, Guo-Guang; Li, Wei; Jiang, Yu-Xin; Lu, Xiao-Hua; Zhou, Ping-Ping

    2016-01-01

    Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats. PMID:26798657

  17. Gene Targeting in the Rat: Advances and Opportunities

    PubMed Central

    Jacob, Howard J.; Lazar, Jozef; Dwinell, Melinda R.; Moreno, Carol; Geurts, Aron M.

    2010-01-01

    The rat has long been a model favored by physiologists, pharmacologists, and neuroscientists. However, over the last two decades, many investigators in these fields have turned to the mouse because of its gene modification technologies and extensive genomic resources. While the genomic resources of the rat have nearly caught-up, gene targeting has lagged far behind, limiting the value of the rat for many investigators. In the last two years, advances in transposon- and zinc finger nuclease-mediated gene knockout as well as the establishment and culturing of embryonic and inducible pluripotent stem cells have created new opportunities for rat genetic research. Here, we provide a high-level description and potential uses of these new technologies for investigators using the rat for biomedical research. PMID:20869786

  18. EXACERBATED MECHANICAL ALLODYNIA IN RATS WITH DEPRESSION-LIKE BEHAVIOR

    PubMed Central

    Zeng, Qing; Wang, Shuxing; Lim, Grewo; Yang, Liling; Mao, Ji; Sung, Backil; Chang, Yang; Lim, Jeong-Ae; Guo, Gongshe; Mao, Jianren

    2008-01-01

    Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report that both mechanical allodynia and depression-like behavior were significantly exacerbated after peripheral nerve injury in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats with demonstrable depression-like behavior. Administration of melatonin into the anterior cingular cortex contralateral to peripheral nerve injury prevented the exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in WKY rats. Moreover, there was a lower plasma melatonin concentration and a lower melatonin receptor expression in the anterior cingular cortex in WKY rats than in Wistar rats. These results suggest that there exists a reciprocal relationship between mechanical allodynia and depression-like behavior and the melotoninergic system in the anterior cingular cortex might play an important role in the interaction between pain and depression. PMID:18289511

  19. Effect of ETBE on reproductive steroids in male rats and rat Leydig cell cultures.

    PubMed

    de Peyster, Ann; Stanard, Bradley; Westover, Christian

    2009-10-08

    These experiments were conducted to follow up on a report of testis seminiferous tubular degeneration in Fischer 344 rats treated with high doses of ethyl t-butyl ether (ETBE). Also, high doses of a related compound, methyl t-butyl ether (MTBE), had been shown to reduce circulating testosterone (T) in rats. Isolated rat Leydig cells were used to compare hCG-stimulated T production following exposure to ETBE, MTBE, and their common main metabolite, TBA. In addition, male Fischer 344 rats were gavaged daily with 600 mg/kg, 1200 mg/kg or 1800 mg/kg ETBE in corn oil (n=12) for 14 days, the 1200 mg/kg dose chosen for comparison with a prior 14-day MTBE gavage experiment. In cell culture experiments, TBA was more potent than either ETBE or MTBE, both of which caused similar inhibition of T production at equimolar concentrations. In the in vivo study, no significant plasma T reduction was seen 1h after the final 1200 mg/kg ETBE dose, whereas 1200 mg/kg MTBE had significantly lowered T when administered similarly to Sprague-Dawley rats. Some rats treated with 1800 mg/kg ETBE had noticeably lower T levels, and the group average T level was 66% of corn oil vehicle control (p>0.05) with high variability also evident in ETBE-treated rats. 17beta-Estradiol had been increased by 1200 mg/kg MTBE, and was elevated in the 1200 and 1800 mg/kg ETBE dose groups (p<0.05), both groups also experiencing significantly reduced body weight gain. None of these effects were seen with 600 mg/kg/day ETBE. No definitive evidence of androgen insufficiency was seen in accessory organ weights, and no testicular pathology was observed after 14 days in a small subset of 1800 mg/kg ETBE-treated animals. Like MTBE, ETBE appears to be capable of altering reproductive steroid levels in peripheral blood sampled 1h after treatment, but only with extremely high doses that inhibit body weight gain and may produce mortality.

  20. Comparison of starvation and elastase models of emphysema in the rat

    SciTech Connect

    Harkema, J.R.; Mauderly, J.L.; Gregory, R.E.; Pickrell, J.A.

    1984-01-01

    Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease. 44 references, 5 figures, 4 tables.

  1. Inflammation compromises renal dopamine D1 receptor function in rats

    PubMed Central

    Chugh, Gaurav; Lokhandwala, Mustafa F.

    2009-01-01

    We tested the effects of inflammation on renal dopamine D1 receptor signaling cascade, a key pathway that maintains sodium homeostasis and blood pressure during increased salt intake. Inflammation was produced by administering lipopolysaccharide (LPS; 4 mg/kg ip) to rats provided without (normal salt) and with 1% NaCl in drinking water for 2 wk (high salt). Control rats had saline injection and received tap water. We found that LPS increased the levels of inflammatory cytokines, interleukin-6, and tumor necrosis factor-α in the rats given either normal- or high-salt intake. Also, these rats had higher levels of oxidative stress markers, malondialdehyde and nitrotyrosine, and lower levels of antioxidant enzyme superoxide dismutase in the renal proximal tubules (RPTs). The nuclear levels of transcription factors NF-κB increased and Nrf2 decreased in the RPTs in response to LPS in rats given normal and high salt. Furthermore, D1 receptor numbers, D1 receptor proteins, and D1 receptor agonist (SKF38393)-mediated 35S-GTPγS binding decreased in the RPTs in these rats. The basal activities of Na-K-ATPase in the RPTs were similar in control and LPS-treated rats given normal and high salt. SKF38393 caused inhibition of Na-K-ATPase activity in the primary cultures of RPTs treated with vehicle but not in the cultures treated with LPS. Furthermore, LPS caused an increase in blood pressure in the rats given high salt but not in the rats given normal salt. These results suggest that LPS differentially regulates NF-κB and Nrf2, produces inflammation, decreases antioxidant enzyme, increases oxidative stress, and causes D1 receptor dysfunction in the RPTs. The LPS-induced dysfunction of renal D1 receptors alters salt handling and causes hypertension in rats during salt overload. PMID:19794106

  2. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  3. Lemon juice has protective activity in a rat urolithiasis model

    PubMed Central

    Touhami, Mohammed; Laroubi, Amine; Elhabazi, Khadija; Loubna, Farouk; Zrara, Ibtissam; Eljahiri, Younes; Oussama, Abdelkhalek; Grases, Félix; Chait, Abderrahman

    2007-01-01

    Background The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. Methods The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 μl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Results Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. Conclusion These data suggest that lemon juice has a protective activity against urolithiasis. PMID:17919315

  4. The effects of exposure to electromagnetic field on rat myocardium.

    PubMed

    Kiray, Amac; Tayefi, Hamid; Kiray, Muge; Bagriyanik, Husnu Alper; Pekcetin, Cetin; Ergur, Bekir Ugur; Ozogul, Candan

    2013-06-01

    Exposure to electromagnetic fields (EMFs) causes increased adverse effects on biological systems. The aim of this study was to investigate the effects of EMF on heart tissue by biochemical and histomorphological evaluations in EMF-exposed adult rats. In this study, 28 male Wistar rats weighing 200-250 g were used. The rats were divided into two groups: sham group (n = 14) and EMF group (n = 14). Rats in sham group were exposed to same conditions as the EMF group except the exposure to EMF. Rats in EMF group were exposed to a 50-Hz EMF of 3 mT for 4 h/day and 7 days/week for 2 months. After 2 months of exposure, rats were killed; the hearts were excised and evaluated. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 immunohistochemistry were performed. In EMF-exposed group, levels of lipid peroxidation significantly increased and activities of superoxide dismutase and glutathione peroxidase decreased compared with sham group. The number of TUNEL-positive cells and caspase-3 immunoreactivity increased in EMF-exposed rats compared with sham. Under electron microscopy, there were mitochondrial degeneration, reduction in myofibrils, dilated sarcoplasmic reticulum and perinuclear vacuolization in EMF-exposed rats. In conclusion, the results show that the exposure to EMF causes oxidative stress, apoptosis and morphologic damage in myocardium of adult rats. The results of our study indicate that EMF-related changes in rat myocardium could be the result of increased oxidative stress. Further studies are needed to demonstrate whether the exposure to EMF can induce adverse effects on myocardium.

  5. Seizures and reproductive function: insights from female rats with epilepsy

    PubMed Central

    Scharfman, Helen E.; Kim, Michelle; Hintz, Tana M.; MacLusky, Neil J.

    2009-01-01

    OBJECTIVE Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment. METHODS Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed “epileptic.” Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary. PMID:19107990

  6. A new strain of rat for functional analysis of PINA.

    PubMed

    Ahmed, Samreen; Deng, Jie; Borjigin, Jimo

    2005-06-13

    Long Evans cinnamon (LEC) rat is an animal model for human Wilson disease (WD) due to a deletion in Atp7b, the copper transporter defective in WD patients. Previously, we have demonstrated presence of an alternative product termed PIneal Night-specific ATPase (PINA) generated by an intronic promoter in Atp7b gene. Analysis of LEC rat in this study demonstrates that PINA is absent in the LEC pineal establishing its usefulness for investigating PINA function. Studies of the LEC pineal, however, revealed an additional defect in serotonin N-acetyltransferase (NAT), the key enzyme in melatonin production. Linkage studies confirm that the NAT phenotype is entirely independent of PINA mutation in the pineal gland of LEC rats, and sequence analysis demonstrates that NAT defect is due to a point mutation in NAT coding region. In addition, we demonstrate that the cinnamon coat color of the LEC rat is unlinked to PINA and NAT deficiencies in these animals. To facilitate further functional analysis of PINA in pineal physiology, we crossed LEC rats with PVG rats that are wildtype for PINA, NAT and coat color, and obtained rats that are defective only in PINA/Atp7b locus (termed LPP rats) and normal for NAT activity and coat color. Furthermore, we have identified the deletion breakpoint of Atp7b gene in LPP rats, which allows simplified genotyping of mutant animals. The separation of PINA mutation from both NAT and coat color mutations in the new LPP rats will permit better functional studies of PINA in pineal circadian physiology.

  7. Individual differences in oral nicotine intake in rats.

    PubMed

    Nesil, Tanseli; Kanit, Lutfiye; Collins, Allan C; Pogun, Sakire

    2011-01-01

    To study individual differences in nicotine preference and intake, male and female rats were given free access to a choice of oral nicotine (10 or 20 mg/L) or water for 24 h/day for periods of at least six weeks, starting at adolescence or adulthood. A total of 341 rats, were used in four different experiments; weight, nicotine intake and total liquid consumption were recorded weekly. Results show that rats can discriminate nicotine from water, can regulate their intake, and that there are readily detected individual differences in nicotine preference. Ward analyses indicated that the animals could be divided into minimum, median and maximum preferring subgroups in all experiments. The effect of saccharine on nicotine intake was also evaluated; although the addition of saccharine increased total intake, rats drank unsweetened nicotine solutions and those with higher preferences for nicotine, preferred nicotine over water with or without saccharine added. Nicotine reduced weight gain and the effect was more pronounced in females than males. The average nicotine consumption of adolescent rats was higher than adults and nicotine exposure during adolescence reduced nicotine intake in adult rats. About half of the rats which had access to nicotine as adolescents and also as adults had a persistent pattern of consumption; the behavior was very stable in the female minimum preferring groups and a much higher ratio of rats sustained their adolescent behavior as adults. The change in preference was more pronounced when there was an interval between adolescent and adult exposure; female rats showed a more stable behavior than males suggesting a greater role for environmental influences on males. In conclusion, marked individual differences were observed in oral nicotine intake as measured in a continuous access 2-bottle choice test. Age and sex of the subjects and previous exposure to nicotine are significant factors which affect preference in rats.

  8. Repeated social defeat stress induces chronic hyperthermia in rats.

    PubMed

    Hayashida, Sota; Oka, Takakazu; Mera, Takashi; Tsuji, Sadatoshi

    2010-08-04

    Psychological stressors are known to increase core body temperature (T(c)) in laboratory animals. Such single stress-induced hyperthermic responses are typically monophasic, as T(c) returns to baseline within several hours. However, studies on the effects of repeated psychological stress on T(c) are limited. Therefore, we measured T(c) changes in male Wistar rats after they were subjected to 4 social defeat periods (each period consisting of 7 daily 1h stress exposures during the light cycle followed by a stress-free day). We also assessed affective-like behavioral changes by elevated plus maze and forced swim tests. In the stressed rats, the first social defeat experience induced a robust increase in T(c) (+1.3 degrees C). However, the T(c) of these rats was not different from control animals during the subsequent dark period. In comparison, after 4 periods of social defeat, stressed rats showed a small but significantly higher (+0.2-0.3 degree C) T(c) versus control rats during both light and dark periods. Stressed rats did not show increased anxiety-like behavior versus control rats as assessed by the elevated plus maze test. However, in the forced swim test, the immobility time of stressed rats was significantly longer versus control rats, suggesting an increase in depression-like behavior. Furthermore, hyperthermia and depression-like behavior were still observed 8 days after cessation of the final social defeat session. These results suggest that repeated social defeat stress induces a chronic hyperthermia in rats that is associated with behavior resembling depression but not anxiety.

  9. Caloric restriction increases internal iliac artery and penil nitric oxide synthase expression in rat: comparison of aged and adult rats.

    PubMed

    Ozbek, Emin; Simsek, Abdulmuttalip; Ozbek, Mustafa; Somay, Adnan

    2013-09-26

    Because of the positive corelation between healthy cardiovascular system and sexual life we aimed to evaluate the effect of caloric restriction (CR) on endothelial and neuronal nitric oxide synthase (eNOS, nNOS) expression in cavernousal tissues and eNOS expression in the internal iliac artery in young and aged rats. Young (3 mo, n = 7) and aged (24 mo, n = 7) male Sprague-Dawley rats were subjected to 40% CR and were allowed free access to water for 3 months. Control rats (n = 14) fed ad libitum had free access to food and water at all times. On day 90, rats were sacrificed and internal iliac arteries and penis were removed and parafinized, eNOS and nNOS expression evaluated with immunohistochemistry. Results were evaluated semiquantitatively. eNOS and nNOS expression in cavernousal tis- sue in CR rats were more strong than in control group in both young and old rats. eNOS expression was also higher in the internal iliac arteries of CR rats than in control in young and old rats. As a result of our study we can say that there is a positive link between CR and neurotransmitter of erection in cavernousal tissues and internal iliac arteries. CR has beneficial effect to prevent sexual dysfunction in young and old animals and possible humans.

  10. Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

    PubMed Central

    van der Geld, Ymke M; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G; Limburg, Pieter C; Kallenberg, Cees G M

    2007-01-01

    Aim In this study, we employed chimeric human/mouse Proteinase 3 (PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method Rats and mice were immunised with recombinant human PR3 (HPR3), recombinant murine PR3 (mPR3), single chimeric human/mouse PR3 (HHm, HmH, mHH, mmH, mHm, Hmm) or pools of chimeric proteins. Antibodies to mPR3 and HPR3 were measured by ELISA. Antibodies to rat PR3 were determined by indirect immunofluorescence (IIF) on rat white blood cells. Urinalysis was performed by dipstick analysis. Kidney and lung tissue was obtained for pathological examination. Results In mice, immunisation with the chimeric human/mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunised with the chimeric human/mouse PR3 Hmm, HmH and mmH, or a pool of the chimeric human/mouse PR3 proteins, produced antibodies selectively binding to rat granulocytes as detected by IIF. No gross pathological abnormalities could be detected in kidney or lungs of mice or rats immunised with chimeric human/mouse PR3. Conclusion Immunisation with chimeric human/mouse proteins induces autoantibodies to PR3 in rats and mice. Chimeric proteins can be instrumental in developing experimental models for autoimmune diseases. PMID:17644551