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  1. Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures

    Science.gov (United States)

    Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.

    1983-07-01

    Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.

  2. Features of electroretinogram on rat under different color stimulation

    Directory of Open Access Journals (Sweden)

    Qing-Lin Cao

    2014-04-01

    Full Text Available AIM: To research the feature of normal SD rat and retinal cone dysfunction(RCDrat electroretinogram(ERGunder different color stimulation and to explore its possible diagnostic value. METHODS: Six male SD rats and six RCD rats were used, all of which were mature rats. They were stimulated by red, white, blue and green light and the ERG was recorded. The wavelength of red, green and blue light were 625nm, 525nm and 470nm respectively and the white light was mixed by three color light.RESULTS: The response of ERG in normal SD rat under green and blue light stimulation were stronger than under red and white stimulation. The dark-adapted ERG of RCD rat responsed to color stimulation was similar to the ERG of normal SD rat, but the amplitude under each color stimulation was lower than that of normal SD rat. Light-adapted ERG response was hardly detected waveform.CONCLUSION: Rat is sensitive to blue and green light, which can be used as a suggested light stimulation in the ERG recording. The ERG of RCD rat is not specific for color stimulation, and at present we could not use color ERG as a diagnostic indicator.

  3. Trigeminovascular stimulation in conscious rats

    NARCIS (Netherlands)

    Kemper, RHA; Meijler, WJ; TerHorst, GJ

    1997-01-01

    INTRACISTERNAL infusion of capsaicin was used to induce intracranial trigeminovascular stimulation in conscious rats. Both behaviour and trigeminal nucleus caudalis c-fos expression were examined. Exploratory behaviour was dose-dependently reduced and different types of behaviours were induced with

  4. Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats.

    Science.gov (United States)

    Luna-Munguía, Hiram; Meneses, Alfredo; Peña-Ortega, Fernando; Gaona, Andres; Rocha, Luisa

    2012-01-01

    Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short-term, but not long-term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short-term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans.

  5. [Effect of prednisolon on trachea smooth muscle of normal rats and rats with fibrosing alveolitis].

    Science.gov (United States)

    Fedin, A N; Nekrasova, E A; Frolova, S A; Danilov, L N; Lebedeva, E S; Il'kovich, M M

    2007-01-01

    Effect of prednisolone on isolated preparations of trachea of normal rats and rats with fibrosing alveolitis was studied. Prednisolone at a concentration of 0.4 microg/l decreased responses of smooth muscle on stimulation of preganglionar nerve fibers at trachea areas with intramural ganglia in rats with acute alveolitis by 48%, while in normal rats--by 19% of control. In trachea preparations without ganglia, prednisolone at a dose of 10 microg/l decreased responses of muscle to the nerve fiber stimulation by 21.3%. The higher prednisolone doses were less efficient: 0.1-10 microg/l glucocorticoid practically did not affect the smooth muscle responses produced by stimulation of muscle cells. In rats with fibrosing alveolitis, 10 microg/l prednisolone restored the smooth muscle responses to control values in preparations of trachea with intramural ganglia. After the prednisolone treatment, amplitude of the rat trachea muscle contraction in response to the nerve fiber electric stimulation did not differ statistically significantly from control and 0.1-10 microg/l prednisolone did not change the response value. The conclusion is made that prednisolone affected the diseased rats more efficiently than the healthy animals. The character of the glucocorticoid effect depends on the presence of intramural ganglia in the trachea wall.

  6. Pharmacodynamic study on acute hypotensive activities of Carissa carandas extract in normal rats.

    Science.gov (United States)

    Shamim, Sumbul; Ahmad, Syed Iqbal

    2012-07-01

    This study aims to evaluate the effect of Carissa carandas extract on cardiovascular function of normal rats. Intravenous bolus injection of this extract in the doses of 5 mg kg(-1)_-45 mg kg(-1), produced dose dependent reduction in arterial blood pressure (p0.05). It was concluded that the Carissa carandas Ethanol extract possess potent acute hypotensive effect in normal rats. It stimulates the muscarinic receptors located on the endothelial cells of the vasculature. This stimulation results in the release of endothelial-derived relaxing factors (EDRFs) or nitric oxide that diffuses to vasculature smooth muscles and causes their relaxation.

  7. Calcium Activation Profile In Electrically Stimulated Intact Rat Heart Cells

    Science.gov (United States)

    Geerts, Hugo; Nuydens, Rony; Ver Donck, Luc; Nuyens, Roger; De Brabander, Marc; Borgers, Marcel

    1988-06-01

    Recent advances in fluorescent probe technology and image processing equipment have made available the measurement of calcium in living systems on a real-time basis. We present the use of the calcium indicator Fura-2 in intact normally stimulated rat heart cells for the spatial and dynamic measurement of the calcium excitation profile. After electric stimulation (1 Hz), the activation proceeds from the center of the myocyte toward the periphery. Within two frame times (80 ms), the whole cell is activated. The activation is slightly faster in the center of the cell than in the periphery. The mean recovery time is 200-400 ms. There is no difference along the cell's long axis. The effect of a beta-agonist and of a calcium antagonist is described.

  8. Effect of ischemia and cooling on the response to high frequency stimulation in rat tail nerves

    DEFF Research Database (Denmark)

    Andersen, Henning; Feldbæk Nielsen, Jørgen; Sørensen, Bodil

    2000-01-01

    In normal rat tail nerves the effect of temperature and ischemia on the response to long-term high frequency stimulation (HFS) (143 Hz) was studied. The effect of temperature was studied in two consecutive tests at 14 degrees C and 35 degrees C. Prior to the HFS the peak-to-peak amplitude (PP-amp...... ischemia to the rat tail, an additional fall of the PP-amp was seen after 15-20 min of HFS at both low (20 Hz) and high (143 Hz) stimulation frequencies. In conclusion, ischemia and cooling result in an impaired ability to transmit high frequency impulses.......In normal rat tail nerves the effect of temperature and ischemia on the response to long-term high frequency stimulation (HFS) (143 Hz) was studied. The effect of temperature was studied in two consecutive tests at 14 degrees C and 35 degrees C. Prior to the HFS the peak-to-peak amplitude (PP...

  9. Tegaserod (HTF 919) stimulates gut motility in normal horses.

    Science.gov (United States)

    Lippold, B S; Hildebrand, J; Straub, R

    2004-11-01

    It has been shown that the selective 5-HT4 receptor agonist tegaserod induces an increase in frequency and amplitude of contractions in isolated muscle preparations of equine ileum and pelvic flexure. To investigate the effects of tegaserod on gut motility and transit of spheres in normal horses. Six mature Freiberger horses were kept under standardised conditions. Effects of tegaserod (0.02 mg/kg bwt i.v. b.i.d. for 2 days) or vehicle on intestinal transit of barium-filled spheres, defaecation and gut sounds were studied in a cross-over design. Spheres were given via stomach tube prior to the first dosing of tegaserod or vehicle. Faeces were collected every 3 h and spheres eliminated were identified radiologically in the faeces. Tegaserod significantly accelerated the gastrointestinal (GI) transit time of spheres and increased the frequency of defaecation and scores of gut sounds compared to vehicle. The compound was well tolerated; no effects on behaviour, body temperature, heart rate, respiratory rate and clinical laboratory data were observed. Tegaserod efficaciously stimulated motility and accelerate GI transit in healthy horses. Tegaserod may offer therapeutic potential in horses suffering from impaction or paralytic ileus.

  10. [Thyroid stimulating immunoglobulin bioassay using cultured normal human thyroid cells].

    Science.gov (United States)

    Ando, M; Yamauchi, K; Tanaka, H; Mori, Y; Takatsuki, K; Yamamoto, M; Matsui, N; Tomita, A

    1985-08-20

    It is currently believed that the thyroid stimulating immunoglobulin (TSI) of Graves' disease is involved in the pathogenesis of hyperthyroidism through the stimulation of the adenylate cyclase-cyclic AMP system. To evaluate this mechanism, TSI in the serum of patients with Graves' disease was determined by its ability to generate cyclic AMP (cAMP) in monolayer cells prepared from a normal thyroid gland. The thyroid tissue was digested with collagenase, and the liberated follicles were collected from the supernatant and cultured for 7 days. One gram of thyroid tissue yielded more than 1 X 10(7) monolayer cells which were stored in aliquots at -80C. Cells (1 approximately 2 X 10(4)/0.28 cm2 microtiter well) were incubated for 4 hours in 0.2 ml Hanks solution poor in NaCl, with various amounts of bovine TSH (bTSH) or 1.5 mg/ml Graves' serum IgG extracted by polyethylene glycol. cAMP accumulated in medium and cells was measured by RIA. Total cAMP (both medium and cells) was about 4 times higher when NaCl was deleted from Hanks solution. Moreover, as more than 90% of the cAMP was released into the medium, it was possible to omit the measurement of cellular cAMP, which requires extraction. The increase in medium cAMP concentration was dependent upon the number of cells, incubation time, and dose of bTSH. Time course and dose response curves in medium cAMP stimulated by IgG from 3 Graves' patients paralleled those of bTSH equivalent units. Accordingly, TSI activity could be expressed in bTSH equivalent units (bTSH microUeq). The assay could detect 1.0 or 3.3 microU/ml of bTSH and was highly reproducible. TSI activity in all of 16 IgGs from normal subjects was under 3.3 bTSH microUeq/ml, while it was greater than 3.3 bTSH microUeq/ml in IgGs from 33 of 37 (89%) untreated patients with Graves disease. Of the 13 patients followed for 2 to 7 months while on antithyroid drugs, 12 had greater than 3.3 bTSH microUeq/ml and, with the exception of one, all showed a decrease in

  11. Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

    Science.gov (United States)

    Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

    1998-01-01

    The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

  12. Growth hormone does not stimulate early healing in rat tendons

    OpenAIRE

    2012-01-01

    Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twic...

  13. A microcontroller-based implantable nerve stimulator used for rats.

    Science.gov (United States)

    Sha, Hong; Zheng, Zheng; Wang, Yan; Ren, Chaoshi

    2005-01-01

    A microcontroller-based stimulator that can be flexible programmed after it has been implanted into a rat was studied. Programmability enables implanted stimulators to generate customized, complex protocols for experiments. After implantation, a coded light pulse train that contains information of specific identification will unlock a certain stimulator. If a command that changing the parameters is received, the microcontroller will update its flash memory after it affirms the commands. The whole size of it is only 1.6 cubic centimeters, and it can work for a month. The devices have been successfully used in animal behavior experiments, especially on rats.

  14. Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Eamruthai Wisetmuen

    2013-01-01

    Full Text Available Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ. Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively. Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively. Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF for control and HS-EE treated group, respectively and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively. Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion.

  15. Visceral and postural reflexes evoked by genital stimulation in urethane-anesthetized female rats.

    Science.gov (United States)

    Martinez-Gomez, M; Chirino, R; Beyer, C; Komisaruk, B R; Pacheco, P

    1992-03-20

    The present study describes several muscular reflexes produced by genital stimulation, the nerves that subserve them, and the visceral and postural effects induced by these reflexes. Electrical stimulation of the iliococcygeus (ic) and pubococcygeus (pc) (striated) muscles produced movement of the vaginal orifice and wall, membranous urethra, tail and pelvis. Electrical stimulation of the psoas major (pm) or iliacus (i) (striated) muscles produced movements of the lumbar vertebrae and extension of the ipsilateral hindlimb. Sensory mechanostimulation elicited responses of these muscles as follows: stimulation of the perineal skin, clitoral sheath or distal vagina produced reflex contraction of the ic and pc muscles. Stimulation of the cervix produced reflex contraction of the pm and i muscles and also blocked the above reflex contraction of the ic and pc muscles. Both the cervical stimulation-induced blockage of the ic and pc reflex response, and the cervical stimulation-induced activation of pm and i muscles was prevented by bilateral transection of the viscerocutaneous branch of the pelvic nerve. Based on the above observations, it is proposed that stimulation of the vaginal surface of the cervix resulting from penile intromission and/or seminal plug deposition during mating behavior in the rat may reflexively active pm and i, thereby contributing to the hindleg postural rigidity and lordotic dorsiflexion that are characteristic of the normal mating posture in female rats.

  16. Dihydroartemisinin-Stimulated Hyperplasia of Rat Lung Smooth Muscles

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    Utoh-Nedosa U. Anastasia

    2012-01-01

    Full Text Available Problem statement: Dihydroartemisinin was shown to produce two types of inhibitory effects on the cardiac muscles of rats. It was also shown to stimulate haemopoiesis in the lungs, liver, spleen, intestine and kidney of rats. This study attempted to find out the nature of the effect of oral dihydroartemisinin on the lungs of Wistar albino rats. Approach: The effects of dihydroartemisinin on the tissues of the lungs of wistar albino rats were investigated with five doses of Dihydroartemisinin (DHA administered for 5 days by oral intubation. The five tested doses were 1 mg kg-1, a repeated dose of 1, 2, 60 and 80 mg kg-1 DHA. Results: Histopathological examination of the tissue micrographs of the lungs of the dihydroartemisinin treated rats showed that in comparism with those of the controls, DHA had no adverse effects on the tissues of the lungs of the rats but rather produced a direct stimulatory effect on the smooth muscles of the lungs. This stimulation caused hyperplasia of these tissues which was observable histologically in tissue micrographs of the lungs. These effects of dihydroartemisinin on the tissues of the lungs of Wistar albino rats were dose, repetition and time dependent. Conclusion: These growth hormone-like stimulatory effects of dihydroartemisinin on the smooth muscles of the lungs suggest that DHA enhanced the functioning capacity of the lungs of the DHA-treated rats. These results suggest that dihydroartemisinin has possible respiration enhancement effects.

  17. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

    Science.gov (United States)

    Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

    2010-04-01

    The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

  18. Rewarding electrical brain stimulation in rats after peripheral nerve injury: decreased facilitation by commonly abused prescription opioids.

    Science.gov (United States)

    Ewan, Eric E; Martin, Thomas J

    2011-12-01

    Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the abuse liability of commonly abused prescription opioids. Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into the left ventral tegmental area (VTA). Rats were trained to lever press for intracranial electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl, hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second group of neuropathic rats were implanted with intrathecal catheters, and the effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of VTA ICSS were assessed. The effects of electrical stimulation of the VTA on mechanical allodynia were assessed in SNL rats. Responding for VTA ICSS was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a significant facilitation of VTA ICSS in control (maximum shift 24.10 ± 6.19 Hz) but not SNL rats (maximum shift 16.32 ± 7.49 Hz), but also reduced maximal response rates in SNL rats. Intrathecal administration of clonidine, adenosine, and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical stimulation of the VTA did not alter mechanical allodynia following nerve injury. The present data suggests that the positive reinforcing effects of commonly abused prescription opioids are diminished following nerve injury. In addition, alleviation of mechanical allodynia with nonopioid analgesics does not appear to stimulate limbic dopamine pathways originating from the VTA in SNL rats.

  19. Opening angles and residual strains in normal rat trachea

    Institute of Scientific and Technical Information of China (English)

    柳兆荣; 王忆勤; 滕忠照; 徐刚; 汤伟昌

    2002-01-01

    The no-load state and zero-stress state of the normal rat trachea were analyzed. It was found that there exist compressive residual strains in the inner wall region of the rat trachea and tensile residual strains in the outer wall region. The fact that the opening angle of the rat trachea cut at the cartilaginous region is significantly larger than that cut at the muscular portion shows that residual strains exist mainly in the muscular region in the rat trachea. It was also indicated that the opening angles and residual strains expressed by cutting at the muscular portion are basically identical along longitudinal location and those expressed by cutting in the cartilaginous region tend to increase in the longitudinal direction in the normal rat, and that there exists quantitatively positive correlation between the opening angles and residual strains in rat trachea. The results will help to further understand the opening angles and residual strains in the trachea and study tracheal remodeling in response to mechanical environment.

  20. Solcoseryl stimulates behavioural activity of rats.

    Science.gov (United States)

    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.

  1. Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    WU Sheng-tian; MA Yu; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Parkinson's disease(PD)is a common neurodegenerative disease,which occurs mainly in the elderly.Recent studies have demonstrated that apoptosis plays an important role in the occurrence and development of PD.Subthalamic nucleus deep brain stimulation(STN-DBS)has been recognized as an effective treatment for PD.Recent clinical observations have shown that STN-DBS was able to delay early PD progression,and experiments in animal models have also demonstrated a protective effect of STN-DBS on neurons.However,the correlation between the neuron-protective effect of STN-DBS and the progression of substantia nigra pars compacta(SNc)neuronal apoptosis is still unknown.The aim of this study was to investigate the protective effect and potential mechanism of STN-DBS on SNc neurons in PD rats.Methods After the establishment of a PD rat model by unilateral/2-point injection of 6-hydroxydopamine in the medial forebrain bundle of the brain,DBS by implanting electrodes in the STN was administered.Behavioral changes were observed,and morphological changes of SNc neurons were analyzed by Nissl staining and DNA in situ end-labeling.Through extracellular recording of single neuron discharges and microelectrophoresis,the causes of and changes in SNc excitability during STN-DBS were analyzed,and the protective effect and potential mechanism of action of STN-DBS on SNc neurons in PD rats was investigated.Results SNc neuron apoptosis was significantly decreased(P<0.05)in the stimulation group,compared with the sham stimulation PD group.Spontaneous discharges of SNc neurons were observed in normal rats and PD model rats,and the mean frequency of spontaneous discharges of SNc neurons in normal rats((40.65±11.08)Hz)was higher than that of residual SNc neurons in PD rats((36.71±9.23)Hz).Electrical stimulation of the STN in rats was associated with elevated excitation in unilateral SNc neurons.However,administering the gamma-aminobutyric acid receptor blocker

  2. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic change...

  3. Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells.

    Science.gov (United States)

    Miyamoto, K; Matsunaga, T; Takemoto, N; Sanae, F; Koshiura, R

    1985-05-01

    The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.

  4. Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats

    OpenAIRE

    Mizumori, Misa; Akiba, Yasutada; Kaunitz, Jonathan D.

    2009-01-01

    Background Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. Aim The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO3 − secretion (DBS). Methods Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1–10 μM). We measured DBS with flow-through pH and CO2...

  5. DARPP-32 expression in rat brain after electroconvulsive stimulation.

    Science.gov (United States)

    Rosa, Daniela V F; Souza, Renan P; Souza, Bruno R; Motta, Bernardo S; Caetano, Fernando; Jornada, Luciano K; Feier, Gustavo; Gomez, Marcus V; Quevedo, João; Romano-Silva, Marco A

    2007-11-07

    Although electroconvulsive therapy (ECT) has been used as a treatment for mental disorder since 1930s, little progress has been made in the mechanisms underlying its therapeutic or adverse effects. The aim of this work was to analyze the expression of DARPP-32 (a protein with a central role in dopaminergic signaling) in striatum, cortex, hippocampus and cerebellum of Wistar rats subjected to acute or chronic electroconvulsive stimulation (ECS). Rats were submitted to a single stimulation (acute) or to a series of eight stimulations, applied one every 48 h (chronic). Animals were killed for collection of tissue samples at time zero, 0.5, 3, 12, 24 and 48 h after stimulation in the acute model and at the same time intervals after the last stimulation in the chronic model. Our results indicated that acute ECS produces smaller changes in the expression of DARPP-32 but, interestingly, chronic ECS increased transient expression of DARPP-32 in several time frames, in striatum and hippocampus, after the last stimulation. Results on the expression of proteins involved in signaling pathways are relevant for neuropsychiatric disorders and treatment, in particular ECT, and can contribute to shed light on the mechanisms related to therapeutic and adverse effects.

  6. Erythropoietin stimulates patellar tendon healing in rats.

    Science.gov (United States)

    Uslu, Mustafa; Kaya, Ertuğrul; Yaykaşlı, Kürşat Oğuz; Oktay, Murat; Inanmaz, Mustafa Erkan; Işık, Cengiz; Erdem, Havva; Erkan, Melih Engin; Kandiş, Hayati

    2015-12-01

    Erythropoietin (EPO), regulating erythropoiesis, is used to provide protective and regenerative activity in non-haematopoietic tissues. There is insufficient knowledge about the role of EPO activity in tendon healing. Therefore, we investigated the effect of EPO treatment on healing in rat patellar tendons. One hundred and twenty-six, four-month-old male Sprague-Dawley rats were randomly assigned to three experimental groups: 1, no treatment; 2, treatment with isotonic saline (NaCl) and 3, treatment with EPO. Each group was randomly subdivided into two groups for sacrifice at three (1a, 2a, 3a) or six weeks (1b, 2b, 3b). Complete incision of the left patellar tendon from the distal patellar pole was performed. We applied body casts for 20 days after the incised edges of the patellar tendon were brought together with a surgical technique. Both legs were harvested and specimens from each group underwent histological, biomechanical, and protein mRNA expression analyses. There were statistically significant differences in the ultimate breaking force between the EPO group and others at both weeks three and six (prats compared to the control groups biomechanically, histopathologically and with tissue protein mRNA expression. This is the first experimental study to analyze the relationship between EPO treatment and the patellar tendon repair process by biomechanical, histopathological, and tendon tissue mRNA expression methodologies. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Compensation for injury potential by electrical stimulation after acute spinal cord injury in rat.

    Science.gov (United States)

    Zhang, Guanghao; Wang, Aihua; Zhang, Cheng; Wu, Changzhe; Bai, Jinzhu; Huo, Xiaolin

    2013-01-01

    Injury potential, a direct current potential difference between normal section and the site of injury, is a significant index of spinal cord injury. However, its importance has been ignored in the studies of spinal cord electrophysiology and electrical stimulation (ES). In this paper, compensation for injury potential is used as a criterion to adjust the intensity of stimulation. Injury potential is modulated to slightly larger than 0 mV for 15, 30 and 45 minutes immediately after injury by placing the anodes at the site of injury and the cathodes at the rostral and caudal section. Injury potentials of all rats were recorded for statistical analysis. Results show that the injury potentials acquired after ES are higher than those measured from rats without stimulation and much lower than the initial amplitude. It is also observed that the stimulating voltage to keep injury potential be 0 remain the same. This phenomenon suggests that repair of membrane might occur during the period of stimulation. It is also suggested that a constant voltage stimulation can be applied to compensate for injury potential.

  8. The natural PPAR agonist linoleic acid stimulated insulin release in the rat pancreas.

    Science.gov (United States)

    Lai, Min-Chuan; Teng, Tzu-Hua; Yang, Chi

    2013-11-01

    Free fatty acids play an important role in regulating animal insulin secretion response. Acute elevated free fatty acids increased animal insulin secretion and glucose-stimulated insulin secretion. In the present study, we perfused the rat pancreas to explore the effect of unsaturated fatty acids on insulin secretion. The results showed that linoleic acid, γ-linolenic acid and arachidonic acid significantly stimulated insulin secretion. Glucose (10 mM) alone induced a biphasic insulin secretion response. The peak effluent insulin concentrations increased by 444% and 800% compared with the baseline in the first and second insulin secretion phases, respectively. Based on comparison of the percentage increases, arachidonic acid, γ-linolenic acid or linoleic acid increased glucose-induced insulin release by 555% and 934%, 522% and 995% and 463% and 1,105% in the first and second insulin secretion phases, respectively. However, the percentage increases of insulin secretion decreased significantly to 402% and 564% in the first and second phases in the rats fed a high-fat diet for 13 weeks. Linoleic acid alone stimulated a 391% increase in the peak insulin concentration compared with the baseline in the rats fed a normal diet. The peak insulin concentration decreased significantly to 183% in the rats fed a long-term high-fat diet. All the results suggested that unsaturated fatty acids stimulated insulin secretion and additively increased glucose-induced insulin secretion in the perfused rat pancreas. However, the rats fed a high-fat diet had a decreased linoleic acid-induced insulin secretion response.

  9. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats

    Directory of Open Access Journals (Sweden)

    Chun Lei Li

    2014-01-01

    Full Text Available Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, P<0.001 and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P<0.001 in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.

  10. Pudendal nerve latency time in normal women via intravaginal stimulation

    Directory of Open Access Journals (Sweden)

    Geraldo A. Cavalcanti

    2006-12-01

    Full Text Available INTRODUCTION & OBJECTIVES: Studies of motor conduction for the efferent functional assessment of the pudendal nerve in women with pelvic dysfunctions have been conducted through researching distal motor latency times. The transrectal approach has been the classic approach for this electrophysiological examination. The objective of the present study is to verify the viability of the transvaginal approach in performing the exam, to establish normal values for this method and to analyze the influence of age, stature and parity in the latency value of normal women. MATERIALS AND METHODS: A total of 23 volunteers without genitourinary pathologies participated in this study. In each, pudendal motor latency was investigated through the transvaginal approach, which was chosen due to patient’s higher tolerance levels. RESULTS: The motor response represented by registering the M-wave was obtained in all volunteers on the right side (100% and in 13 volunteers on the left side (56.5%. The mean motor latency obtained in the right and left was respectively: 1.99 ± 0.41 and 1.92 ± 0.48 milliseconds (ms. There was no difference between the sides (p = 0.66. Latency did not correlate with age, stature or obstetric history. The results obtained in the present study were in agreement with those found by other researchers using the transrectal approach. CONCLUSION: The vaginal approach represents an alternative for pudendal nerve distal motor latency time, with similar results to those achieved through the transrectal approach. Normative values obtained herein might serve as a comparative basis for subsequent physiopathological studies.

  11. Early and late stimulation of ob mRNA expression in meal-fed and overfed rats.

    OpenAIRE

    Harris, R B; Ramsay, T G; Smith, S. R.; Bruch, R C

    1996-01-01

    ob protein is hypothesized to be a circulating feedback signal in the regulation of energy balance. Obese, overfed rats have high levels of ob mRNA expression and suppressed voluntary food intake, indicating the presence of a potent satiety factor. The objectives of this experiment were to determine whether feeding rats their normal daily intake in three meals, compared with ad libitum feeding, increased ob mRNA expression and to determine the degree of obesity required to stimulate expressio...

  12. Retinoic acid binding protein in normal and neopolastic rat prostate.

    Science.gov (United States)

    Gesell, M S; Brandes, M J; Arnold, E A; Isaacs, J T; Ueda, H; Millan, J C; Brandes, D

    1982-01-01

    Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.

  13. Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats.

    Science.gov (United States)

    Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin

    2016-05-01

    [Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin

  14. Prácticas para estimular el parto normal Practices to stimulate normal childbirth

    Directory of Open Access Journals (Sweden)

    Flora Maria Barbosa da Silva

    2011-09-01

    Full Text Available Este artículo lleva a una reflexión sobre las prácticas del estímulo al parto normal, con la fundamentación teórica de cada una de ellas. Las prácticas incluidas en este estudio fueron el ayuno, enemas, spray y baños de inmersión, caminatas, movimientos pélvicos y masaje. En un contexto de revalorización del parto normal, ofrecer a la mujer durante el parto opciones de comodidad basadas en evidencias puede ser una forma de preservar el curso fisiológico del parto.This article leads to a reflection about the practices of encouraging normal childbirth, with the theoretical foundation for each one of them. The practices included in this study were fasting, enema, shower and immersion baths, walking, pelvic movements and massage. In a context of revaluation of normal birth, providing evidence-based comfort options for women during childbirth can be a way to preserve the physiological course of labour.

  15. Infrared thermal imaging of rat somatosensory cortex with whisker stimulation.

    Science.gov (United States)

    Suzuki, Takashi; Ooi, Yasuhiro; Seki, Junji

    2012-04-01

    The present study aims to validate the applicability of infrared (IR) thermal imaging for the study of brain function through experiments on the rat barrel cortex. Regional changes in neural activity within the brain produce alterations in local thermal equilibrium via increases in metabolic activity and blood flow. We studied the relationship between temperature change and neural activity in anesthetized rats using IR imaging to visualize stimulus-induced changes in the somatosensory cortex of the brain. Sensory stimulation of the vibrissae (whiskers) was given for 10 s using an oscillating whisker vibrator (5-mm deflection at 10, 5, and 1 Hz). The brain temperature in the observational region continued to increase significantly with whisker stimulation. The mean peak recorded temperature changes were 0.048 ± 0.028, 0.054 ± 0.036, and 0.097 ± 0.015°C at 10, 5, and 1 Hz, respectively. We also observed that the temperature increase occurred in a focal spot, radiating to encompass a larger region within the contralateral barrel cortex region during single-whisker stimulation. Whisker stimulation also produced ipsilateral cortex temperature increases, which were localized in the same region as the pial arterioles. Temperature increase in the barrel cortex was also observed in rats treated with a calcium channel blocker (nimodipine), which acts to suppress the hemodynamic response to neural activity. Thus the location and area of temperature increase were found to change in accordance with the region of neural activation. These results indicate that IR thermal imaging is viable as a functional quantitative neuroimaging technique.

  16. [High-frequency electro-acupuncture stimulation modulates intracerebral γ-aminobutyric acid content in rat model of Parkinson's disease].

    Science.gov (United States)

    Du, Jing; Sun, Zuo-Li; Jia, Jun; Wang, Xuan; Wang, Xiao-Min

    2011-08-25

    The purpose of the present study is to observe the effect of electro-acupuncture (EA) stimulation on intracerebral neurotransmitters in a rat model of Parkinson's disease (PD), and explore the possible mechanism. We used 6-hydroxydopamine (6-OHDA) injection in medial forebrain bundle (MFB) in the right brain of Sprague Dawley (SD) rat to establish the parkinsonian rat model, and randomly divided the PD rats into model and 100 Hz EA stimulation groups (n =10 in each group). EA stimulation group received 4 courses of EA stimulation on Baihui (GV-20) and Dazhui (GV-14) acupuncture points. Moreover, ten rats were randomly selected as sham operation group, only receiving normal saline (NS) injection in MFB. Then apomorphine (APO)-induced rotational behavior in different groups was recorded, and the contents of γ-aminobutyric acid (GABA) in the brain were analyzed with high pressure/performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that model group exhibited abnormal rotational behavior with APO treatment, suggesting the successful establishment of PD model. Compared with sham operation group, model group showed increased GABA contents in cortex and striatum, as well as decreased GABA content in ventral midbrain, on the lesioned side. EA stimulation could effectively ameliorate the abnormal rotational behavior of PD rat. Compared with the model group, EA stimulation decreased the ratio of GABA content on the lesioned side to that on unlesioned side in the cortex, while increased the ratios in the striatum and cerebellum. However, there was no difference of the ratio in the ventral midbrain among three groups. These results suggest high-frequency EA stimulation significantly improves the abnormal behavior of PD rats, which may exert through enhancing the inhibitory effect of cerebellum-basal ganglia-cortical loop on motor center.

  17. The efficacy of neuromuscular electrical stimulation with alternating currents in the kilohertz frequency to stimulate gait rhythm in rats following spinal cord injury.

    Science.gov (United States)

    Kanchiku, Tsukasa; Suzuki, Hidenori; Imajo, Yasuaki; Yoshida, Yuichiro; Moriya, Atsushi; Suetomi, Yutaka; Nishida, Norihiro; Takahashi, Youhei; Taguchi, Toshihiko

    2015-10-29

    Rehabilitation facilitates the reorganization of residual/regenerated neural pathways and is key in improving motor function following spinal cord injury. Neuromuscular electrical stimulation (NMES) has been reported as being clinically effective. Although it can be used after the acute phase post-injury, the optimal stimulation conditions to improve motor function remain unclear. In this paper, we examined the effectiveness of NMES with alternating currents in the kilohertz (kHz) frequency in gait rhythm stimulation therapy. Tests were performed using 20 mature female Fischer rats. Incomplete spinal cord injuries (T9 level) were made with an IH impactor using a force of 150 kdyn, and NMES was administered for 3 days from the 7th day post-injury. The needle electrodes were inserted percutaneously near the motor point of each muscle in conscious rats, and each muscle on the left and right leg was stimulated for 15 min at two frequencies, 75 Hz and 8 kHz, to induce a gait rhythm. Motor function was evaluated using Basso, Beattie, Bresnahan (BBB) scores and three-dimensional (3D) gait analysis. Rats were divided into four groups (5 rats/group), including the NMES treatment 75-Hz group (iSCI-NMES 75 Hz), 8-kHz group (iSCI-NMES 8 kHz), injury control group (iSCI-NT), and normal group (Normal-CT), and were compared. There was no significant difference in BBB scores among the three groups. In 3D gait analysis, compared with the injury control group, the 8-kHz group showed a significant improvement in synergistic movement of both hindlimbs. We suggest that kHz stimulation is effective in gait rhythm stimulation using NMES.

  18. Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

    Science.gov (United States)

    Sudakov, S K; Bogdanova, N G

    2016-10-01

    The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

  19. Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

    Institute of Scientific and Technical Information of China (English)

    Fei Xia; Qing-yu Zhang; Yong-ping Jiang

    2011-01-01

    Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship. Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group): four groups were treated with rhG-CSFa at 500, 100,10, 1 μg/kg, respectively, and one group was treated with vehicle only to serve as the control. The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks. During the course of the chronic toxicity study, the physical status, body weight, and food consumption were monitored. Half of the rats in each group (n= 10) were sacrificed after the last rhG-CSFa administration, and the other half were sacrificed at five weeks after the last rhG-CSFa administration. Urinalyses, blood biochemistry, hematological analysis, histopathological examination, and immunological tests were performed for each of the rats. Results The hematological analyses revealed that the mean white blood cells count, neutrophils count, and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher, and these were related with the biological activity of rhG-CSFa. Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg, a dosage of 200 folds higher than the normal clinical dosage), but these abnormalities were recovered within S-week recovery period. No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

  20. Grape antioxidant dietary fiber stimulates Lactobacillus growth in rat cecum.

    Science.gov (United States)

    Pozuelo, María José; Agis-Torres, Angel; Hervert-Hernández, Deisy; Elvira López-Oliva, María; Muñoz-Martínez, Emilia; Rotger, Rafael; Goñi, Isabel

    2012-02-01

    The digesta is a highly active biological system where epithelial cells, microbiota, nondigestible dietary components, and a large number of metabolic products interact. The gut microbiota can be modulated by both endogenous and exogenous substrates. Undigested dietary residues are substrates for colonic microbiota and may influence gut microbial ecology. The objective of this work was to study the capacity of grape antioxidant dietary fiber (GADF), which is rich in polyphenols, to modify the bacterial profile in the cecum of rats. Male adult Wistar rats were fed for 4 wk with diets containing either cellulose or GADF as dietary fiber. The effect of GADF on bacterial growth was evaluated in vitro and on the cecal microbiota of rats using quantitative real time polymerase chain reaction (RT-PCR). The results showed that GADF intake stimulates proliferation of Lactobacillus and slightly affects the composition of Bifidobacterium species. GADF was also found to have a stimulative effect on Lactobacillus reuteri and Lactobacillus acidophilus in vitro. These findings suggest that the consumption of a diet rich in plant foods with high dietary fiber and polyphenol content may enhance the gastrointestinal health of the host through microbiota modulation. Grape antioxidant fiber combines nutritional and physiological properties of dietary fiber and natural antioxidants from grapes. Grape antioxidant fiber could be used as an ingredient for functional foods and as a dietary supplement to increase the intake of dietary fiber and bioactive compounds. © 2012 Institute of Food Technologists®

  1. A remote constant current stimulator designed for rat-robot navigation.

    Science.gov (United States)

    Chen, Xi; Xu, Kedi; Ye, Shuming; Guo, Songchao; Zheng, Xiaoxiang

    2013-01-01

    In this paper, a remote stimulator is developed for rat-robot navigation based on the technique of Brain-Computer-Interface (BCI). The stimulator can output constant current from 0 to 1000 µA, which overcome several shortages of our previous constant voltage stimulator. The constant current stimulator consists of four major components, including power supply, micro control unit (MCU), constant current source and bluetooth transceiver for downloading stimulation commands. The stimulator has a weight of about 20 g and size of 32 mm*25 mm*6mm. It has five channels of stimulation, which are connected with implanted microelectrodes in rat brain. The electrical parameters were characterized on three rats with different recovery time after brain surgery. Increasing current stimulations were applied on the dorsolateral periaqueductal gray (dlPAG) area to prove the effect of current stimulation on rat behavior.

  2. Reinforcing properties of Pramipexole in normal and parkinsonian rats.

    Science.gov (United States)

    Engeln, Michel; Ahmed, Serge H; Vouillac, Caroline; Tison, François; Bezard, Erwan; Fernagut, Pierre-Olivier

    2013-01-01

    Striatal D2 and D3 dopamine receptors are involved in mediating the reinforcing properties of natural rewards and drugs. In Parkinson's disease, while D2/3 dopamine agonists alleviate motor symptoms, behavioral addictions and withdrawal syndrome are reported in up to 15% of patients. The origin of such adverse effects is poorly understood but suggests that D2/3 agonists could possess reinforcing properties. We evaluated the reinforcing properties of the widely used D2/3 agonist, Pramipexole (PPX), in normal and parkinsonian rats. Intracerebroventricular injections of 6-OHDA induced a bilateral loss of tyrosine hydroxylase-positive cells in the substantia nigra (-51%) and ventral tegmental area (-31%). The animals were then allowed to self-administer intravenous PPX under fixed ratio and progressive ratio (PR) reinforcement schedules before being tested for extinction of PPX seeking. While parkinsonian were slower than sham rats in acquiring self-administration behavior, they later reached the same level of intake. The reinforcing value of PPX, as assessed during PR and extinction, was moderate in both groups. PPX heightened ∆FosB expression in dorsal striatum of lesioned rats and similar PR results involved different striatal subregions between groups. Altogether, our results show that drug-naïve rats self-administer PPX and that the dopaminergic lesion does not affect its reinforcing effects. While PPX reinforcing value was moderate in most rats, a subset of animals displayed a high number of responses and appeared to be particularly sensitive to this drug. These data suggest that PPX may not be responsible for the reported side-effects but rather call for further investigating the differential vulnerability among individuals.

  3. Changes in growth factor expression in normal aging of the rat retina.

    Science.gov (United States)

    Smith, Christopher P; Steinle, Jena J

    2007-12-01

    Although much is known about the growth factor changes in ocular tissues during various diseases, little is known about normal aging of the retina. In order to further understand normal aging in the retina, we characterized age-related changes of growth factor expression in three different ages of rat retina. Real time PCR and protein analysis was conducted to investigate steady state mRNA expression and protein levels of VEGF, VEGFR2, PEDF, Ang-1, Tie-2, EphB4 and ephrinB2 in the retina of 8-, 22-, and 32-month-old Brown Norway X Fischer 344 F1 hybrid rats. An increase of VEGF protein levels was found at 32months compared to 8 and 22months of age. VEGFR2 protein was found to be increased at 22 and 32months compared to 8months. PEDF protein levels were reduced at 22 and 32months. Tie-2 levels were found to be significantly decreased by 32months compared to 8months of age, while ephrinB2 was found to be significantly lower at both 22 and 32months compared to 8months of age. The increases found in VEGF and its receptor VEGFR2, with the simultaneous decrease of PEDF protein levels, may stimulate an environment that is well suited for neovascularization in the normal aging retina. Overall, these results suggest that normal aging produces substantial changes in gene expression and protein levels.

  4. Effect of Low-Level Laser Stimulation on EEG Power in Normal Subjects with Closed Eyes

    Directory of Open Access Journals (Sweden)

    Jih-Huah Wu

    2013-01-01

    Full Text Available In a previous study, we found that the low-level laser (LLL stimulation at the palm with a frequency of 10 Hz was able to induce significant brain activation in normal subjects with opened eyes. However, the electroencephalography (EEG changes to LLL stimulation in subjects with closed eyes have not been studied. In the present study, the laser array stimulator was applied to deliver insensible laser stimulations to the palm of the tested subjects with closed eyes (the laser group. The EEG activities before, during, and after the laser stimulation were collected. The EEG amplitude powers of each EEG frequency band at 19 locations were calculated. These power data were then analyzed by SPSS software using repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced decrease in the EEG power in alpha-bandwidth during laser simulation and then less decrease in the EEG power in delta-bandwidth in normal subjects with laser stimulation. The EEG power in beta-bandwidth in the right occipital area also decreased significantly in the laser group. We suggest that LLL stimulation might be conducive to falling into sleep in patients with sleep problems.

  5. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    , ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P < 0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P > 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

  6. Stimulation of contacts in ventral but not dorsal subthalamic nucleus normalizes response switching in Parkinson's disease.

    Science.gov (United States)

    Greenhouse, Ian; Gould, Sherrie; Houser, Melissa; Aron, Adam R

    2013-06-01

    Switching between responses is a key executive function known to rely on the frontal cortex and the basal ganglia. Here we aimed to establish with greater anatomical specificity whether such switching could be mediated via different possible frontal-basal-ganglia circuits. Accordingly, we stimulated dorsal vs. ventral contacts of electrodes in the subthalamic nucleus (STN) in Parkinson's patients during switching performance, and also studied matched controls. The patients underwent three sessions: once with bilateral dorsal contact stimulation, once with bilateral ventral contact stimulation, and once Off stimulation. Patients Off stimulation showed abnormal patterns of switching, and stimulation of the ventral contacts but not the dorsal contacts normalized the pattern of behavior relative to controls. This provides some of the first evidence in humans that stimulation of dorsal vs. ventral STN DBS contacts has differential effects on executive function. As response switching is an executive function known to rely on prefrontal cortex, these results suggest that ventral contact stimulation affected an executive/associative cortico-basal ganglia circuit.

  7. Comparative analysis between thoracic spinal cord and sacral neuromodulation in a rat spinal cord injury model: a preliminary report of a rat spinal cord stimulation model.

    Science.gov (United States)

    Hyun, Seung-Jae; Lee, Chang-Hyun; Kwon, Ji Woong; Yoon, Cheol-Yong; Lim, Jae-Young; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2013-03-01

    The purpose of this study is to compare a neuroprotective effect of thoracic cord neuromodulation to that of sacral nerve neuromodulation in rat thoracic spinal cord injury (SCI) model. Twenty female Sprague Dawley rats were randomly divided into 4 groups: the normal control group (n=5), SCI with sham stimulation group (SCI, n=5), SCI with electrical stimulation at thoracic spinal cord (SCI + TES, n=5), and SCI with electrical stimulation at sacral nerve (SCI + SES, n=5). Spinal cord was injured by an impactor which dropped from 25mm height. Electrical stimulation was performed by the following protocol: pulse duration, 0.1ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration at thoracic epidural space and S2 or 3 neural foramina for 4 weeks. Locomotor function, urodynamic study, muscle weights, and fiber cross sectional area (CSA) were investigated. All rats of the SCI + TES group expired within 3 days after the injury. The locomotor function of all survived rats improved over time but there was no significant difference between the SCI and the SCI + SES group. All rats experienced urinary retention after the injury and recovered self-voiding after 3-9 days. Voiding contraction interval was 25.5±7.5 minutes in the SCI group, 16.5±5.3 minutes in the SCI+SES group, and 12.5±4.2 minutes in the control group. The recovery of voiding contraction interval was significant in the SCI + SES group comparing to the SCI group (pspinal cord stimulation model. However, sacral neuromodulation have a therapeutic potential to improve neurogenic bladder and muscle atrophy.

  8. Imaging neurovascular function and functional recovery after stroke in the rat striatum using forepaw stimulation

    Science.gov (United States)

    Shih, Yen-Yu Ian; Huang, Shiliang; Chen, You-Yin; Lai, Hsin-Yi; Kao, Yu-Chieh Jill; Du, Fang; Hui, Edward S; Duong, Timothy Q

    2014-01-01

    Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP–CBV correlation was found in the ipsilateral and contralateral sensory cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r=0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (PfMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats. PMID:24917039

  9. Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid.

    Science.gov (United States)

    Conti, A; Studer, H

    1977-05-01

    The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation.

  10. Changes in muscular strength and electromyogram in rats with muscular disuse atrophy following electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Lü; Xuanming Hao

    2006-01-01

    BACKGROUND: Atrophy of skeletal muscle is found under the condition of muscular disuse or in the process of fixation. It is affected by fixation, and electromyogram (EMG) discharge and muscular strength levels will be significantly decreased with accelerating tendency. Electrical stimulation (ES) therapy can release the velocity of muscular disuse atrophy effectively, so it is an effective method for preventing and treating muscular disuse atrophy and accelerating rehabilitation velocity following removal of fixation.OBJECTIVE: To observe the effect of ES therapy at different time points following the fixation of rat models of muscular disuse atrophy on muscular strength and EMG of quadriceps femoris.DESIGN: A randomized and controlled animal experiment.SETTING: Department of Rehabilitation and Physiotherapy, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA; College of Sports Science, South China Normal University.MATERIALS: Male SD rats, of clean grade, aged 4 months old, weighing (230±10) g, were provided by the Animal Experimental Center of Sun Yat-sen University. EMG measurement and analysis system (NEC Company, Japan) and four-channel recorder (NEC Company, Japan) were used in this experiment.METHODS: This experiment was carried out in the Laboratory of Human Sports Science, South China Normal University between September 2003 and March 2004. Totally 125 successful SD rat models of muscular disuse atrophy were randomly divided into 5 groups with 25 rats in each by a lot: normal control group, in which, the rats were untouched; ES 24 hours, 1, 2 and 3 weeks groups: the knees of rats in these four groups were fixed. Rats in four groups underwent ES therapy at 24 hours, 1, 2 and 3 weeks after fixation. T90- Ⅱ computer ES muscular strength training instrument was used in ES therapy every other day. The instrument was set as square wave,5 mA current intensity and 10 minutes a day. Muscular strength of quadriceps femoris and data of

  11. Stimulatory and inhibitory effects of forskolin on adenylate cyclase in rat normal hepatocytes and hepatoma cells.

    Science.gov (United States)

    Miyamoto, K; Sanae, F; Koshiura, R; Matsunaga, T; Takagi, K; Satake, T; Hasegawa, T

    1989-02-01

    Forskolin synergistically potentiated adenosine 3',5'-cyclic monophosphate formation by prostaglandin E1 (PGE1) in rat normal hepatocytes freshly prepared by collagenase digestion and rat ascites hepatoma AH66 cells, but dose-dependently inhibited the accumulation by PGE1 in AH66F cells. Forskolin activated adenylate cyclase in a dose-dependent manner in homogenates of all cell lines. In normal hepatocytes and AH66 cells, simultaneous addition of forskolin and other adenylate cyclase activators [isoproterenol (IPN), PGE1, guanosine 5'-triphosphate sodium salt (GTP), 5'-guanylylimidodiphosphate sodium salt (Gpp (NH)p), NaF, cholera toxin, islet activating protein and MnCl2] gave greater than additive responses. On the other hand, in AH66F cells, the effect of forskolin on adenylate cyclase was hardly influenced by GTP, but forskolin diminished the activities induced by high concentrations of GTP to that by the diterpene alone. Forskolin also significantly inhibited the PGE1-stimulated and the guanine nucleotide binding regulatory protein-stimulated activities. Because AH66F cells were insensitive to IPN, the combination with forskolin and IPN gave similar activity to that obtained with the diterpene alone. The effect of forskolin on the activation by manganese ion was neither synergistic nor inhibitory but was additive in AH66F cells. These results suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide binding regulatory protein and the catalytic unit in normal hepatocytes and AH66 cells, but in AH66F cells forskolin interferes with the coupling of the two components of adenylate cyclase.

  12. Optimal Vagus Nerve Stimulation Frequency for Suppression of Spike-and-Wave Seizures in Rats.

    Science.gov (United States)

    Jiao, Jianhang; Harreby, Kristian R; Sevcencu, Cristian; Jensen, Winnie

    2016-06-01

    Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug-resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10-30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike-and-wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9-21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130-180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today.

  13. Quantitative test of responses to thermal stimulation in spinally injured rats using a Peltier thermode: a new approach to study cold allodynia.

    Science.gov (United States)

    Gao, Tianle; Hao, Jing-Xia; Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun

    2013-01-30

    In this work, we described a method of testing of responses of spinally injured rats to thermal stimulation (heating and cooling) to the flank area using a Peltier thermode. With a baseline holding temperature at 32°C and the temperature change rate of 0.5°C/s, we measured vocalization thresholds of rats to thermal stimulation in the flank area. While normal rats did not vocalize to temperatures changes ranging from 6°C to 50°C, the spinally injured rats exhibited significantly increased response to cooling with average response temperature above 15°C through the 70 day observation period after spinal cord injury. The response temperature to cooling in spinally injured rats is correlated with the magnitude of responses to cold stimulation scored after ethyl chloride spray and with the response threshold to mechanical stimulation. In contrast, we did not observe an increase in response to warm/heat stimuli. The results showed that ischemic spinal cord injury produced cold, but not heat, allodynia in rats. Furthermore, we showed that it is possible to quantitatively measure response of rats to thermal stimulation on the body using temperature as end points which may aid further studies on mechanisms and treatments of thermal stimulation, particularly cold, evoked pain.

  14. RPE cell surface proteins in normal and dystrophic rats

    Energy Technology Data Exchange (ETDEWEB)

    Clark, V.M.; Hall, M.O.

    1986-02-01

    Membrane-bound proteins in plasma membrane enriched fractions from cultured rat RPE were analyzed by two-dimensional gel electrophoresis. Membrane proteins were characterized on three increasingly specific levels. Total protein was visualized by silver staining. A maximum of 102 separate proteins were counted in silver-stained gels. Glycoproteins were labeled with 3H-glucosamine or 3H-fucose and detected by autoradiography. Thirty-eight fucose-labeled and 61-71 glucosamine-labeled proteins were identified. All of the fucose-labeled proteins were labeled with glucosamine-derived radioactivity. Proteins exposed at the cell surface were labeled by lactoperoxidase-catalyzed radioiodination prior to preparation of membranes for two-dimensional analysis. Forty separate 125I-labeled surface proteins were resolved by two-dimensional electrophoresis/autoradiography. Comparison with the glycoprotein map showed that a number of these surface labeled proteins were glycoproteins. Two-dimensional maps of total protein, fucose-labeled, and glucosamine-labeled glycoproteins, and 125I-labeled surface proteins of membranes from dystrophic (RCS rdy-p+) and normal (Long Evans or RCS rdy+p+) RPE were compared. No differences in the total protein or surface-labeled proteins were observed. However, the results suggest that a 183K glycoprotein is more heavily glycosylated with glucosamine and fucose in normal RPE membranes as compared to membranes from dystrophic RPE.

  15. Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

    Science.gov (United States)

    Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

    2004-03-01

    Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

  16. Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer's disease rat.

    Science.gov (United States)

    Liu, Zhi-Bin; Niu, Wen-Min; Yang, Xiao-Hang; Wang, Yuan; Wang, Wei-Gang

    2010-12-01

    To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P 0.05). Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

  17. Dopaminergic stimulation of subthalamic nucleus elicits oral dyskinesia in rats.

    Science.gov (United States)

    Parry, T J; Eberle-Wang, K; Lucki, I; Chesselet, M F

    1994-08-01

    The effects of dopaminergic stimulation of the subthalamic nucleus (STh) on motor behavior were examined in conscious rats. Unilateral infusion of apomorphine (0.1 to 3.2 micrograms) into the STh induced a dose-dependent increase in abnormal, nondirected orofacial movements without altering turning, sniffing, grooming, or rearing behaviors. Orofacial movements elicited by local infusion of apomorphine (1.0 microgram) into the STh were blocked by peripheral administration of the D1 antagonist, SCH 23390 (0.1 mg/kg, sc), but not by the D2 antagonists haloperidol (1.0 mg/kg, sc) or sulpiride (50 mg/kg, sc). Furthermore, coinfusion of SCH 23390 (1.0 microgram), but not sulpiride (5.0 micrograms), with apomorphine (1.0 microgram) into the STh blocked oral dyskinesia. Oral movements could not be reelicited by an infusion of apomorphine into the STh after a kainic acid lesion of the STh. In addition, infusion of apomorphine (1.0 microgram) into sites proximal to but deliberately outside of the STh failed to elicit nondirected oral movements above baseline levels. The results indicate that stimulation of D1 dopaminergic receptors within the STh induces abnormal orofacial movements. This highlights the importance of the dopaminergic input to the STh in the regulation of motor function and suggests that D1 receptor antagonists could prove useful in the treatment of orofacial dyskinesia in humans.

  18. Atorvastatin and whisker stimulation synergistically enhance angiogenesis in the barrel cortex of rats following focal ischemia.

    Science.gov (United States)

    Zhang, Yunyun; Huang, Susu; Wang, Bin; Sun, Bo; Li, Wenlei; Lu, Xiaowei; Ding, Xinsheng

    2012-09-13

    Physical therapy can promote neurovascular plasticity and functional recovery after CNS disorders such as ischemic stroke. We have previously demonstrated that whisker stimulation promotes angiogenesis in the penumbra of the ischemic barrel cortex. The aim of this study was to examine whether atorvastatin and whisker stimulation can act synergistically in enhancing angiogenesis in the barrel cortex following ischemia. Rats were divided into sham-operation, control, atorvastatin-treatment, whisker stimulation and combination therapy groups. And they were trained continuously for 10 trials per half day until the rat fulfilled 80% correct choices for continuous thirty trials, which were considered to reach the criteria. The number was significantly less in the combination therapy group than that in the whisker stimulation group (Pwhisker stimulation (Pwhisker stimulation in rats and amplify post-ischemic angiogenesis induced by whisker stimulation, potentially via enhanced expression of VEGF and BDNF in the peri-infarct region. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    Science.gov (United States)

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation.

  20. Effect of scorpion toxin on the enterochromaffin-like cells in normal and Trypanosoma cruzi-infected rats: a morphological study

    Directory of Open Access Journals (Sweden)

    N. H. Toppa

    1989-02-01

    Full Text Available Intravenous injection of scorpion toxin (Tityus serrulatus in normal and Trypanosoma cruzi infected rats did not cause ultrastructural morphologic changes on enterochromaffin-like (ECL cells of the stomach, although it induced a significant increase of the gastric secretion. Our data seem to indicate that gastric ECL cells structure is not affected by stimulation with scorpion toxin or by acute infection with T. cruzi in the rat.

  1. Effects of Ficus asperifolia on normal rat estrus cyclicity

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  2. Suppression of angiotensin II stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Functional responses to angiotensin II(AT-II) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats.Our data showed that AT-II-stimulated extracellular acidification rate (ECAR),which was measured by Cytosesor microphysiometry,was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals.The ability of AT-II to promote formation of inositol phosphates,the second messenger produced by the activation of Gq-coupled receptors,was also considerably suppressed in the cirrhotic VSMCs.Furthermore,the maximal p42/44 MAPK phosphorylation stimulated by AT-II was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs.Taken together,our data clearly demonstrated that the functional responses to AT-II was severely suppressed in aortic VSMCs in cirrhosis,indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

  3. Encode the "STOP" command by photo-stimulation for precise control of rat-robot.

    Science.gov (United States)

    Chen, Sicong; Qu, Yi; Guo, Songchao; Shi, Zhaoyue; Xu, Kedi; Zheng, Xiaoxiang

    2013-01-01

    Studies on behavior control are important for bio-robots designation. For auto or manual navigation of the bio-robots, the accuracy of the command execution is especially critical. In this paper, we reported a precise "STOP" command for the rat-robots by optical stimulation of the central nervous system (CNS). We labeled dorsolateral periaqueductal gray (dlPAG) neurons with light sensitive channelrhodopsin-2 (ChR2) and directly probed the optical fiber to reactivate these neurons. The rats showed freezing behavior only upon the optical stimulation with an appropriate range of laser intensity and stimulation frequency. Neuron spikes and local field potential (LFP) were simultaneously recorded with optical stimulation by optrodes on free moving rat-robots. Together, our findings demonstrated the utility of deep brain optical stimulation for the stopping behavior of rat-robot control and indicated a potential application of optogenetics for precise control of bio-robots in further work.

  4. Difference in leptin hormone response to nutritional status in normal adult male albino rats.

    Science.gov (United States)

    Al-Sowyan, Noorah S

    2009-01-15

    The present study investigated the effect of 14 days diet, enriched in butter, vitamin E (vit. E) and green tea, on the major regulators of energy expenditure. Leptin is the product OB gene. This 16 KDa protein is produced by mature adipocytes and is secreted in plasma. Its plasma levels are strongly correlated with adipose mass in rodents as well as in humans. Leptin inhibit food intake, reduces body weight and stimulates energy expenditure. In order to evaluate the effect of diet enriched in butter, vit. E and green tea on body weight, adipose tissue weight and organs weight, serum lipids, lipoproteins content and serum leptin levels in male albino rats supplemented for 14 days on the previous diet. This study showed that high fat diet significantly increased body weight and adipose tissue weight, while vit. E and green tea enriched diet significantly lowered body weight and adipose tissue weight, kidney and spleen weights didn't show significant changes in all the experimental groups. While liver weight decreased in diet supplemented with high fat diet. Also, the results showed that high fat diet and vit. E supplemented diet induced significant increase in total cholesterol, LDLc., triglyceride level with significant decrease in HDLc. level as compared to normal control rats. Finally green tea supplemented diet induced significant decrease in total cholesterol, LDLc., triglyceride level with insignificant increase in HDLc. level in control rats. On the other hand, high fat supplemented diet significantly increased serum leptin levels in rats compared to control group, while vit. E and green tea enriched diet significantly lowered serum leptin levels at the end of experimental period. In conclusion, improving the biological activity of leptin by diet modification may exist as a practical strategy for the treatment of obesity and related disorders and a diet rich in green tea to reduce the risk of cardiovascular disease (CVD) obesity and also protect the liver

  5. Topography of synchronization of somatosensory evoked potentials elicited by stimulation of the sciatic nerve in rat

    Directory of Open Access Journals (Sweden)

    Xuefeng eQu

    2016-05-01

    Full Text Available Purpose: Traditionally, the topography of somatosensory evoked potentials (SEPs is generated based on amplitude and latency. However, this operation focuses on the physical morphology and field potential-power, so it suffers from difficulties in performing identification in an objective manner. In this study, measurement of the synchronization of SEPs is proposed as a method to explore brain functional networks as well as the plasticity after peripheral nerve injury. Method: SEPs elicited by unilateral sciatic nerve stimulation in twelve adult male Sprague-Dawley (SD rats in the normal group were compared with SEPs evoked after unilateral sciatic nerve hemisection in four peripheral nerve injured SD rats. The characterization of synchronized networks from SEPs was conducted using equal-time correlation, correlation matrix analysis, and comparison to randomized surrogate data. Eigenvalues of the correlation matrix were used to identify the clusters of functionally synchronized neuronal activity, and the participation index (PI was calculated to indicate the involvement of each channel in the cluster. The PI value at the knee point of the PI histogram was used as a threshold to demarcate the cortical boundary. Results: Ten out of the twelve normal rats showed only one synchronized brain network. The remaining two normal rats showed one strong and one weak network. In the peripheral nerve injured group, only one synchronized brain network was found in each rat. In the normal group, all network shapes appear regular and the network is largely contained in the posterior cortex. In the injured group, the network shapes appear irregular, the network extends anteriorly and posteriorly, and the network area is significantly larger. There are considerable individual variations in the shape and location of the network after peripheral nerve injury. Conclusion: The proposed method can detect functional brain networks. Compared to the results of the

  6. Antihyperglycemic and Antihyperlipidemic Activity of Plectranthus Amboinicus on Normal and Alloxan-Induced Diabetic Rats

    OpenAIRE

    Viswanathaswamy, A.H.M.; Koti, B. C.; Aparna Gore; Thippeswamy, A. H. M.; Kulkarni, R. V.

    2011-01-01

    The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied...

  7. Effect of telmisartan on VEGF-induced and VEGF-independent angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ)-induced diabetic rats.

    Science.gov (United States)

    Chaudagar, Kiranj K; Mehta, Anita A

    2014-01-01

    Telmisartan possesses endothelial protective effects due to angiotensin II type 1 receptor antagonist, peroxisome proliferator-activated receptor γ (PPARγ) agonist and antioxidant action. Therefore, our objective was to study effect of telmisartan on angiogenic responsiveness of coronary endothelial cells (cECs) of normal and diabetic rats. Male Wistar rats were divided into six groups, normal rats, diabetic rats 30 d. (30 days after administration of STZ), diabetic rats 60 ds. (60 days after administration of STZ), telmisartan-treated normal rats (2 mg/kg, p.o., for 15 days before isolation of hearts), telmisartan-treated diabetic rats 30 ds, and telmisartan-treated diabetic rats 60 ds. Each group was further divided into two subgroups, sham rat hearts and ischemia-reperfused rat hearts. After isolation of cEC from each subgroup, angiogenic responsiveness and nitric oxide releasing properties were studied using chorioallantoic membrane (CAM) assay and Griess method, respectively. cEC of normal rats showed significant increase in angiogenic responsiveness in presence of vascular endothelial growth factor (VEGF) but not in absence of it. This activity was attenuated by pretreatment of cEC with l-NAME, wortmannin and chelerythrine. Diabetes and ischemia reperfusion injury suppressed angiogenic responsiveness of cEC. Telmisartan treatment showed significant increase in VEGF-induced angiogenic responsiveness and nitric oxide releasing properties of cECs of all subgroups as compared to their respective non-treated subgroups. These effects of telmisartan were significantly inhibited by pretreatment of cECs with L-NAME and wortmannin but not with chelerythrine. Our data suggest that telmisartan improves VEGF-induced coronary angiogenic activity in normal and diabetic rats via stimulation of PI3K/eNOS/NO pathway.

  8. Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

    Science.gov (United States)

    Chan, Leanne L H; Lee, Eun-Jin; Humayun, Mark S; Weiland, James D

    2011-06-01

    Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84-782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-μm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats (P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.

  9. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

    Directory of Open Access Journals (Sweden)

    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  10. Cortical stimulation and tooth pulp evoked potentials in rats: a model of direct anti-nociception.

    Science.gov (United States)

    Rusina, Robert; Barek, Stephane; Vaculin, Simon; Azérad, Jean; Rokyta, Richard

    2010-01-01

    While the effect of cortex stimulation on pain control is widely accepted, its physiological basis remains poorly understood. We chose an animal model of pain to study the influence of sensorimotor cortex stimulation on tooth pulp stimulation evoked potentials (TPEPs). Fifteen awake rats implanted with tooth pulp, cerebral cortex, and digastric muscle electrodes were divided into three groups, receiving 60 Hz, 40 Hz and no cortical stimulation, respectively. TPEPs were recorded before, one, three and five hours after continuous stimulation. We observed an inverse relationship between TPEP amplitude and latency with increasing tooth pulp stimulation. The amplitudes of the early components of TPEPs increased and their latency decreased with increasing tooth pulp stimulation intensity. Cortical stimulation decreased the amplitude of TPEPs; however, neither the latencies of TPEPs nor the jaw-opening reflex were changed after cortical stimulation. The decrease in amplitude of TPEPs after cortical stimulation may reflect its anti-nociceptive effect.

  11. NMR-based metabolomics Reveals Alterations of Electro-acupuncture Stimulations on Chronic Atrophic Gastritis Rats

    Science.gov (United States)

    Xu, Jingjing; Zheng, Xujuan; Cheng, Kian-Kai; Chang, Xiaorong; Shen, Guiping; Liu, Mi; Wang, Yadong; Shen, Jiacheng; Zhang, Yuan; He, Qida; Dong, Jiyang; Yang, Zongbao

    2017-01-01

    Chronic atrophic gastritis (CAG) is a common gastrointestinal disease which has been considered as precancerous lesions of gastric carcinoma. Previously, electro-acupuncture stimulation has been shown to be effective in ameliorating symptoms of CAG. However the underlying mechanism of this beneficial treatment is yet to be established. In the present study, an integrated histopathological examination along with molecular biological assay, as well as 1H NMR analysis of multiple biological samples (urine, serum, stomach, cortex and medulla) were employed to systematically assess the pathology of CAG and therapeutic effect of electro-acupuncture stimulation at Sibai (ST 2), Liangmen (ST 21), and Zusanli (ST 36) acupoints located in the stomach meridian using a rat model of CAG. The current results showed that CAG caused comprehensive metabolic alterations including the TCA cycle, glycolysis, membrane metabolism and catabolism, gut microbiota-related metabolism. On the other hand, electro-acupuncture treatment was found able to normalize a number of CAG-induced metabolomics changes by alleviating membrane catabolism, restoring function of neurotransmitter in brain and partially reverse the CAG-induced perturbation in gut microbiota metabolism. These findings provided new insights into the biochemistry of CAG and mechanism of the therapeutic effect of electro-acupuncture stimulations. PMID:28358020

  12. Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer's, Parkinson's and Huntington's disease.

    Science.gov (United States)

    Ljubisavljevic, M R; Ismail, F Y; Filipovic, S

    2013-07-01

    Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.

  13. Effects of Moxibustion Stimulation on the Intensity of Infrared Radiation of Tianshu (ST25 Acupoints in Rats with Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Xiaomei Wang

    2012-01-01

    Full Text Available ST25 is a key acupoint used in the treatment of ulcerative colitis by moxibustion stimulation, but the biophysical mechanism underlying its effects is still unknown. The aim of the present study was to explore the biophysical properties of ST25 acupoint stimulated by moxibustion in a rat model of ulcerative colitis. The infrared radiation intensity of fourteen wavelengths of ST25 showed significant differences between the normal and model control groups. The intensity of infrared radiation of forty wavelengths showed significant differences compared with the corresponding control points in normal rats. The intensity of infrared radiation of twenty-eight wavelengths showed significant differences compared with the corresponding control points in model rats. The intensity of infrared radiation of nine wavelengths in the herb-partition moxibustion group, eighteen wavelengths in the ginger-partition moxibustion group, seventeen wavelengths in the garlic-partition moxibustion group, and fourteen wavelengths in the warming moxibustion group of the left ST25 showed significant differences compared with that of the model control group. For the right-hand-side ST25, these values were 33, 33, 2, and 8 wavelengths, respectively. This indicated that one possible biophysical mechanism of moxibustion on ST25 in ulcerative colitis model rats might involve changes in the intensity of infrared radiation of ST25 at different wavelengths.

  14. The effects of Tremella aurantia on testosterone and corticosterone productions in normal and diabetic rats.

    Science.gov (United States)

    Lo, Hui-Chen; Yang, Jyuer-Ger; Liu, Bi-Ching; Chen, Yen-Wen; Huang, Yuan-Li; Poon, Song Ling; Liu, Ming-Yie; Huang, Bu-Miin

    2004-01-01

    Tremella aurantia (TA) has been traditionally used as food and crude medicine in Chinese society. The polysaccharide isolated from the fruiting bodies of TA exhibits significant hypoglycemic activity in diabetic mouse models of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Diabetes will cause sexual dysfunction in patients. In the present study, we examined if the treatment of TA on IDDM and NIDDM rats will restore steroidogenesis and then the reproductive function. The fruiting bodies (FB), mycelium (TM) and polysaccharide (GX) of TA were fed to the IDDM and NIDDM rats, and testosterone and corticosterone levels in plasma, the weight of steroidogenic organs, and the expression of steroidogenic acute regulatory (StAR) protein and P450scc enzyme were determined. Plasma testosterone productions were significantly suppressed with the feeding of FB or TM in normal rat (p diabetes rats (p 0.05). There was no significant difference of the testosterone production between normal and NIDDM rats (p > 0.05). In plasma corticosterone production, there were no differences among control, FB- or TM-fed normal rats (p > 0.05). Corticosterone levels were reduced in IDDM rats compared to control, and FB or TM could restore its level. Corticosterone levels were induced in NIDDM rats compared to control (p feeding in NIDDM rat had lesser testis weight compared to NIDDM rats. The expression of StAR protein and P450scc enzyme were not different among groups in IDDM and NIDDM rats. Plasma testosterone productions were suppressed in normal rats with the feeding of TA (FB and TM). IDDM rats did have lower testosterone, but not in NIDDM, and FB or TM could not restore the inhibitory effects. The induction of IDDM or NIDDM rats did affect steroidogenesis and steroidogenic organ weights, and the feeding of TA had different effects on steroidogenesis in different types of diabetic rats.

  15. Optogenetics Based Rat-Robot Control: Optical Stimulation Encodes "Stop" and "Escape" Commands.

    Science.gov (United States)

    Chen, SiCong; Zhou, Hong; Guo, SongChao; Zhang, JiaCheng; Qu, Yi; Feng, ZhouYan; Xu, KeDi; Zheng, XiaoXiang

    2015-08-01

    Electric brain stimulation is frequently used in bio-robot control. However, one possible limitation of electric stimulation is the resultant wide range of influences that may lead to unexpected side-effects. Although there has been prior research done towards optogenetics based brain activation, there has not been much development regarding the comparisons between electric and optical methods of brain activation. In this study, we first encode "Stop" and "Escape" commands by optical stimulation in the dorsal periaqueductal grey (dPAG). The rats behavioral comparisons are then noted down under these two methods. The dPAG neural activity recorded during optical stimulation suggests rate and temporal coding mechanisms in behavioral control. The behavioral comparisons show that rats exhibit anxiety under the "Stop" command conveyed through both optical and electric methods. However, rats are able to recover more quickly from freezing only under optical "Stop" command. Under "Escape" commands, also conveyed through optical means, the rat would move with lessened urgency but the results are more stable. Moreover, c-Fos study shows the optical stimulation activates restricted range in midbrain: the optical stimulation affected only dPAG and its downstreams but electric stimulation activates both the upstream and downstream circuits, in which the glutamatergic neurons are largely occupied and play important role in "Stop" and "Escape" behavior controls. We conclude that optical stimulation is more suited for encoding "Stop" and "Escape" commands for rat-robot control.

  16. Electrical stimulation vs. pulsed and continuous-wave optical stimulation of the rat prostate cavernous nerves, in vivo

    Science.gov (United States)

    Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur; Fried, Nathaniel M.

    2015-07-01

    Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.

  17. NMDAR1 mRNA expression and glutamate receptor stimulated increase in cytosolic calcium concentration in rat and mouse cerebellar granule cells

    DEFF Research Database (Denmark)

    Mogensen, H S; Jørgensen, Ole Steen

    1996-01-01

    RNA and was normalized to that of the constitutively expressed H3.3 histone mRNA. The glutamate and NMDA stimulated increase in cytosolic Ca(2+)-ion concentration was measured using the fluorescent Ca(2+)-chelator Fluo3. In contrast to the hypothesis, we found NMDAR1 mRNA expression to be lower in mouse than in rat...

  18. Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

    Science.gov (United States)

    Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

    2014-07-15

    Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

  19. Hypoglycemic effect of Chlorella vulgaris intake in type 2 diabetic Goto-Kakizaki and normal Wistar rats.

    Science.gov (United States)

    Jeong, Hyejin; Kwon, Hye Jin; Kim, Mi Kyung

    2009-01-01

    The aim of this study was to examine the hypoglycemic effect of chlorella in 6 week-old type 2 diabetic Goto-Kakizaki (GK, n=30) rats and 6 week-old normal Wistar (n=30) rats. Animals were randomly assigned to 3 groups respectively, and were fed three different experimental diets containing 0%, 3% or 5% (w/w) chlorella for 8 weeks. In diabetic GK rats, the insulinogenic-indices were not significantly different among the groups. The concentrations of fasting plasma glucagon and hepatic triglyceride, and the insulin/glucagon ratios of the GK-3% chlorella and GK-5% chlorella groups were significantly lower than those of the GK-control group. The HOMA-index and the concentrations of fasting blood glucose and plasma insulin of the GK-3% chlorella and GK-5% chlorella groups were slightly lower than those of the GK-control group. In normal Wistar rats, the insulinogenic-indices were not significantly different among the normal groups, but that of the Wistar-5% chlorella group was slightly higher than the other groups. The concentrations of fasting blood glucose and plasma insulin, and the HOMA-index of the Wistar-5% chlorella group were a little higher, and the fasting plasma glucagon concentration and the insulin/glucagon ratio of the Wistar-5% chlorella group were significantly higher than those of the Wistar-control and Wistar-3% chlorella groups. In conclusion, this study shows that the glucose-stimulated insulin secretion was not affected by the intake of chlorella, which could be beneficial, however, in improving insulin sensitivity in type 2 diabetic GK and normal Wistar rats.

  20. Differences in maturation of the jaw-opening reflex between rats that received early-and late-masticatory stimulation.

    Science.gov (United States)

    Changsiripun, C; Yabushita, T; Soma, K

    2012-12-01

    The jaw-opening reflex (JOR) plays an important role in the regulation of jaw movement during mastication. Previous study showed that altered masticatory function during growth impedes JOR maturation and thus may affect masticatory performance in adults. However, no studies have compared the benefit of early and delayed correction in terms of functional development. Therefore, this study tested the hypothesis that early-stimulation of masticatory function during growth can promote JOR maturation better than late-stimulation during adulthood. Soon after weaning, 120 female Wistar rats were divided into two groups and fed either solid (control group) or liquid (experimental group) diets. The experimental group was further divided into early-, late-, and non-stimulation subgroups. Early- and late-stimulation groups were fed a solid diet instead of a liquid diet at 5- and 11-week-old, respectively, whereas non-stimulation group was fed only a liquid diet until the end of the experiment. At 3, 5, 7, 9, 11 and 13 weeks, JOR recordings were conducted in anaesthetised rats of all groups. Latency and peak-to-peak amplitude of the JOR were compared between the groups. From 7 to 13 weeks, early-stimulation group showed a JOR with short latency and high amplitude similar to that of control group. In contrast, late- and non-stimulation groups showed significantly longer latency and smaller amplitude of the JOR than in control group. We demonstrated that early masticatory stimulation within the critical period for programming mastication may have greater potential to restore JOR maturation to values close to those in normal adults. © 2012 Blackwell Publishing Ltd.

  1. The reinforcing effect of electrical stimulation of the tongue in thirsty rats : brief communication

    NARCIS (Netherlands)

    Slangen, J.L.; Weijmen, J.A.W.M.

    1972-01-01

    Thirsty rats repeatedly closed the electric circuit of a drinkometer with their tongue in the absence of water. The hypothesis that electrical stimulation of the tongue has reinforcing properties was tested. The results indicate that persistent licking by a thirsty rat is dependent on a current as l

  2. Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage

    NARCIS (Netherlands)

    Coppes, RP; Vissink, A; Zeilstra, LJW; Konings, AWT

    1997-01-01

    Purpose: To investigate if muscarinic receptor-stimulated activation of the PLC/PIP2 second messenger pathway prior to irradiation increases the radiotolerance of rat salivary gland. Materials and methods: Rats were treated with pilocarpine, methacholine, reserpine, methacholine plus reserpine, or

  3. Rat pancreatic islet function during prolonged glucose stimulation in vitro : Effect of sex and reproductive state

    NARCIS (Netherlands)

    Moes, H; Koiter, TR

    1997-01-01

    Prolonged stimulation with glucose may induce desensitisation of pancreatic beta-cell function in male rats. The effects of such a treatment on pancreatic islets of pregnant (P) rats, in which beta-cell function is enhanced, were studied in a perifusion design and compared with the effects on islets

  4. Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage

    NARCIS (Netherlands)

    Coppes, RP; Vissink, A; Zeilstra, LJW; Konings, AWT

    1997-01-01

    Purpose: To investigate if muscarinic receptor-stimulated activation of the PLC/PIP2 second messenger pathway prior to irradiation increases the radiotolerance of rat salivary gland. Materials and methods: Rats were treated with pilocarpine, methacholine, reserpine, methacholine plus reserpine, or a

  5. The reinforcing effect of electrical stimulation of the tongue in thirsty rats : brief communication

    NARCIS (Netherlands)

    Slangen, J.L.; Weijmen, J.A.W.M.

    Thirsty rats repeatedly closed the electric circuit of a drinkometer with their tongue in the absence of water. The hypothesis that electrical stimulation of the tongue has reinforcing properties was tested. The results indicate that persistent licking by a thirsty rat is dependent on a current as

  6. Endotoxin-induced liver damage in rats is minimized by β2- adrenoceptor stimulation

    NARCIS (Netherlands)

    Izeboud, C.A.; Hoebe, K.H.N.; Grootendorst, A.F.; Nijmeijer, S.M.; Miert, A.S. van; Witkamp, R.F.; Rodenburg, R.J.T.

    2004-01-01

    Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The

  7. Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats.

    Science.gov (United States)

    Dhall, Sandeep; Silva, João P; Liu, Yan; Hrynyk, Michael; Garcia, Monika; Chan, Alex; Lyubovitsky, Julia; Neufeld, Ronald J; Martins-Green, Manuela

    2015-12-01

    Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischaemia, inflammation and infection costing $7.5 billion/year in the U.S.A. alone, in addition to the morbidity and mortality that occur when the burns are extensive. We previously showed that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization and stimulates angiogenesis. More recently, we developed an alginate sponge dressing (ASD) containing insulin encapsulated in PLGA [poly(D,L-lactic-co-glycolic acid)] microparticles that provides a sustained release of bioactive insulin for >20 days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring healing. Using heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04 mg insulin/cm(2) every 3 days for 9 days have faster closure, a higher rate of disintegration of dead tissue and decreased oxidative stress. In addition, in insulin-treated wounds, the pattern of neutrophil inflammatory response suggests faster clearing of the burned dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibres organized more like a basket weave (normal skin) than aligned and cross-linked (scar tissue). In summary, application of ASD-containing insulin-loaded PLGA particles on burns every 3 days stimulates faster and more regenerative healing. These results suggest insulin as a potential therapeutic agent in burn healing and, because of its long history of safe use in humans, insulin could become one of the treatments of choice when repair and regeneration are critical for proper tissue function.

  8. ARGININE STIMULATED GLUCAGON AND INSULIN-SECRETION BY ISLETS OF LANGERHANS OF PREGNANT AND LACTATING RATS

    NARCIS (Netherlands)

    MOES, H; SCHUILING, GA; KOITER, TR

    Glucagon secretion by isolated pancreatic rat islets was not affected by an increase of the glucose concentration from 2.5 to 5.0 mM, but was stimulated by 25 mM arginine. This stimulation was only slightly increased by pregnancy and lactation. Insulin secretion increased, when the glucose

  9. ARGININE STIMULATED GLUCAGON AND INSULIN-SECRETION BY ISLETS OF LANGERHANS OF PREGNANT AND LACTATING RATS

    NARCIS (Netherlands)

    MOES, H; SCHUILING, GA; KOITER, TR

    1993-01-01

    Glucagon secretion by isolated pancreatic rat islets was not affected by an increase of the glucose concentration from 2.5 to 5.0 mM, but was stimulated by 25 mM arginine. This stimulation was only slightly increased by pregnancy and lactation. Insulin secretion increased, when the glucose concentra

  10. β3-ADRENOCEPTORS INHIBIT STIMULATED NOREPINEPHRINE RELEASE IN SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Torill eBerg

    2014-12-01

    Full Text Available Here, the influence of β3-adrenoceptors on catecholamine release in normotensive and spontaneously hypertensive rats was analysed. Blood pressure was recorded through a femoral artery catheter, and cardiac output by ascending aorta flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total peripheral vascular resistance (TPR was calculated. Norepinephrine release was stimulated with tyramine, which allowed presynaptic release-control to be reflected as changes in the plasma norepinephrine concentration. β3-adrenoceptor agonist (BRL37344 reduced baseline vascular resistance, the tyramine-stimulated norepinephrine overflow and the positive inotropic response to tyramine in hypertensive but not normotensive rats. β3-adrenoceptor antagonist (SR59230A reduced tyramine-stimulated norepinephrine release in both strains and the secretion of epinephrine in hypertensive rats. SR59230A reduced tyramine-induced tachycardia in normotensive rats, and prevented down-regulation of the tyramine-induced rise in resistance in hypertensive rats. It was concluded that the contradicting results obtained by agonist versus antagonist, could be explained by their interaction with two different β-adrenoceptors: The BRL37344-dependent inhibition of stimulated norepinephrine release and positive inotropic response to tyramine was compatible with stimulation of β3-adrenoceptor coupling to inhibitory G-protein. This was observed only in hypertensive rats during stimulated, high levels of circulating catecholamines. The effect of BRL37344 on baseline vascular resistance was compatible with activation of β3-adrenoceptor coupling to endothelial nitric oxide synthase. The inhibitory effect of SR59230A on tyramine-stimulated norepinephrine release in both strains, the increased TPR-response to tyramine in hypertensive rats and tachycardia in normotensive rats may result from inhibition of the low-affinity-state β1-adrenoceptor, also known as the

  11. [Influence of mediopreoptic stimulation on temperature regulation in rats before and after serotonin injection].

    Science.gov (United States)

    Gorynia, I; Bartsch, P

    1975-01-01

    The effects of electrical stimulation of the Area praceoptica medialis (APM) and intraventricular serotonine injection were investigated in thirty Wistar rats tested under normo-, hypo- and hyperthermic conditions. Temperature responses such as oxygen consumption and rectal temperature were measured and heat loss was calculated. The effects of the first stimulation before serotonine injection were compared with those of the second one after serotonine application in order to prove the influence of serotonine on temperature responses due to APM stimulation. On the other hand, the influence of stimulation on changes produced by serotonine injection should be shown by the recordings of the second serotonine responses with stimulation effects and by comparison of these with those of the first serotonine responses without stimulation effects. The first APM stimulation depending on the rectal temperature before stimulation resulted in decreasing oxygen consumption in hypothermic rats while increasing that of hyperthermic animals. There was a little decrease of rectal temperature under hyper- and normothermic conditions. while under hypothermic conditions animals showed marked depression. The increase in heat loss, however, was least in hyperthermic rats and most pronounced in hypothermic animals. The second APM stimulation did almost not affect the temperature responses after serotonine application in normothermic rats, while causing supercooling agin under hypothermic conditions and insignificant cooling at hyperthermic environment temperature. Comparison of the first and second stimulation effects revealed statistical significant differences at normo-, hypo- and hyperthermic temperatures. The results are discussed under consideration of the different starting conditions before the first and second stimulation. These findings do not indicate that serotonine would shift the sensibility of mediopraeoptic structures and thus unequivocally modifies stimulation effects.

  12. Vaccenic and elaidic acid modify plasma and splenocyte membrane phospholipids and mitogen-stimulated cytokine production in obese insulin resistant JCR: LA-cp rats.

    Science.gov (United States)

    Ruth, Megan R; Wang, Ye; Yu, Howe-Ming; Goruk, Susan; Reaney, Martin J; Proctor, Spencer D; Vine, Donna F; Field, Catherine J

    2010-02-01

    This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

  13. Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    LIU Huan-guang; YANG An-chao; MENG Da-wei; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures.In this study,we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.Methods Three groups of rats were used:(1) a stimulation group (n=12),(2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA),and (3) a control group (n=12) with sham surgery.Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT.High-frequency stimulation was performed in each group except the sham stimulation group.Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in thestimulation group.The concentrations of glucose,lactate,and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.Results The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020,P=0.001; respectively).However,no significant difference in the concentration of glucose and pyruvate was found between these groups (P>0.05).Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05),but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).Conclusions This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation.These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

  14. Antihyperglycemic and antihyperlipidemic activity of plectranthus amboinicus on normal and alloxan-induced diabetic rats.

    Science.gov (United States)

    Viswanathaswamy, A H M; Koti, B C; Gore, Aparna; Thippeswamy, A H M; Kulkarni, R V

    2011-03-01

    The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

  15. Insulin inhibits glucagon-induced glycogenolysis normally in perivenous hepatocytes of Wistar fatty rats.

    Science.gov (United States)

    Ikezawa, Yoshihiro; Yamatani, Keiichi; Ohnuma, Hiroshi; Daimon, Makoto; Manaka, Hideo; Sasaki, Hideo

    2005-08-01

    Wistar fatty (WF) rats are obese, hyperinsulinemic and hyperglycemic, and thus a model of type 2 diabetes mellitus. Since we have found that insulin specifically inhibits glucagon-induced glycogenolysis in perivenous hepatocytes (PVH) from normal rats, we examined the inhibitory effect of insulin on glucagon-induced glycogenolysis in PVH of hyperinsulinemic WF rats. Basal glucose release was 64.0+/-4.1 nmol/mgprotein/30 min from PVH of lean littermates (WL rats) and 137.0+/-19.3 nmol/mgprotein/30 min from that of WF rats (pglycogenolysis in PVH similarly between WL and WF rats, to 56.7+/-13.3% and to 46.1+/-7.5%, respectively. Thus, the antagonizing effect of insulin on glucagon-induced increase in glycogenolysis was preserved in PVH of hyperinsulinemic and hyperglycemic WF rats.

  16. Modulation by thyroid hormones of rat parotid amylase secretion stimulated by 5-hydroxytryptamine.

    Science.gov (United States)

    Ostuni, Mariano Aníbal; Houssay, Alberto Bernardo; Tumilasci, Omar René

    2003-12-01

    The effects of 5-hydroxytryptamine (5-HT) upon amylase secretion by rat parotid glands were studied in three groups of animals: (a) intact control rats (euthyroid rats); (b) hypothyroid rats obtained by surgical thyroidectomy 2 wk before the experiments; and (c) hyperthyroid rats obtained by the administration of sodium l-triiodothyronine for 2 wk before the experiments. Hyperthyroid rats showed significantly higher baseline amylase release than control rats. When the glands were stimulated with 5-HT (30 micro m), amylase release was significantly lower in the hypothyroid group and higher in the hyperthyroid rats than in control group. Addition of cholinergic, adrenergic or substance P antagonists did not modify 5-HT-stimulated amylase activity. The effects of 5-HT were partly but significantly blocked by the addition of 10 micro m methysergide (HT1/2/7 receptor blocker) in the three groups of rats. In contrast, 10 micro m ketanserine (HT2A receptor blocker) partly blocked the response to 5-HT only in the hyperthyroid animals. It was concluded that 5-HT induces amylase secretion by rat parotid glands through specific serotoninergic receptors, and that thyroid status modulates the 5-HT effect.

  17. Beta-adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure.

    Science.gov (United States)

    Maron, Michael B; Luther, Daniel J; Pilati, Charles F; Ohanyan, Vahagn; Li, Tianbo; Koshy, Shyny; Horne, Walter I; Meszaros, J Gary; Walro, Jon M; Folkesson, Hans G

    2009-09-01

    The alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure.

  18. Synthesis, characterization and evaluation of bone targeting salmon calcitonin analogs in normal and osteoporotic rats.

    Science.gov (United States)

    Bhandari, Krishna Hari; Newa, Madhuri; Chapman, Jillian; Doschak, Michael R

    2012-02-28

    In order to assess the therapeutic efficacy of an antiresorptive drug with imparted bone targeting potential using bisphosphonate (BP) conjugation and an improved pharmacokinetic profile using PEGylation, we synthesized, characterized and evaluated in vivo efficacy of bone-targeting PEGylated salmon calcitonin (sCT) analog (sCT-PEG-BP). sCT-PEG-BP was compared with non-PEGylated bone targeting sCT analog (sCT-BP) and unmodified, commercially available sCT. sCT-PEG-BP conjugates were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis. The effect of PEG-BP or BP upon sCT secondary structure was examined by Circular Dichroism and sCT-PEG-BP was evaluated for in vitro bone mineral Hydroxyapatite (HA) binding ability and calcium salts specificity using a binding assay for bone HA and several calcium salts. Anti-calcitonin antibody binding ability of these analogs was determined using enzyme-linked immunosorbent assay (ELISA), by reacting bone targeting sCT analogs with calcium phosphate coated Osteologic® plates and detecting the bound sCT using anti-sCT antibody. Potential cytotoxicity of these compounds was evaluated in monocytic RAW 264.7 cells, and sCT bioactivity was evaluated using an in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. Finally, in vivo efficacy of each compound was evaluated by determining the plasma levels of calcium after s.c. administration in normal rats, and in a rat model of Osteoporosis, secondary to ovariectomy (OVX). In vivo micro-computed tomography (micro-CT) was used to temporally map and quantify alterations in bone volume and bone mineral density (BMD) in the same animals at 1, 4, 8 and 12 weeks after OVX surgery. Sixteen 6 week old virgin female rats underwent OVX surgery followed by the daily s.c. injection of 2.5IU/kg/day sCT or equivalent analogs, and compared to four sham-operated, placebo treated control rats. Our results showed the chemical coupling of

  19. Expression of PirB in Normal and Injured Spinal Cord of Rats

    Institute of Scientific and Technical Information of China (English)

    周迎春; 迁荣军; 饶竞; 翁密霞; 易序霞

    2010-01-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expre...

  20. Stimulation of colonic mucosal growth associated with oxidized redox status in rats.

    Science.gov (United States)

    Tian, Junqiang; Washizawa, Naohiro; Gu, Li H; Levin, Marc S; Wang, Lihua; Rubin, Deborah C; Mwangi, Simon; Srinivasan, Shanthi; Gao, Yuhao; Jones, Dean P; Ziegler, Thomas R

    2007-03-01

    Limited data in animal models suggest that colonic mucosa undergoes adaptive growth following massive small bowel resection (SBR). In vitro data suggest that intestinal cell growth is regulated by reactive oxygen species and redox couples [e.g., glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) redox]. We investigated the effects of SBR and alterations in redox on colonic growth indexes in rats after either small bowel transection (TX) or 80% midjejunoileal resection (RX). Rats were pair fed +/- blockade of endogenous GSH synthesis with buthionine sulfoximine (BSO). Indexes of colonic growth, proliferation, and apoptosis and GSH/GSSG and Cys/CySS redox potentials (E(h)) were determined. RX significantly increased colonic crypt depth, number of cells per crypt, and epithelial cell proliferation [crypt cell bromodeoxyuridine (BrdU) incorporation]. Administration of BSO markedly decreased colonic mucosal GSH, GSSG, and Cys concentrations in both TX and RX groups, with a resultant oxidation of GSH/GSSG and Cys/CySS E(h). BSO did not alter colonic crypt cell apoptosis but significantly increased all colonic mucosal growth indexes (crypt depth, cells/crypt, and BrdU incorporation) in both TX and RX groups in a time- and dose-dependent manner. BSO significantly decreased plasma GSH and GSSG, oxidized GSH/GSSG E(h), and increased plasma Cys and CySS concentrations. Collectively, these data provide in vivo evidence indicating that oxidized colonic mucosal redox status stimulates colonic mucosal growth in rats. The data also suggest that GSH is required to maintain normal colonic and plasma Cys/CySS homeostasis in these animal models.

  1. Rats with Chronic, Stable Pulmonary Hypertension Tolerate Low Dose Sevoflurane Inhalation as Well as Normal Rats Do.

    Directory of Open Access Journals (Sweden)

    Xiaoqing Yin

    Full Text Available The effects of low concentration of sevoflurane on right ventricular (RV function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH.Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings. The protein levels of SERCA2, PLB and p-PLB expression was analyzed by western blot to assess their relevance in PAH.Rats with PAH presented with RV hypertrophy and increased pulmonary arterial pressure. The values of Ea, R/L ratio, ESP, SW, PRSW, +dP/dtmax and the slope of the dP/dtmax-EDV relationship increased significantly in PAH rats (P<0.05. Sevoflurane induced a concentration-dependent decrease of systemic and pulmonary blood pressure, HR, RV contractility, and increased the R/L ratio in both groups. Sevoflurane reduced the expression of SERCA2 and increased the expression of PLB in both groups. Interestingly, sevoflurane only reduced the p-PLB/PLB ratio in PAH rats, not in normal rats.Rats with chronic, stable pulmonary hypertension tolerate low concentrations of sevoflurane inhalation as well as normal rats do. It may be related to the modulation of the SERCA2-PLB signaling pathway.

  2. Inhibitory Effect and Possible Mechanism of Intraurethral Stimulation on Overactive Bladder in Female Rats.

    Science.gov (United States)

    Tian, Yu; Liao, Limin; Wyndaele, Jean Jacques

    2015-09-01

    To investigate the inhibitory effect and possible mechanism of intraurethral stimulation on overactive bladder (OAB) induced by acetic acid irritation. Cystometry was performed in 13 urethane-anesthetized female rats. Intravesical infusion of 0.5% acetic acid was used to irritate the bladder and induce OAB. Multiple cystometrograms were performed with mirabegron, continuous stimulation, mirabegron plus continuous stimulation, and β3-adrenoceptor antagonist plus continuous stimulation to determine the mechanism underlying the inhibitory effect by intraurethral stimulation. Infusion of acetic acid significantly decreased bladder capacity. Intraurethral stimulation at 2.5 Hz plus mirabegron significantly increased bladder capacity and decreased the nonvoiding contraction count. The changes were strongly inhibited after the β3-adrenoceptor antagonist was administered. Activation of urethral afferent nerves can reverse OAB, which activates C-fiber afferent nerves. This animal study indicates that intraurethral stimulation may interfere with OAB through hypogastric nerve activation and pudendal nerve neuromodulation.

  3. Functional and histologic changes after repeated transcranial direct current stimulation in rat stroke model.

    Science.gov (United States)

    Kim, Sang Jun; Kim, Byeong Kwon; Ko, Young Jin; Bang, Moon Suk; Kim, Man Ho; Han, Tai Ryoon

    2010-10-01

    Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.

  4. Hypoglycemic effect of aqueous extract of Ammi visnaga in normal and streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Jouad, Hassan; Maghrani, Mhamed; Eddouks, Mohammed

    2002-01-01

    The effect of the aqueous extract of Ammi visnaga (Apiaceae) on blood glucose levels was investigated in fasting normal and streptozotocin-induced diabetic rats after single and repeated oral administration. The aqueous extract of Ammi visnaga (AV) at a dose of 20 mg/kg significantly reduced blood glucose in normal rats six hours after a single oral administration (P < 0.005) and nine days after repeated oral administration (P < 0.05). This hypoglycemic effect is more pronounced in streptozotocin (STZ) diabetic rats (P < 0.001). Acute toxicity (LD50) and general behavioural effects of an aqueous extract of AV fruits was studied in mice. The LD50 of intraperitoneal (i.p.) and oral administration was 3.6 and 10.1 g/kg, respectively. These findings suggest that the aqueous extract of AV possess significant hypoglycemic effect in both normal and STZ diabetic rats and support, therefore, its claimed clinical use by the Moroccan population.

  5. Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Gribble, Fiona M; Hartmann, Bolette

    2014-01-01

    glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose...... was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might...... be useful targets for type 2 diabetes mellitus and obesity drug development....

  6. Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary

    Directory of Open Access Journals (Sweden)

    Gao Li-Zhi

    2009-12-01

    Full Text Available Abstract Background A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release. Methods The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined. Results The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent. Conclusions The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.

  7. A preparation for studying electrical stimulation of the retina in vivo in rat.

    Science.gov (United States)

    Baig-Silva, M S; Hathcock, C D; Hetling, J R

    2005-03-01

    A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

  8. Lipid Profile and Antioxidant Enzymes in Normal and Stressed Rat Fed with Palm Olein

    Directory of Open Access Journals (Sweden)

    Eqbal M.A. Dauqan

    2012-01-01

    Full Text Available Problem statement: The objective of the study was to evaluate the effect of Red Palm Olein (RPO and Palm Olein (PO on lipid profile and antioxidant enzyme in normal and stressed rat. Approach: Thirty six Sprague Dawley male rats which were randomly divided into six groups of 6 rats per group (tree normal groups and three stressed groups were treated with 15% of RPO and PO for four weeks. Results: The results at 4 weeks of treatment showed a decline in Low Density Lipoprotein Cholesterol (LDL-C level at RPO and PO for normal and stressed groups compared to the control group. The High Density Lipoprotein Cholesterol (HDL-C level increased in RPO and PO of the normal and stressed groups. There was significant decreased (p≤0.05 in the TC in RPO normal group for 4 weeks of treatment compared to the control group while the TC in PO was within the normal range and increased in stressed group. After 4 weeks of treatment the study indicated that there was no significant (p≥0.05 effect on antioxidant enzyme (superoxide dismutase in stressed rat liver but there was a significant decreased (p≤0.05 on catalase in stressed rat liver. Conclusion: These results could be due to the high content of vitamin E (tocopherols and tocotrienols and β-carotene in red palm olein.

  9. Transcranial Direct-Current Stimulation Increases Extracellular Dopamine Levels in the Rat Striatum

    Directory of Open Access Journals (Sweden)

    Tomoko eTanaka

    2013-04-01

    Full Text Available Background: Transcranial direct-current stimulation is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo. Objective/Hypothesis: To investigate whether the application of cathodal or anodal transcranial direct-current stimulation affects extracellular dopamine and serotonin levels in the rat striatum. Methods: Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal transcranial direct-current stimulation was applied continuously for 10 min with a current intensity of 800 µA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation.Results: Following the application of cathodal, but not anodal, transcranial direct-current stimulation for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels. Conclusion: These findings suggest that transcranial direct-current stimulation has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia.

  10. Nucleus accumbens deep brain stimulation in a rat model of binge eating.

    Science.gov (United States)

    Doucette, W T; Khokhar, J Y; Green, A I

    2015-12-15

    Binge eating (BE) is a difficult-to-treat behavior with high relapse rates, thus complicating several disorders including obesity. In this study, we tested the effects of high-frequency deep brain stimulation (DBS) in a rodent model of BE. We hypothesized that BE rats receiving high-frequency DBS in the nucleus accumbens (NAc) core would have reduced binge sizes compared with sham stimulation in both a 'chronic BE' model as well as in a 'relapse to chronic BE' model. Male Sprague-Dawley rats (N=18) were implanted with stimulating electrodes in bilateral NAc core, and they received either active stimulation (N=12) or sham stimulation (N=6) for the initial chronic BE experiments. After testing in the chronic BE state, rats did not engage in binge sessions for 1 month, and then resumed binge sessions (relapse to chronic BE) with active or sham stimulation (N=5-7 per group). A significant effect of intervention group was observed on binge size in the chronic BE state, but no significant difference between intervention groups was observed in the relapse to chronic BE experiments. This research, making use of both a chronic BE model as well as a relapse to chronic BE model, provides data supporting the hypothesis that DBS of the NAc core can decrease BE. Further research will be needed to learn how to increase the effect size and decrease deep brain stimulation-treatment outcome variability across the continuum of BE behavior.

  11. Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

    Science.gov (United States)

    Sathya, S; Kokilavani, R; Gurusamy, K

    2008-10-01

    The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

  12. Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats.

    Science.gov (United States)

    Guan, Yun; Wacnik, Paul W; Yang, Fei; Carteret, Alene F; Chung, Chih-Yang; Meyer, Richard A; Raja, Srinivasa N

    2010-12-01

    The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear. We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The conditioning stimulation intensity was set at the lowest current that evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ- or C-compound action potential. Within 15 min of the dorsal column or root conditioning stimulation, the spontaneous activity rate of WDR neurons was significantly reduced in nerve-injured rats. Conditioning stimulation also significantly attenuated WDR neuronal responses to mechanical stimuli in nerve-injured rats and inhibited the C-component of the neuronal response to graded intracutaneous electrical stimuli applied to the receptive field in nerve-injured and sham-operated rats. It is noteworthy that dorsal column stimulation blocked windup of WDR neuronal response to repetitive intracutaneous electrical stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root stimulation inhibited windup only in sham-operated rats. Therefore, stimulation of putative spinal substrates at A-fiber intensities with parameters similar to those used by patients with spinal cord stimulators attenuated established WDR neuronal hyperexcitability in the neuropathic condition and counteracted activity-dependent increase in neuronal excitability (i.e., windup). These results suggest a potential cellular mechanism underlying spinal cord stimulation-induced pain relief. This in vivo model allows the neurophysiologic basis for spinal cord stimulation-induced analgesia to be studied.

  13. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    Science.gov (United States)

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

  14. Glucose production and storage in hepatocytes isolated from normal versus diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Olivieri, M.C.; Dragland-Meserve, C.J.; Parker Botelho, L.H.

    1987-05-01

    The rates of glucose production and storage were compared in hepatocytes isolated from normal versus insulin-resistant diabetic rats. A single low-dose (40 mg/kg) IV injection of streptozotocin to 250 g rats resulted in a Type II diabetic animal model which was hyperglycemic with normal insulin levels. Addition of 8 mM /sup 14/C-lactate and 2 mM pyruvate to hepatocytes resulted in a linear increase in total glucose production (/sup 14/C-glucose and unlabeled glucose) and incorporation into glycogen measured over 120 min. The rate of gluconeogenesis was estimated from the production of /sup 14/C-glucose and the rate of glycogenolysis was estimated from the production of unlabeled glucose in cells incubated in the presence or absence of /sup 14/C-labelled substrate. There was not significant difference in total glucose production in hepatocytes isolated from normal versus diabetic rats, however, the contribution from gluconeogenesis versus glycogenolysis was significantly different. Following a 1 h incubation of cells from normal rats, 42% of the total glucose production was due to gluconeogenesis and 58% was due to glycogenolysis. In cells from diabetic rats, 83% of total glucose production was from gluconeogenesis and 17% from glycogenolysis. Also, incubation with /sup 14/C-lactate/pyruvate resulted in a 3.3-fold increase in /sup 14/C-glucose incorporation into glycogen in hepatocytes isolated from normal rats compared to diabetic rats. These data suggest that alterations occur in the rate-limiting enzymes responsible for glucose production and storage in hepatocytes isolated from a rat model of insulin-resistant Type II diabetes.

  15. Studies on Renin Stimulation in Normal Controls and in Patients with Essential Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Chang Soon; Choe, Kang Won; Lee, Hong Kyu; Lee, Jung Sang [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1978-03-15

    To find out a convenient and reliable method of detecting low renin status, we employed intravenous furosemide injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from 2.5+-1.95 ng/ml/hr (basal) to 4.5+-2.51, 5.2+-2.49 and 4.2+-2.44 ng/ml/hr at 1, 2 and 3 hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3 hrs gave rise to considerable increase in PRA (4.0+-2.92 from 2.4+-1.85), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole (2.9+-2.75). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hyporesponders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients (52.9+-5.38 years old) was significantly higher than that of high and normal renin patients (44.1+-13.78 years old).

  16. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Quantitative real-time polymerase chain reaction (qPCR) has become a widely used tool in the search for disease genes. When examining gene expression with qPCR in psychiatric diseases, endogenous reference gene(s) must be used for normalization. Traditionally, genes such as beta-actin (ActB), Gap...

  17. Low-frequency stimulation of the kindling focus delays basolateral amygdala kindling in immature rats.

    Science.gov (United States)

    Velísek, Libor; Velísková, Jana; Stanton, Patric K

    2002-06-21

    Stimulation of deep brain sites is a new approach for treatment of intractable seizures. In adult rats, low-frequency stimulation (LFS; 1-3 Hz) of the kindling site interferes with the course of kindling epileptogenesis. In this study we determined whether the LFS will be effective against the fast kindling in the basolateral amygdala in immature, 15 day old rats. LFS (15 min of 1 Hz stimulation) was applied after each of the 1 s, 60 Hz kindling stimulus. LFS suppressed afterdischarge duration and seizure stage throughout the course of kindling, which indicates a strong antiepileptogenic potential. As the kindling and LFS stimulation patterns are similar to those used for induction of long-term potentiation and long-term depression (LTD), respectively, LTD or depotentiation may play a role in the mechanism of action.

  18. Slow And Fast Kindling During Hyperthermic Stimulation In Rats : Implications For Hot Water Epilepsy

    Directory of Open Access Journals (Sweden)

    Krishnamurthy U

    2000-01-01

    Full Text Available Hot water epilepsy, a reflex epilepsy precipitated by hot water stimulation, has been commonly reported from southern India. Clinical studies have indicated that a phenomenon of hyperthermic kindling may underlie the appearance of spontaneous seizures in some hot water epilepsy patients at a later stage. Our present experiments with a rat model for hot water epilepsy demonstrate the occurrence of slow and fast kindling during hyperthermic seizures, induced by repeated stimulations with hot water, in different populations of rats. These findings have important implications for the pathophysiology and management of this epileptic syndrome in human beings.

  19. Response threshold to aversive stimuli in stimulated early protein-malnourished rats

    Directory of Open Access Journals (Sweden)

    L.F. Rocinholi

    1997-03-01

    Full Text Available Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition

  20. Pulse electrical arc stimulator based on single-electrode for active exercise in tail-suspension rat

    Institute of Scientific and Technical Information of China (English)

    孙联文; 谢添; 樊瑜波; 张晓薇; 孙瑶; 杨肖

    2008-01-01

    To make rat do active exercise to counteract bone loss in the rat tail-suspension model, a pulse electrical stimulator based on single-electrode with a low-current and a high-voltage was designed. The stimulator was controlled by SCM (single chip micyoco) that could accurately control the stimulation duration and the interval between stimulations, and cease the operation after the recorded number of stimulation had reached the value set by the program. With the help of posture estimation part, the device would operate intelligently by determining whether to stimulate or not, depending on the posture of rat’s limb. Software was developed to make operator control the stimulator using computer, save the experiment data and print the report. In practical experiment, the voltaic arc is generated by the stimulator, and impacted on the rat’s thenar. This induced pain to the rat and the rat would actively contract its hindlimb to evade the pain, so active exercise was carried out. The tail-suspension rats were trained twice every day for 14 d. At the 0 and 14th day, bone mineral density of rat femurs was determined by dual energy X-ray absorptiometry (DXA). The results show that the active exercise stimulated by the pulse electrical arc stimulator can attenuate weightlessness-induced bone loss, and this device is a convenient steady performance electrical stimulator that can surely induce rat’s hindlimb to do active exercise.

  1. Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats.

    Science.gov (United States)

    de La Fuente, Raquel N; Rodrigues, Bruno; Moraes-Silva, Ivana C; Souza, Leandro E; Sirvente, Raquel; Mostarda, Cristiano; De Angelis, Kátia; Soares, Pedro P; Lacchini, Silvia; Consolim-Colombo, Fernanda; Irigoyen, Maria-Cláudia

    2013-09-01

    In the present study we evaluated the effects of short-term pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats. Male Wistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine-treated groups. Pyridostigmine was administered in the drinking water, starting immediately after MI or sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly by LV catheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment. Pyridostigmine prevented the impairment of +dP/dT and reduced the MI area in infarcted + pyridostigmine compared with infarcted rats (7 ± 3% vs 17 ± 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 ± 3 vs 94 ± 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 ± 0.2 vs 2.5 ± 0.2 b.p.m./mmHg, respectively) and bradycardic (-0.42 ± 0.01 vs -1.9 ± 0.1 b.p.m./mmHg) responses, and reduced the low frequency/high frequency ratio of HRV (0.81 ± 0.11 vs 0.24 ± 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats. In conclusion, the data suggest that short-term pyridostigmine treatment started early after MI can improve BRS, HRV and parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance after MI.

  2. State-dependent amygdala stimulation-induced cardiovascular effects in rats.

    Science.gov (United States)

    Chiou, Ruei-Jen; Kuo, Chung-Chih; Liang, Keng-Chen; Yen, Chen-Tung

    2009-12-31

    Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.

  3. Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

    Science.gov (United States)

    Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

    2016-12-01

    This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

  4. [The adrenergic innervation of the normal rat uterus and during pregnancy].

    Science.gov (United States)

    Rakitskaia, V V; Chudinov, Iu V; Shaliapina, V G

    1990-09-01

    Histochemical analysis revealed that, normally, the main amount of adrenergic fibers in the rat uterus is connected with vascular innervation. The amount of neural elements projecting to the muscle cells in insignificant. In pregnancy, the amount of fibers with the specific fluorescence decreases and they completely disappear from the myometrium in parturient rats. Biochemical analysis corroborated the finding that the noradrenaline level is considerably decreased at the time in sympathetic neurons innervating the uterus thus leading to a physiological "desympathization" of the organ.

  5. Effects of pharmacological serum from normal and liver fibrotic rats on HSCs

    Institute of Scientific and Technical Information of China (English)

    Xi-Xian Yao; Tao Lv

    2005-01-01

    AIM: To make drug sera of Salvia miltiorrhiza and Yigankang, both of which are Chinese herbs that activate bleeding and eliminate stasis, in normal rats and those with liver fibrosis, respectively. To investigate and compare the effects of the two different drug sera on the proliferation and activation of hepatic stellate cells (HSCs).METHODS: Some rats were induced with liver fibrosis:40% carbon tetrachloride (CCl4) subcutaneous injection,twice a week for 9 wk. Salvia miltiorrhiza, Yigankang,colchicines and normal saline were administered into the stomachs of normal rats and those with liver fibrosis.Drug sera were extracted 5 d later. HSCs in vitro were cultivated in different drug sera for 24 h. The rates of proliferation and expression of α-smooth muscle actin (α-SMA) were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry stain, respectively.RESULTS: The drug sera from normal and liver fibrotic rats could be used to cultivate HSCs and to observe the effects of the corresponding components of herbs on HSCs. Salvia miltiorrhiza and Yigankang had better inhibitory effects on HSCs than colchicines (MTT: normal drug serum: Salvia miltiorrhiza 0.42±0.08, Yigankang 0.32±0.10 vs colchicines 0.45±0.12 pathological drug serum: Salvia miltiorrhiza 0.33±0.02, Yigankang 0.26±0.01vs colchicines 0.41±0.09. P<0.05). The drug sera of Salvia miltiorrhiza, Yigankang from liver fibrotic rats had a stronger inhibitory effect than the same ones from normal rats (MTT: Salvia miltiorrhiza: normal drug serum 0.42±0.08 vs pathological drug serum 0.33±0.02. Yigankang: normal drug serum 0.32±0.10 vs pathological drug serum 0.26±0.01.P<0.05).CONCLUSION: Salvia miltiorrhiza and Yigankang could inhibit the expression of α-SMA and the proliferation of HSCs. The drug sera from normal and liver fibrotic rats had different effects on HSCs, probably due to different metabolic processes, effective components and different

  6. Antihyperglycemic and antihyperlipidemic activity of Plectranthus amboinicus on normal and alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    A. H. M. Viswanathaswamy

    2011-01-01

    Full Text Available The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg. Normal as well as diabetic rats were divided into groups (n=6 receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

  7. Apple cider vinegar attenuates lipid profile in normal and diabetic rats.

    Science.gov (United States)

    Shishehbor, F; Mansoori, A; Sarkaki, A R; Jalali, M T; Latifi, S M

    2008-12-01

    In this study, the effect of apple cider vinegar on Fasting Blood Glucose (FBG), glycated haemoglobin (HbA1c) and lipid profile in normal and diabetic rats was investigated. Diabetes was induced in male Wistar rats (300+/-30 g) by the intraperitoneal injection of streptozotocin (60 mg kg(-1) of body weight). Both normal and diabetic animals were fed with standard animal food containing apple cider vinegar (6% w/w) for 4 weeks. Fasting blood glucose did not change, while HbA1c significantly decreased by apple cider vinegar in diabetic group (pvinegar, significant reduction of low density lipoprotein-cholesterol (LDL-c) (pcider vinegar also reduced serum triglyceride (TG) levels (pcider vinegar improved the serum lipid profile in normal and diabetic rats by decreasing serum TG, LDL-c and increasing serum HDL-c and may be of great value in managing the diabetic complications.

  8. Acute hypotensive and diuretic activities of Artemisia herba alba aqueous extract in normal rats

    Institute of Scientific and Technical Information of China (English)

    Naoufel Ali Zeggwagh; Jean Baptiste Michel; Mohamed Eddouks

    2014-01-01

    Objective:To evaluate the effect of Artemisia herba alba (A. herba alba) intravenous injection on cardiovascular and renal function in normal rats. Methods:The effect of intravenous injection of A. herba alba extract at the different doses of 50, 100 and 200 mg/kg was investigated in normal rats. Diuresis, heart frequency and electrolytes concentrations were analyzed. Results: Intravenous bolus injection of A. herba alba at the different doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure (P Conclusions: We conclude that the aqueous A. herba alba extract possesses a potent acute hypotensive effect on normal rats. In addition, A. herba alba perfusion may affect renal function to increase urine and electrolytes excretion.

  9. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

    Directory of Open Access Journals (Sweden)

    Qinna NA

    2015-05-01

    Full Text Available Nidal A Qinna,1 Adnan A Badwan2 1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, 2Research and Innovation Centre, The Jordanian Pharmaceutical Manufacturing Co. Plc. (JPM, Amman, Jordan Abstract: Streptozotocin (STZ is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL, noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were

  10. Does ultrasound stimulate osteoconduction? A placebo-controlled single-blind study using collagen membranes in the rat mandible

    NARCIS (Netherlands)

    Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B; de Bont, LGM

    2005-01-01

    Purpose: To investigate whether ultrasound can stimulate osteoconduction in the mandible, an attempt was made to stimulate the osteoconductive process with low-intensity pulsed ultrasound in rats. Materials and Methods: In 64 rats, a 5.0-mm diameter circular mandibular defect was made in the ramus a

  11. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine.

    Science.gov (United States)

    Kuhre, Rune E; Frost, Charlotte R; Svendsen, Berit; Holst, Jens J

    2015-02-01

    Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w/v) stimulated the secretion dose dependently, but vascular glucose was without significant effect at 5, 10, 15, and 25 mmol/L. GLP-1 stimulation by luminal glucose (20%) secretion was blocked by the voltage-gated Ca channel inhibitor, nifedipine, or by hyperpolarization with diazoxide. Luminal administration (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-D-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations. Glucose transported by GLUT2 may act after metabolization, closing KATP channels similar to sulfonylureas, which also stimulated secretion. Our data indicate that SGLT1 activity is the driving force for glucose-stimulated GLP-1 secretion and that KATP-channel closure is required to stimulate a full-blown glucose-induced response.

  12. Furosemide stimulates macula densa cyclooxygenase-2 expression in rats

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    ascending limb of Henle (cTALH) cells, and is inversely regulated by dietary salt intake. This study aimed to elucidate whether the effect of NaCl on macula densa COX-2 expression is mediated by transepithelial transport of NaCl. METHODS: To this end, male Sprague-Dawley rats received subcutaneous infusions...

  13. A comparison of adrenergic receptors of rat ascites hepatoma AH130 cells with those of normal rat hepatocytes.

    Science.gov (United States)

    Sanae, F; Miyamoto, K; Koshiura, R

    1988-04-01

    The pharmacological specificity of adrenergic receptors in the plasma membrane of rat ascites hepatoma AH130 cells was compared with that in normal rat hepatocytes. The number of [125I]iodocyanopindolol-binding sites was much greater in AH130 cells than in the hepatocytes. We characterized the alpha-adrenergic receptor subtypes using the alpha 1-selective ligand [3H]prazosin and the alpha 2-selective ligand [3H]clonidine. AH130 cells had fewer prazosin-binding sites than the hepatocytes and about 8 times as many clonidine-binding sites of high affinity. The results showed that the adrenergic receptors in AH130 cells have pharmacological properties that are very different from those of the receptors in normal rat hepatocytes.

  14. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    Science.gov (United States)

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Ovarian response in consecutive cycles of ovarian stimulation in normally ovulating women.

    Science.gov (United States)

    Ahmed Ebbiary, N A; Morgan, C; Martin, K; Afnan, M; Newton, J R

    1995-03-01

    Ovarian stimulation combined with intra-uterine insemination (IUI) is an effective treatment of non-tubal infertility but most women undergo several cycles of treatment to achieve a pregnancy. This prospective study was designed to assess the consistency (or variation) of ovarian responses and the effect of various ovarian stimulation protocols on this consistency in consecutive cycles of ovarian stimulation and IUI in women with non-ovulatory infertility. A total of 86 regularly menstruating ovulating patients each completed three to six cycles of ovarian stimulation and IUI (n = 347 cycles). Ovarian stimulation was achieved by sequential clomiphene citrate/human menopausal gonadotrophin (HMG), HMG-only or combined gonadotrophin-releasing hormone analogue--HMG protocols in 33, 29 and 24 patients respectively, and each patient used the same protocol consistently throughout the study. Standard methods were used to monitor ovarian response and to perform IUI. Using each patient as her own control, repeated measurements analysis of variance revealed consistency of ovarian response in consecutive ovarian stimulation cycles, as shown by the number and mean diameter of maturing pre-ovulatory follicles, peak plasma oestradiol, duration of stimulation and mean HMG requirements. This consistency existed using any of the ovarian stimulation protocols. We conclude that regularly menstruating and ovulating women are likely to have similar ovarian responses in consecutive cycles of ovarian stimulation and IUI if the same ovarian stimulation protocol is used consistently.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

    Directory of Open Access Journals (Sweden)

    Heidi N. Bagley

    2013-01-01

    Full Text Available Intrauterine growth restriction (IUGR predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2 in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA, a PPARγ agonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI- induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1 normalizes IUGR-induced changes in adipose deposition and visceral PPARγ expression in male rats and (2 increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

  17. Unilateral neuromodulation of the ventromedial hypothalamus of the rat through deep brain stimulation

    Science.gov (United States)

    Lehmkuhle, M. J.; Mayes, S. M.; Kipke, D. R.

    2010-06-01

    This study offers evidence that long-term deep brain stimulation of the ventromedial hypothalamus (VMH) can alter weight gain in mammals without affecting feeding behavior. Animals stimulated unilaterally at high frequencies of 150 or 500 Hz demonstrated increased CO2 production that decreased from prestimulation levels after the stimulation was removed. Animals stimulated for up to 6 weeks gained weight at a lower rate than normal animals or animals implanted with an electrode but not stimulated. Stimulated animals exhibited normal food and water consumption. A significant decrease in efficiency was observed during stimulation that coincided with an increase in the amount of feces produced. Whereas the weight of control animals was significantly different from week to week, the weight of stimulated animals did not change accordingly. These data suggest that the VMH may be a viable target for long-term deep brain stimulation for modulation of the neural mechanisms of metabolism. The potential therapeutic effects of deep brain stimulation of the hypothalamus are discussed.

  18. The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension

    Directory of Open Access Journals (Sweden)

    T.A. Uggere

    2000-05-01

    Full Text Available Cardiopulmonary reflexes are activated via changes in cardiac filling pressure (volume-sensitive reflex and chemical stimulation (chemosensitive reflex. The sensitivity of the cardiopulmonary reflexes to these stimuli is impaired in the spontaneously hypertensive rat (SHR and other models of hypertension and is thought to be associated with cardiac hypertrophy. The present study investigated whether the sensitivity of the cardiopulmonary reflexes in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. Untreated SHR and WKY rats were fed a normal diet. Another groups of rats were treated with enalapril (10 mg kg-1 day-1, mixed in the diet; SHRE or WKYE for one month. After treatment, the volume-sensitive reflex was evaluated in each group by determining the decrease in magnitude of the efferent renal sympathetic nerve activity (RSNA produced by acute isotonic saline volume expansion. Chemoreflex sensitivity was evaluated by examining the bradycardia response elicited by phenyldiguanide administration. Cardiac hypertrophy was determined from the left ventricular/body weight (LV/BW ratio. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR as compared to WKY rats. As compared to the levels observed in normotensive WKY rats, however, enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE. SHR with established hypertension had a higher LV/BW ratio (45% as compared to normotensive WKY rats. With enalapril treatment, the LV/BW ratio was reduced to 19% in SHRE. Finally, the reflex-induced bradycardia response produced by phenyldiguanide was significantly attenuated in SHR compared to WKY rats. Unlike the effects on the volume reflex, the sensitivity of the cardiac chemosensitive reflex to phenyldiguanide was not restored by enalapril treatment in SHRE. Taken together, these results indicate that the impairment of the volume-sensitive, but not the

  19. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

    2004-01-01

    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  20. First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

    NARCIS (Netherlands)

    Pratt, JJ; de Wolf, BTHM; Mantingh, A

    2001-01-01

    Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

  1. Effects of Anterior Thalamic Nucleus Deep Brain Stimulation in Chronic Epileptic Rats

    Science.gov (United States)

    Amorim, Beatriz; Cavarsan, Clarissa; Miranda, Maisa Ferreira; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Nobrega, José N.; Mello, Luiz E.; Hamani, Clement

    2014-01-01

    Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy. In rodents, an increase in the latency for the development of seizures and status epilepticus (SE) has been reported in different animal models but the consequences of delivering stimulation to chronic epileptic animals have not been extensively addressed. We study the effects of anterior thalamic nucleus (AN) stimulation at different current intensities in rats rendered epileptic following pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery. Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 µsec. and either 100 µA or 500 µA. The frequency of spontaneous recurrent seizures in animals receiving stimulation was compared to that recorded in the preoperative period and in rats given sham treatment. To investigate the effects of DBS on hippocampal excitability, brain slices from animals receiving AN DBS or sham surgery were studied with electrophysiology. We found that rats treated with AN DBS at 100 µA had a 52% non-significant reduction in the frequency of seizures as compared to sham-treated controls and 61% less seizures than at baseline. Animals given DBS at 500 µA had 5.1 times more seizures than controls and a 2.8 fold increase in seizure rate as compared to preoperative values. In non-stimulated controls, the average frequency of seizures before and after surgery remained unaltered. In vitro recordings have shown that slices from animals previously given DBS at 100 µA had a longer latency for the development of epileptiform activity, shorter and smaller DC shifts, and a smaller spike amplitude compared to non-stimulated controls. In contrast, a higher spike amplitude was recorded in slices from animals given AN DBS at 500 µA. PMID:24892420

  2. Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats.

    Science.gov (United States)

    Zeggwagh, N-A; Ouahidi, M-L; Lemhadri, A; Eddouks, M

    2006-11-24

    The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (pInula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.

  3. Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord.

    Science.gov (United States)

    Wallace, M C; Tator, C H; Piper, I

    1987-06-01

    Direct current stimulation has been shown by others to enhance the regeneration of several types of tissues, including nervous tissue in some species. The purpose of the present experiment was to assess the value of direct current stimulation for enhancing the recovery of spinal cord function after clip compression injury of the rat spinal cord. Twenty Wistar rats underwent a 1-minute, 50-g clip compression injury at T-1, after which electrodes were placed epidurally with the anode proximal and the cathode distal to the injury site. These electrodes were attached to a stimulator implanted subcutaneously. Ten animals received stimulators that produced a constant current of 14 microA, and the remainder received stimulators with no electrical output and served as controls. Assignment of stimulators was random, and the treatment group was not identified until sacrifice. Neurological function was tested weekly for 15 weeks by the inclined plane technique, after which the animals were killed and the injured cords were examined for histological evidence of regeneration. The mean inclined plane result for the treatment group (39 +/- 5 degrees) was significantly better than that for the control group (31 +/- 6 degrees) (P less than 0.02), although there was no significant difference in histological findings between the two groups. Thus, direct current stimulation of the injured mammalian spinal cord produced improvement in neurological function and warrants further investigation.

  4. Molecular Mechanisms of Glucose-Stimulated GLP-1 Secretion From Perfused Rat Small Intestine

    DEFF Research Database (Denmark)

    Kuhre, Rune E.; Frost, Charlotte R.; Svendsen, Berit;

    2015-01-01

    Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w...... (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-d-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did...... not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations...

  5. Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle

    DEFF Research Database (Denmark)

    Wojtaszewski, Jørgen; Hansen, B F; Ursø, Birgitte

    1996-01-01

    The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin stimulat...

  6. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  7. Stimulation of DNA synthesis in cultured rat alveolar type II cells

    Energy Technology Data Exchange (ETDEWEB)

    Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

    1985-01-01

    Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated /sup 3/H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of /sup 3/H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture.

  8. Prefrontal Cortex and Neostriatum Self-Stimulation In the Rat : Differential Effects Produced by Apomorphine

    NARCIS (Netherlands)

    Mora, F.; Phillips, A.G.; Koolhaas, J.M.; Rolls, E.T.

    1976-01-01

    In a dose-response experiment, the effects of intraperitoneal injections of the dopamine receptor agonist, apomorphine (0.075, 0.15, 0.3, 0.6 and 1.2 mg/kg) were studied on self-stimulation elicited from electrodes implanted in the medial and sulcal prefrontal cortex and caudate-putamen in the rat.

  9. Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

    DEFF Research Database (Denmark)

    Rasch, Ruth; Jensen, B L; Nyengaard, Jens Randel

    1998-01-01

    In order to study the cellular mode of renin secretion, stereological methods were used to estimate number and volume of rat renin secretory granules during stimulation of the renin system. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min increased plasma renin concentration (PR...

  10. Dietary sodium stimulates ouabainlike activity in adrenalectomized spontaneously hypertensive rats.

    Science.gov (United States)

    Leenen, F H; Harmsen, E; Yu, H; Yuan, B

    1993-07-01

    Both the adrenal glands and the hypothalamus have been proposed to produce compound(s) with ouabainlike activity (OLA). To evaluate the contribution of the adrenal glands, 4-wk-old spontaneously hypertensive rats (SHR) were sham operated or adrenalectomized. The adrenalectomized SHR were given daily injections of corticosterone and aldosterone. Subsequently, rats were randomized to control or high (8%) dietary Na+, and after 2.5 wk, blood pressure and OLA in plasma, hypothalamus, and pituitary were evaluated. Hypertension developed somewhat less in adrenalectomized vs. sham-operated SHR. On control Na+ intake, adrenalectomy caused only minor decreases in circulating and central OLA. Adrenalectomy did not prevent the 50-90% increases in plasma, hypothalamus, and pituitary OLA caused by high Na+ intake for 2.5 wk. These findings are consistent with the concept that, at least in SHR, the central nervous system may represent the major source of both central and peripheral OLA.

  11. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Institute of Scientific and Technical Information of China (English)

    Jing ZHANG; Pei LI; Hai-fang GUO; Li LIU; Xiao-dong LIU

    2012-01-01

    Aim:To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker.Methods:The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats.PGE2 level in the rats was measured using an enzyme immunoassay.A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production.The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro.Results:Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats.Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats.The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac.No delay in the onset of inhibition was observed,suggesting that the effect compartment was located in the central compartment.An inhibitory effect sigmoid/max model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo.The /max model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro.Conclusion:Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats,but the pharmacodynamics of diclofenac is slightly affected.A PK-PD model characterizing an inhibitory effect sigmoid /max can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.

  12. Cytokine production of in vitro stimulated peripheral lymphocytes during the course of pregnancy and pseudopregnancy in the rat

    NARCIS (Netherlands)

    Faas, MM; Eenling, R; van der Schaaf, G; Moes, H; Heineman, MJ; Vos, P

    Problem Does maternal lymphocyte cytokine production after in vitro stimulation vary with the stage of pregnancy in the rat? Method of study Blood samples were taken during the estrus cycle in rats (n = 11). Thereafter, rats were rendered pregnant (n = 6) or pseudopregnant (n = 5) and blood samples

  13. Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

    OpenAIRE

    2009-01-01

    Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type re...

  14. Terminal effects of optogenetic stimulation on dopamine dynamics in rat striatum.

    Science.gov (United States)

    Bass, Caroline E; Grinevich, Valentina P; Kulikova, Alexandra D; Bonin, Keith D; Budygin, Evgeny A

    2013-04-15

    In this study, the first in-depth analysis of optically induced dopamine release using fast-scan cyclic voltammetry on striatal slices from rat brain was performed. An adeno-associated virus that expresses Channelrhodopsin-2 was injected in the substantia nigra. Tissue was collected and sectioned into 400μm-thick coronal slices 4 weeks later. Blue laser light (473nm) was delivered through a fiber optic inserted into slice tissue. Experiments revealed some difference between maximal amplitudes measured from optically and electrically evoked dopamine effluxes. Specifically, there was an increase in the amplitude of dopamine release induced by electrical stimulation in comparison with light stimulations. However, we found that dopamine release is more sensitive to changes in the pulse width in the case of optical stimulation. Light-stimulated dopamine was increased as the stimulation pulse widened. There was no difference with repeated stimulations at five minute intervals between stimulation sources and dopamine signal was stable during recording sessions, while one minute intervals resulted in a decline in the amplitude from both sources. Optical stimulation can also produce an artifact that is distinguishable from dopamine by the cyclic voltammogram. These results confirm that optical stimulation of dopamine is a sound approach for future pharmacological studies in slices.

  15. [Effect of a new opioid peptide on gastric secretion in the rat stimulated with 2-deoxyglucose].

    Science.gov (United States)

    Linari, G; Baldieri Linari, M; Castellacci, R

    1982-12-30

    Gastric secretion was studied in conscious rats with chronic gastric fistulae maintained in restraint cages. Experiments were performed 24 hours after surgical procedure: the stomachs were washed with 3 ml of saline and gastric acid determined by titration of pH 6 every 30 minutes. The i.v. injection of 75 mg/kg of 2DG strongly stimulated gastric secretion, with a 5-fold increase of acid output in comparison to control rats. The slow intravenous injection of dermorphin, 15 min before 2DG, dose-dependently inhibited the stimulant effect of the latter. Opioid activity of dermorphin has been reported (5); on the other hand, the intracerebroventricular injection of opiates has been shown to decrease the gastric secretion of the rat by Rozé et al. (3). The effectiveness of dermorphin given by intravenous route observed in present experiments seems to suggest the hypothesis that dermorphin (and other opiates) may act, besides central, also on peripheral sites.

  16. Forskolin inhibits the Gs-stimulated adenylate cyclase in rat ascites hepatoma AH66F cells.

    Science.gov (United States)

    Miyamoto, K; Sanae, F; Koshiura, R; Matsunaga, T; Hasegawa, T; Takagi, K; Satake, T

    1989-09-01

    Forskolin increased intracellular cyclic AMP and augmented cyclic AMP formation by prostaglandin E1 (PGE1) in normal rat hepatocytes and ascites hepatoma AH66 cells. However, in AH66F cells which were derived from the AH66 cell line, the diterpene only slightly increased the cyclic AMP level, and dose-dependently inhibited the accumulation caused by PGE1. Forskolin dose-dependently activated adenylate cyclase in these membranes, and the magnitude of activation by forskolin was largest in the following order: hepatocytes, AH66 cells, and AH66F cells. This difference may be based on the number of forskolin-binding sites. The binding affinity of forskolin for each cell membrane was similar. The number and affinity of forskolin-binding sites in these cells were not influenced by 5'-guanylylimidodiphosphate [Gpp(NH)p]. In hepatocytes and AH66 cells, forskolin and other adenylate cyclase activators such as PGE1, GTP, Gpp(NH)p, F-, and Mn2+ synergistically increased the enzyme activity. In AH66F cells, the forskolin-stimulated activity was hardly influenced by the GTP analog, and forskolin diminished the activities induced by the GTP analog in a manner similar to that of diterpene alone. Forskolin (10 microM) also significantly inhibited the activities induced by PGE1, GTP, and F-. The effect of forskolin with Mn2+ was additive in AH66F cells. The data suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide-binding protein and the catalytic unit in the membrane of normal hepatocytes and AH66 cells, but it interferes with the coupling in AH66F cells.

  17. Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.

    Science.gov (United States)

    Endoh, Hisashi; Fujioka, Takashi; Endo, Hideki; Inazuka, Yukiko; Furukawa, Susumu; Nakamura, Shoji

    2008-10-01

    The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

  18. Influence of gender and the oestrous cycle on in vitro contractile responses of the rat urinary bladder to cholinergic stimulation

    Science.gov (United States)

    Longhurst, Penelope A; Levendusky, Mark

    2000-01-01

    Experiments were done to determine the influence of gender and the oestrous cycle on rat urinary bladder contractility in response to cholinergic stimulation. Bladder strips from female rats responded to high frequency stimulation with smaller contractile responses than did strips from males, and to low concentrations of carbachol with greater responses. The decreased responsiveness of bladder strips from female rats to electrical field stimulation can be primarily attributed to the rats in the oestrous stage of the oestrous cycle. Bladder strips from female rats in all stages of the oestrous cycle were more sensitive to carbachol than those from males, but there were no differences in sensitivity to electrical field stimulation. The contractile responses of strips from both male and female rats to carbachol were antagonized by muscarinic antagonists with the following rank order of affinity (pA2) estimates: 4-DAMP>>pirenzepine>methoctramine, suggesting that the receptor mediating contraction was the M3 subtype. There were no differences in pA2 values between bladder strips from male and female rats. The data indicate that responsiveness of bladder strips to electrical field stimulation and carbachol is altered in female rats in the oestrous stage of the oestrous cycle. Furthermore, gender influences the sensitivity of rat bladder to muscarinic stimulation. PMID:10991909

  19. Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

    Science.gov (United States)

    Linderman, Jon K.; Whittall, Justen B.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Booth, Frank W.; Grindeland, Richard E.

    1995-01-01

    The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

  20. Soybean isoflavones alter parvalbumin in hippocampus of mid-aged normal female, ovariectomized female, and normal male rats

    Institute of Scientific and Technical Information of China (English)

    In Koo HWANG; Moo Ho WON; Yoon-bok LEE; Ki-yeon YOO; Tae-cheon KANG; Soon Sung LIM; Sang Moo KIM; Heon-soo SOHN; Woo-jung KIM; Hyun Kyung SHIN

    2006-01-01

    Aim: To investigate the long-term effect of soybean isoflavones on changes in parvalbumin (PV) immunoreactivity in the hippocampus in normal female, ovariectomized (OVX) female and normal male rats. Methods: Ten-month-old rats were assigned to one of 9 groups (n=7 in each group) based on body weight using arandomized complete-block design. The groups were: control diet-treated females,OVX females, and males; 0.3 g/kg isoflavone-treated females, OVX females, and males; and 1.2 g/kg isoflavone-treated females, OVX females, and males. The PV immunostaining was conducted by using the standard avidin-biotin complex method. Results: PV immunoreactivity and the number of PV-immunoreactive neurons in all the groups after isoflavone treatment were significantly changed in the hippocampal CA1 region and in the dentate gyrus, but not in the hippocampal CA2/3 region. PV immunoreactivity and the number of PV-immunoreactive neurons in the control diet OVX females were similar to those in the control diet, and were greater than those in the control diet normal females. PV immunoreactivity and the number of PV-immunoreactive neurons in all the isoflavone-treated groups decreased dose-dependently after isoflavone treatment. Conclusion: Long-term administration of isoflavones may induce a reduction of PV in interneurons in the hippocampal CA1 region and in the dentate gyrus. The reduction of PV in these regions suggests that the long-term administration of isoflavones may cause a change in calcium homeostasis in the hippocampal CA1 region and in the dentate gyrus.

  1. Evaluation of an oral insulin formulation in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Hossein Najafzadeh

    2012-01-01

    Full Text Available Aim: As injection is not an ideal means for insulin delivery, various attempts have been made to administer insulin orally until now. The development of an oral dosage form of insulin would help diabetic patients and make the treatment more convenient. The aim of the present study is to evaluate the effectiveness of an oral insulin formulation containing polar and non-polar ingredients. Materials and Methods: New excipient for oral insulin administration in normal and diabetic rats was evaluated by measuring blood glucose concentrations in two groups (10 rats each of normal and streptozotocin-induced diabetic rats. Oral insulin was administrated and blood glucose was measured by glucometer at 0, 1, 2, 3 and 4 h post-feeding. The data was compared by Student′s t test. Results: Oral insulin formulation significantly (P<0.05 reduced blood glucose from 100 mg/dl to 33.73 mg/dl and 451.66 mg/dl to 200.83 mg/dl at 4 h in normal and diabetic rats, respectively. Conclusion: The novel excipient used could protect insulin from gastric and pancreatic enzymes and reduce blood glucose concentration in both healthy and diabetic rats suggesting that oral delivery of insulin is feasible in a near future.

  2. Functional Electrical Stimulation Helps Replenish Progenitor Cells in the Injured Spinal Cord of Adult Rats

    Science.gov (United States)

    Becker, Daniel; Gary, Devin S.; Rosenzweig, Ephron S.; Grill, Warren M.; McDonald, John W.

    2010-01-01

    Functional electrical stimulation (FES) can restore control and offset atrophy to muscles after neurological injury. However, FES has not been considered as a method for enhancing CNS regeneration. This paper demonstrates that FES dramatically enhanced progenitor cell birth in the spinal cord of rats with a chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb movement was implanted into these rats. Twelve identically-injured rats received inactive FES implants. An additional control group of uninjured rats were also examined. Ten days after FES implantation, dividing cells were marked with bromodeoxyuridine (BrdU). The ‘cell birth’ subgroup (half the animals in each group) was sacrificed immediately after completion of BrdU administration, and the ‘cell survival’ subgroup was sacrificed 7 days later. In the injured ‘cell birth’ subgroup, FES induced an 82-86 % increase in cell birth in the lumbar spinal cord. In the injured ‘cell survival’ subgroup, the increased lumbar newborn cell counts persisted. FES doubled the proportion of the newly-born cells which expressed nestin and other markers suggestive of tripotential progenitors. In uninjured rats, FES had no effect on cell birth/survival. This report suggests that controlled electrical activation of the CNS may enhance spontaneous regeneration after neurological injuries. PMID:20059998

  3. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats.

    Science.gov (United States)

    Todtenkopf, Mark S; Marcus, Jacqueline F; Portoghese, Philip S; Carlezon, William A

    2004-04-01

    Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced activity of brain reward systems. Furthermore, each effect appears due to increases in CREB-mediated expression of dynorphin, since each is attenuated by intracranial injections of the kappa-opioid receptor antagonist norBNI. Intracranial self-stimulation (ICSS) studies were conducted in rats to determine whether administration of a kappa-agonist would have depressive-like effects on brain stimulation reward, and whether pretreatment with a kappa-antagonist would attenuate any such effects. Conditions that have depressive effects in people (e.g., drug withdrawal) increase the threshold amounts of stimulation required to sustain ICSS in rats. Sprague-Dawley rats with lateral hypothalamic stimulating electrodes were tested in a "curve-shift" variant of the ICSS procedure after systemic administration of the kappa-agonist U-69593 alone, the novel kappa-antagonist 5'-acetamidinoethylnaltrindole (ANTI) alone, or co-administration of both drugs. U-69593 dose dependently increased ICSS thresholds, suggesting that activation of kappa-receptors reduced the rewarding impact of the brain stimulation. ANTI had no effects on its own, but it attenuated increases in ICSS thresholds caused by the agonist. These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own.

  4. Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, M.V.; Sayeed, M.M.

    1988-04-01

    Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of /sup 14/C-labeled 3-O-methylglucose (/sup 14/C-3-MG) after loading muscles with /sup 14/C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated /sup 14/C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters.

  5. Hypoglycemic and antiperglycemic effects of Semecarpus anacardium linn in normal and alloxan-induced diabetic rats.

    Science.gov (United States)

    Kothai, R; Arul, B; Kumar, K Suresh; Christina, A J M

    2005-01-01

    The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose level was investigated in both normal and alloxan induced diabetic rats. The blood glucose levels were measured at 0, 1, 2 and 3 hours after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rat from 84 +/- 1.4 to 67 +/- 1.7 mg/dl, 3 hours after oral administration of the extract (P < 0.05). It also significantly lowered blood glucose level in alloxan induced diabetic rat from 325 +/- 2.2 to 144 +/- 1.4 mg/dl, 3 hours after oral administration of the extract (P < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, an oral hypoglycemic agent.

  6. Hypoglycemic and antihyperglycemic effect of Semecarpus anacardium Linn in normal and streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Arul, B; Kothai, R; Christina, A J M

    2004-12-01

    The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose was investigated in both normal (hypoglycemic) and streptozotocin-induced diabetic (antihyperglycemic) rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rats from 85.83 +/- 1.55 to 65.83 +/- 2.20 mg/dl, 3 h after oral administration of the extract (p < 0.05). It also significantly lowered blood glucose levels in streptozotocin-induced diabetic rats from 335.33 +/- 4.90 to 132.17 +/- 4.49 mg/dl, 3 h after oral administration of the extract (p < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, a sulfonyl urea derivative used in diabetes mellitus. 2004 Prous Science

  7. Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Cabrera, W; Genta, S; Said, A; Farag, A; Rashed, K; Sánchez, S

    2008-03-01

    The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could be potentially useful for post-prandial hyperglycemia treatment.

  8. Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

    NARCIS (Netherlands)

    Ormai, S.; Hagenbeek, A.; Palkovits, M.; Bekkum, D.W. van

    1973-01-01

    The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administra

  9. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  10. Expression of PirB in normal and injured spinal cord of rats.

    Science.gov (United States)

    Zhou, Yingchun; Qian, Rongjun; Rao, Jing; Weng, Mixia; Yi, Xuxia

    2010-08-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expression of PirB was obviously increased, and that in the injured spinal cord from the first day to the 10th day was significantly higher than in the normal spinal cord. The positive expression of PirB in neurons from different regions of gray matter of the injured spinal cord was seen. It was concluded that the expression of PirB in the normal spinal cord of rats was low. The expression of PirB in SCI was significantly increased till at least the 10th day.

  11. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  12. comparison of serum visfatin levels in restricted diet rats,type2 diabetic rats and insulin resistance rats with normal rats

    Directory of Open Access Journals (Sweden)

    mohammadali ghaffari

    2015-11-01

    Full Text Available Background and Purpose: Adipose tissue is not only a site of triglycerides storage, but also an active endocrine organ that secretes many biologically active mediators refered to as "adipokines". Visfatin, as a new adipokine has an important role in Homeostasis of energy and glucose metabolism. In the present study serum visfatin levels in restricted diet rats,type2 diabetic rats and insulin resistant rats has been measured and compared with control group. relationship between Visfatin and blood sugar, lipid profile, insulin, and HOMA-IR in these groups has been investigated Methods and Materials: 32 male wistar rats were divided into 4 groups (8 rats in each group.group 1 was control,with free access to diet, group 2 or restricted diet group using 65% of normal diet , group3 orinduced type2 diabetic group with nicotinamide and streptozocin and group 4 was insulin resistance ,induced with fructose diet. After 6 weeks animals weight and other biochemical factors such as FBS (Fasting Blood Sugar, lipid profile, insulin and visfatin were measured. Results of this study were analyzed using SPSS16.and then examined and reported as ±average of standard deviation. Values of p< 0.05 were considered statistically significant . Results: Results of this study showed that body weight increased in all groups except diabetic group. Triglyceride were increased in all groups, in this order,restricted diet, control, insulin resistance and diabetic groups. visfatin, insulin, and Homa-IR increase significantly in type 2 diabetic rats and insulin resistant group. Conclusion: There was a positive and significant relationship between visfatin and HOMA-IR, and between visfain and FBS (Fasting Blood Sugar, while there was a negative relationship between visfatin and insulin, but this relationship was not significant.

  13. Normalization of ventral tegmental area structure following acupuncture in a rat model of heroin relapse

    Institute of Scientific and Technical Information of China (English)

    Rongjun Zhang; Xinghui Cai; Xiaoge Song; Chaoyang Dong; Xiaorong Hou; Lei Lv

    2014-01-01

    Drugs can cause obvious damage to the brain. To verify the relationship between acupuncture, neurotrophic factor expression and brain cell structural changes, this study established a rat model of heroin relapse using intramuscular injection of increasing amounts of heroin. During the detoxiifcation period, rat models received acupuncture at Baihui (DU20) and Dazhui (DU14). Electron microscopy demonstrated that the structure of the ventral tegmental area in heroin relapse rats gradually became normalized after acupuncture treatment. Immunohistochem-ical staining exhibited that the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the ventral tegmental area following acupuncture. Moreover, the effects were similar to that of methadone, a type of medicine called an opioid. Results suggested that acupuncture at Baihui and Dazhui protected brain neurons against injury in rats with heroin relapse by promoting brain-derived neurotrophic factor and glial cell line-de-rived neurotrophic factor expression.

  14. High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.

    Science.gov (United States)

    Lambrinoudaki, Irene; Armeni, Eleni; Rizos, Demetrios; Georgiopoulos, Georgios; Kazani, Maria; Alexandrou, Andreas; Deligeoroglou, Efthymios; Livada, Alexandra; Psychas, Charalampos; Creatsa, Maria; Bouboulis, George; Alevizaki, Maria; Stamatelopoulos, Kimon

    2012-03-01

    Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.

  15. In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

    Science.gov (United States)

    Choi, J. W.; Shin, S. C.; Kim, S.; Chung, E. R.; Bang, J. H.; Cho, G. I.; Choi, S. D.; Park, Y. S.; Jang, T. S.; Yoo, Y. M.; Lee, S. S.; Hwang, D. G.

    2010-05-01

    In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequence of the cytokine genes, such as the tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.

  16. HISTOCHEMICAL AND ELECTRON-MICROSCOPIC CHARACTERIZATION OF HEPATIC MACROPHAGE SUBFRACTIONS ISOLATED FROM NORMAL AND LIPOSOMAL MURAMYL DIPEPTIDE TREATED RATS

    NARCIS (Netherlands)

    HOEDEMAKERS, RMJ; ATMOSOERODJOBRIGGS, JE; MORSELT, HWM; DAEMEN, T; SCHERPHOF, GL; HARDONK, MJ

    1995-01-01

    Subfractions of the hepatic macrophage population, differing in cell size, were isolated from normal rats and rats treated with liposomal muramyl dipeptide (lipMDP) and analyzed histochemically and by ultrastructural peroxidase cytochemistry. The majority of cells in all subfractions of control rats

  17. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    Science.gov (United States)

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life.

  18. Acupuncture Stimulation Alleviates Corticosterone-Induced Impairments of Spatial Memory and Cholinergic Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Bombi Lee

    2012-01-01

    Full Text Available The purpose of this study was to examine whether acupuncture improves spatial cognitive impairment induced by repeated corticosterone (CORT administration in rats. The effect of acupuncture on the acetylcholinergic system was also investigated in the hippocampus. Male rats were subcutaneously injected with CORT (5 mg/kg once daily for 21 days. Acupuncture stimulation was performed at the HT7 (Sinmun acupoint for 5 min before CORT injection. HT7 acupoint is located at the end of transverse crease of ulnar wrist of forepaw. In CORT-treated rats, reduced spatial cognitive function was associated with significant increases in plasma CORT level (+36% and hippocampal CORT level (+204% compared with saline-treated rats. Acupuncture stimulation improved the escape latency for finding the platform in the Morris water maze. Consistently, the acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and mRNA expression of BDNF and CREB in the hippocampus. These findings demonstrate that stimulation of HT7 acupoint produced significant neuroprotective activity against the neuronal impairment and memory dysfunction.

  19. Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis

    Science.gov (United States)

    Inayat, Samsoon; Rountree, Corey M.; Troy, John B.; Saggere, Laxman

    2015-02-01

    Objective. No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ˜ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter

  20. Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol.

    Science.gov (United States)

    Smith, Brennan K; Perry, Christopher G R; Herbst, Eric A F; Ritchie, Ian R; Beaudoin, Marie-Soleil; Smith, Jeffrey C; Neufer, P Darrell; Wright, David C; Holloway, Graham P

    2013-12-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the aetiology of skeletal muscle insulin resistance, although there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturating ADP, but ATP turnover and the resultant ADP is thought to limit respiration in vivo. Therefore, we investigated the potential link between submaximal ADP-stimulated respiration rates, ROS generation and skeletal muscle insulin sensitivity in a model of type 2 diabetes mellitus, the ZDF rat. Utilizing permeabilized muscle fibres we observed that submaximal ADP-stimulated respiration rates (250-2000 μm ADP) were lower in ZDF rats than in lean controls, which coincided with decreased adenine nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP-stimulated respiration occurred in the absence of a decrease in electron transport chain function. Treating ZDF rats with resveratrol improved skeletal muscle insulin resistance and this was associated with elevated submaximal ADP-stimulated respiration rates as well as an increase in ANT2 protein content. These results coincided with a greater ability of ADP to attenuate mitochondrial ROS emission and an improvement in cellular redox balance. Together, these data suggest that mitochondrial dysfunction is present in skeletal muscle insulin resistance when assessed at submaximal ADP concentrations and that ADP dynamics may influence skeletal muscle insulin sensitivity through alterations in the propensity for mitochondrial ROS emission.

  1. Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats

    Directory of Open Access Journals (Sweden)

    Panunzi Simona

    2003-09-01

    Full Text Available Abstract Background Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. Methods Sixty-four rats were randomized in two groups and laparotomized. One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline. Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured. Body weight, food and water intake were also recorded daily. Results HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 ± 90.25 micromol HCl vs. 1247 ± 152. P = 0.0017. Botulinum toxin-treated rats also showed significantly lower food intake and weight gain. Conclusions Botulinum toxin type A reduces stimulated gastric acidity. This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses. Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility.

  2. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  3. Spontaneous and electrochemically stimulated changes in plasma LH in the female rat following hypothalamic deafferentation.

    Science.gov (United States)

    Phelps, C P; Krieg, R J; Sawyer, C H

    1976-01-16

    Plasma LH levels in adult female rats were studied by radioimmunoassay 6 weeks after making frontal cuts (FC) at the optic chiasm with Halász knives of various sizes. Cuts made with a small knife (radius 1.3 mm) permitted a spontaneous rise in plasma LH during proestrus from a mean of 96 +/- 25 ng/ml at 14:00 h to 545 +/- 207 ng/ml at 18:00 h in 13 rats. Seven of the latter, with a mean plasma LH of 967 +/- 281 ng/ml at 18:00 h exhibited tubal ova at hemicastration (hemi-ovx) the following morning. In a similar experiment 6 FC females lesioned with a 1.5 mm knife had plasma LH levels of 53 +/- 7 ng/ml at 14:00 h, but showed neither detectable changes at 2 h intervals through 20:00 h nor ovulation at hemi-ovx. Similar results were obtained in 13 rats deafferented with a 2.0 mm knife. Nine weeks after FC and 3 weeks following hemi-ovx all animals were given pentobarbital (32 mg/kg i.p.) at 13:30 h and stimulated bilaterally in the medial preoptic area (MPO) passing 20 muA anodal DC X 60 sec through concentric bipolar steel electrodes placed 0.8 mm from the midline. All 3 groups of FC animals showed increases in plasma LH to comparable levels (range: 197 +/- 45-357 +/- 156 ng/ml) 1 h after stimulation. Electrochemical stimulation sites extended lateral to the cut locations on at least one side in all animals. The results of these studies suggest that chronically (9 week) deafferented female rats have the capacity to release pituitary LH in response to MPO electrochemical stimulation in spite of retrochiasmatic deafferentation, but that the ovaries of the persistent estrus rat are unresponsive to these amounts of circulating LH.

  4. Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight was performed in normal and postinflammation irritable bowel syndrome (PI-IBS rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as Cmax⁡, AUC(0–t, Vd/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status.

  5. Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

    Science.gov (United States)

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Wang, Yinghan; Yang, Qing; Guo, Yan; Weng, Xiaogang; Gao, Shuangrong; Wang, Hailin; Zhu, Xiaoxin; Dong, Yu; Li, Yujie; Wang, Yajie

    2014-01-01

    A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight) was performed in normal and postinflammation irritable bowel syndrome (PI-IBS) rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as C max⁡, AUC(0–t), V d/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status. PMID:25309613

  6. Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats.

    Science.gov (United States)

    El Hilaly, Jaouad; Lyoussi, Badiâa

    2002-05-01

    The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337+/-9.3 to 102.2+/-17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112+/-14.4 mg/dl at 1 week vs 337+/-9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.

  7. Effects of vagus nerve stimulation on parafascicular nucleus neuronal activities in rats

    Institute of Scientific and Technical Information of China (English)

    Yizhe Meng; Jinju Jiao

    2008-01-01

    BACKGROUND: Vagal nerve fibers have many projections to the central nervous system. The anti-epileptic effects of vagus nerve stimulation (VNS) are associated with the thalamus, insular cortex, and other brain regions.OBJECTIVE: To validate the inhibitory effects of vagus nerve stimulation on firing activities of parafascicular nucleus (Pf) neurons in rats. DESIGN, TIME, AND SETTING: The experiment was performed in the Electrophysiological Laboratory of Department of Neurobiology, Liaoning Medical University between September 2006 and September 2007 with multiple-factor self-controlled design.MATERIALS: Twenty-two healthy adult male Sprague Dawley rats were obtained for this experiment. Main instruments: A320R constant electrical stimulation was made by United States World Precision Instruments, Spike2 Biological Signal Processing Systems was provided by British CED Company.METHODS: Under general anesthesia, the left cervical vagus nerve of rats was separated by approximately 1.0 cm. A stimulation electrode was deployed on the vagus nerve, with various settings for VNS parameters.MAIN OUTCOME MEASURES: ① Firing rates of Pf before and after various VNS parameters were measured according to effect (R) ≥ 20%: excited effect, R ≤ -20%: inhibited effect, -20% < R < 20%: no effect. ② Firing rates of excited Pf neurons after various VNS parameters were measured.RESULTS: ① One rat died prior to recording, another was recorded in the wrong brain location, but the remaining 20 rats were included in the final analysis. ② A total of 221 Pf neurons in healthy rats were recorded. The spontaneous firing rats were (6.70 ± 0.56) Hz and varied between 0.34-52.5 Hz. The spontaneous firing rates were significantly increased in 146 neurons (66.1%), increasing from (5.36 ± 0.59) Hz to (8.22 ± 0.81) Hz (P < 0.01). A total of 40 (18.1%) neurons did not respond, and 35 (15.8%) neurons were inhibited. ③ The excitation rates of Pf neurons did not increase with increasing

  8. Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men.

    OpenAIRE

    Van Cauter, E; Plat, L; Scharf, M B; R Leproult; Cespedes, S; L'Hermite-Balériaux, M; Copinschi, G..

    1997-01-01

    The aim of this study was to investigate, in normal young men, whether gamma-hydroxybutyrate (GHB), a reliable stimulant of slow-wave (SW) sleep in normal subjects, would simultaneously enhance sleep related growth hormone (GH) secretion. Eight healthy young men participated each in four experiments involving bedtime oral administration of placebo, 2.5, 3.0, and 3.5 g of GHB. Polygraphic sleep recordings were performed every night, and blood samples were obtained at 15-min intervals from 2000...

  9. Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1984-10-01

    When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Thromboxane A(2 receptor stimulation promotes closure of the rat ductus arteriosus through enhancing neointima formation.

    Directory of Open Access Journals (Sweden)

    Tomohiro Yokota

    Full Text Available Ductus arteriosus (DA closure follows constriction and remodeling of the entire vessel wall. Patent ductus arteriosus occurs when the DA does not close after birth, and this condition is currently treated using cyclooxygenase inhibitors. However, the efficacy of cyclooxygenase inhibitors is often limited. Our previous study demonstrated that low-dose thromboxane A2 receptor (TP stimulation constricted the DA with minimal adverse effects in rat neonates. However, its effect on DA remodeling remains unknown. In this study, we focused on the impact of the exogenous TP stimulation on the DA remodeling, especially intimal thickening. Using DA explants from rat fetuses at embryonic day 19 as a ex vivo model and primary cultured rat DA smooth muscle cells from embryonic day 21 as a in vitro model, we evaluated the effect of TP stimulation on the DA remodeling. The selective TP agonists U46619 and I-BOP promoted neointima formation in the ex vivo DA explants, and TP stimulation increased DA SMC migration in a dose-dependent manner. Both effects were inhibited by the selective TP antagonist SQ29548 or the siRNA against TP. TP stimulation also increased DA SMC proliferation in the presence of 10% fetal bovine serum. LC/MS/MS analysis revealed that TP stimulation increased secretion of several extracellular matrix proteins that may contribute to an increase in neointima formation. In conclusion, we uncovered that exogenous administration of TP agonist promotes neointima formation through the induction of migration and proliferation of DA SMC, which could contribute to DA closure and also to its vasoconstrictive action.

  11. A wearable stimulation bandage for electrotherapy studies in a rat ischemic wound model.

    Science.gov (United States)

    Howe, Daniel S; Dunning, Jeremy L; Henzel, Mary K; Graebert, Jennifer K; Bogie, Kath M

    2011-01-01

    The clinical efficacy of electro-therapy in the treatment of chronic wounds is currently debated, and a in-vivo evaluation of stimulation parameters will provide the statistical evidence needed to direct clinical guidelines. A low-cost, wearable electrical stimulation bandage has been developed for use with an established rat ischemic wound model. The bandage consists of a user-programmable stimulator PCB and a plastic bandage with two hydrogel electrodes. The battery-powered bandage may be used for up to seven days between dressing changes, and the stimulator may be reused. The microcontroller-based stimulator uses a boost converter circuit to generate pulses up to 90 V from a 3 V coin cell battery. Consistent operation of the boost converter over the wide input and output voltage ranges is achieved using voltage feedforward and soft-start techniques implemented in firmware. The bandages are laser-cut to shape, and electrical traces are applied using stencils and conductive nickel paint. Both the PCB and electrical traces are encapsulated to protect the animal. The device has been successfully demonstrated using the rat ischemic wound model for a period of seven days, and clinical experiments are ongoing.

  12. Histamine H1 and endothelin ETB receptors mediate phospholipase D stimulation in rat brain hippocampal slices.

    Science.gov (United States)

    Sarri, E; Picatoste, F; Claro, E

    1995-08-01

    Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans-(1S,3R)-aminocyclopentyl-1,3-dicarboxylic acid (trans-ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32P]Pi-prelabeled rat brain cortical and hippocampal slices. The accumulation of [32P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans-ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 microM) was inhibited by the H1 receptor antagonist mepyramine with a Ki constant of 0.7 nM and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 nM) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 nM, respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively.

  13. Impact of anesthesia on valvular function in normal rats during echocardiography.

    Science.gov (United States)

    Droogmans, Steven; Lauwers, Rinaldo; Cosyns, Bernard; Roosens, Bram; Franken, Philippe R; Weytjens, Caroline; Bossuyt, Axel; Lahoutte, Tony; Schoors, Danny; Van Camp, Guy

    2008-10-01

    Anesthetic agents have different effects on hemodynamic and cardiac functional parameters. The influence of these changes on valvular function has not been studied in small animals. For this purpose, 48 male Wistar rats were divided into three equal groups. An echocardiogram was performed under inhaled isoflurane 2% gas (group I) or under intraperitoneal pentobarbital 50 mg/kg (group II) or ketamine/xylazine (group III) 40/8 mg/kg. Aortic regurgitation was only found in group III (80%, p anesthesia causes hemodynamic changes that may result in functional valvular regurgitations in normal rats.

  14. Characteristics of the norepinephrine-stimulated phosphatidylinositol turnover in rat pineal cell dispersions

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, G.; Smith, T.L.

    1981-10-01

    Dispersed rat pineal cells can be used for the study of the phosphatidylinositol effect. The response to ( - )-norepinephrine of the incorporation of 32Pi into phospholipids is linear with time and cell concentration, stereospecific, and mediated through alpha-1-adrenergic receptors. Na+ in the incubation medium is obligatory for labeling of phosphatidylinositol and phosphatidylcholine by 32P. In the absence of K+, incorporation of 32P is drastically lowered and no stimulation by norepinephrine occurs. Rb+ can replace K+. Omission of Ca2+ or substitution with Sr2+ preferentially lowers incorporation of radioactivity into phosphatidylcholine. Mg2+ is not required for basal or stimulated labeling.

  15. A PARYLENE-BASED MICROELECTRODE ARRAY IMPLANT FOR SPINAL CORD STIMULATION IN RATS.

    Science.gov (United States)

    Nandra, Mandheerej S; Lavrov, Igor A; Edgerton, V Reggie; Tai, Yu-Chong

    2011-01-23

    The design and fabrication of an epidural spinal cord implant using a parylene-based microelectrode array is presented. Rats with hindlimb paralysis from a complete spinal cord transection were implanted with the device and studied for up to eight weeks, where we have demonstrated recovery of hindlimb stepping functionality through pulsed stimulation. The microelectrode array allows for a high degree of freedom and specificity in selecting the site of stimulation compared to wire-based implants, and triggers varied biological responses that can lead to an increased understanding of the spinal cord and locomotion recovery for victims of spinal cord injury.

  16. Biochemical analysis of the response in rat bone marrow cell cultures to mechanical stimulation.

    Science.gov (United States)

    Yoshikawa, T; Peel, S A; Gladstone, J R; Davies, J E

    1997-01-01

    Bone marrow cells obtained from rat femora were subjected to primary culture with 15% fetal bovine serum in the presence of 10(-8) M dexamethasone, and following trypsin treatment 5 days later were seeded on Petriperm dishes which have a flexible bottom. After a 2-day subculture, a cyclic stress consisting of a 1 s stretch (0.3% strain. 0.5 Hz) and a 1 s relaxation for 30 min every day was started. Culture tissue was removed on day 2 of the subculture (immediately prior to start of stimulation), and then on days 5 and 8 (3 and 6 days after the start of stimulation, respectively), at which times dry weight, DNA, alkaline phosphatase (ALP) activity, and bone Gla protein (BGP, osteocalcin) were measured. Both the dry weight and DNA showed a significant increase in the stimulated group by day 8, while the ALP activity showed a significant increase by day 5. The BGP began to increase in the stimulated group on day 5 in contrast to the control group in which it only increased on day 8. These results support the contention that mechanical stimulation promotes the differentiation of osteogenic cells and enhances bone formation. Since in this experimental model the acceleration of bone formation by mechanical stimulation can be reproduced in vitro, it is extremely useful for investigating the mechanisms underlying mechanical stimulation.

  17. [Action of adaptogens: cucurbitacin R diglucoside as a stimulator of arachidonic acid metabolism in the rat adrenal gland].

    Science.gov (United States)

    Panosian, A G; Dadaian, M A; Gevorkian, G A

    1989-01-01

    It has been demonstrated that cucurbitacin R diglucoside (CRD), an adaptogen increasing the rat working capacity and stimulating corticosteroid secretion, stimulates the release of arachidonic acid (AA) in the rat adrenal cortex in vivo (the administration of CRD during 14 days) as well as in vitro (the incubation of isolated rat adrenocortical cells with CRD in the presence of eicosatetraenoic acid, the AA metabolism inhibitor) experiments. The incubation of isolated rat adrenocortical cell with CRD in the presence of AA increases the biosynthesis of 5-HETE, the precursor of which 5-HPETE is known to be a modulator of ACTH-induced corticosteroid secretion.

  18. Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats.

    Science.gov (United States)

    Lima, Lívia P; Barros, Inês A; Lisbôa, Patrícia C; Araújo, Renata L; Silva, Alba C M; Rosenthal, Doris; Ferreira, Andrea C F; Carvalho, Denise P

    2006-08-01

    Sex steroids interfere with the pituitary-thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demonstrate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a significant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal.

  19. Iridium oxide microelectrode arrays for in vitro stimulation of individual rat neurons from dissociated cultures.

    Science.gov (United States)

    Eick, Stefan; Wallys, Jens; Hofmann, Boris; van Ooyen, André; Schnakenberg, Uwe; Ingebrandt, Sven; Offenhäusser, Andreas

    2009-01-01

    We present the first in vitro extracellular stimulation of individual neurons from dissociated cultures with iridium oxide (IrO(x)) electrodes. Microelectrode arrays with sputtered IrO(x) films (SIROF) were developed for electrophysiological investigations with electrogenic cells. The microelectrodes were characterized with scanning electron and atomic force microscopy, revealing rough and porous electrodes with enlarged surface areas. As shown by cyclic voltammetry and electrochemical impedance spectroscopy, the large surface area in combination with the good electrochemical properties of SIROF resulted in high charge storage capacity and low electrode impedance. Thus, we could transfer the good properties of IrO(x) as material for in vivo stimulation electrodes to multi-electrode arrays with electrode diameters as small as 10 mum for in vitro applications. Single rat cortical neurons from dissociated cultures were successfully stimulated to fire action potentials using single or trains of biphasic rectangular voltage-controlled stimulation pulses. The stimulated cell's membrane potential was simultaneously monitored using whole-cell current-clamp recordings. This experimental configuration allowed direct evaluation of the influence of pulse phase sequence, amplitude, and number on the stimulation success ratio and action potential latency. Negative phase first pulses were more effective for extracellular stimulation and caused reduced latency in comparison to positive phase first pulses. Increasing the pulse amplitude also improved stimulation reliability. However, in order to prevent cell or electrode damage, the pulse amplitude is limited to voltages below the threshold for irreversible electrochemical reactions at the electrode. As an alternative to increasing the amplitude, a higher number of stimulation pulses was also shown to increase stimulation success.

  20. Iridium oxide microelectrode arrays for in vitro stimulation of individual rat neurons from dissociated cultures

    Directory of Open Access Journals (Sweden)

    Stefan Eick

    2009-11-01

    Full Text Available We present the first in-vitro extracellular stimulation of individual neurons from dissociated cultures with iridium oxide (IrOx electrodes. Microelectrode arrays with sputtered IrOx films (SIROF were developed for electrophysiological investigations with electrogenic cells. The microelectrodes were characterized with scanning electron and atomic force microscopy, revealing rough and porous electrodes with enlarged surface areas. As shown by cyclic voltammetry and electrochemical impedance spectroscopy, the large surface area in combination with the good electrochemical properties of SIROF resulted in high charge storage capacity and low electrode impedance. Thus, we could transfer the good properties of IrOx as material for in-vivo stimulation electrodes to MEAs with electrode diameters as small as 10 µm for in-vitro applications. Single rat cortical neurons from dissociated cultures were successfully stimulated to fire action potentials using single or trains of biphasic rectangular voltage-controlled stimulation pulses. The stimulated cell’s membrane potential was simultaneously monitored using whole-cell current-clamp recordings. This experimental configuration allowed direct evaluation of the influence of pulse phase sequence, amplitude, and number on the stimulation success ratio and action potential latency. Negative phase first pulses were more effective for extracellular stimulation and caused reduced latency in comparison to positive phase first pulses. Increasing the pulse amplitude also improved stimulation reliability. However, in order to prevent cell or electrode damage, the pulse amplitude is limited to voltages below the threshold for irreversible electrochemical reactions at the electrode. As an alternative to increasing the amplitude, a higher number of stimulation pulses was also shown to increase stimulation success.

  1. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  2. Depolarization-stimulated /sup 42/K+ efflux in rat aorta is calcium- and cellular volume-dependent

    Energy Technology Data Exchange (ETDEWEB)

    Magliola, L.; Jones, A.W.

    1987-07-01

    The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase /sup 42/K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated /sup 36/Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated /sup 42/K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated /sup 42/K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit /sup 42/K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated /sup 42/K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the /sup 42/K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated /sup 42/K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists.

  3. Opiate modification of intracranial self-stimulation in the rat.

    Science.gov (United States)

    Weibel, S L; Wolf, H H

    1979-01-01

    Studies were conducted to confirm the involvement of central opiate receptors in the expression of opiate modulation of intracranial self-stimulation (ICSS). Biphasic, dose-related changes in ICSS responding are described following IP administration of morphine sulfate (1-25 mg/kg) and levorphanol tartrate (LEV, 0.5-5 mg/kg). Similar patterns of response modification are reported following intraventricular (IVt) administration of LEV (0.01-0.2 muMoles) LEV's enantiomorph, dextrorphan, was not found to elicit comparable effects after either IP or IVt administration. Both the facilitatory and the depressant phases of LEV's action were antagonized by naltrexone (10 microgram, IVt), which had no apparent effect on ICSS by itself. Complete tolerance developed to the suppression of responding by 2.5 mg/kg LEV (IP) but not to the facilitatory effect of 0.5 mg/kg (IP), during a 5-day course of administration. The implications of these results for opiate reinforcement theory are discussed and possible mechanisms are advanced.

  4. Evaluation of wound healing potential of Pterocarpus marsupium heart wood extract in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhal

    2012-01-01

    Full Text Available Aim: The aim of the present study is to evaluate and compare the cutaneous wound healing potential of Pterocarpus marsupium in normal and diabetic rats and make inference for the cutaneous wound healing potential by possible "mode of action" P. marsupium extract. Materials and Methods: The effect of heart wood extract of P. marsupium on wound healing has been studied in diabetic and normal animals. The effect has also been compared with standard (mupirocin ointment application. In the absence of specific animal model for cutaneous diabetic wound healing, we have used common model of wound healing (excision wound model in animals having diabetes (by administration of alloxan monohydrate 120 mg/kg i.p.. Statistics Analysis: Data were analyzed by using one-way ANOVA, followed by Tukey′s post hoc tests, using the Graph Pad Software (5.0 demo version, and P value <0.05 was considered to be significant. Results and Conclusion : Rats treated with 200 mg/kg/day of P. marsupium heart wood extract had high rate of wound contraction, significantly decreased epithelization period, and significant increase in dry weight, wet weight, and hydroxyproline content of the granulation tissue when compared with the diabetic control and normal control groups. Wound contraction together with increased tensile strength and hydroxyproline content support the use of P. marsupium heart wood extract in the management of wound healing in normal and diabetic rats.

  5. Remnant B-cell-stimulative and anti-oxidative effects of Persea americana fruit extract studied in rats introduced into streptozotocin - induced hyperglycaemic state.

    Science.gov (United States)

    Rao, U S Mahadeva; Adinew, Bizuneh

    2011-01-01

    Insulin-stimulative and anti-oxidative effects of Persea americana fruit extract were evaluated using streptozotocin (STZ). Ethanol extract of P. americana in the concentration of 300 mg/kg body weight/rat /day was orally administered to rats introduced into STZ-induced hyperglycaemic state for a period of 30 days. After the treatment with avocado fruit extract, the elevated levels of blood glucose, glycosylated haemoglobin, blood urea and serum creatinine seen in the hyperglycaemic rats, reverted back to near normal. Similarly, significantly decreased plasma insulin and haemoglobin levels went back to near normal after the treatment, suggesting the insulin-stimulative effect of P. americana fruit. Determination of thiobarbituric acid reactive substances (TBARS), hydroperoxides and both enzymatic and non-enzymatic antioxidants, confirmed the anti-oxidative potential of avocado fruit extract which, in turn, might be responsible for its hypoglycaemic potential. Changes in activities of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) seen in the control and experimental rats, revealed the tissue-protective nature of Persea americana fruits, while all of the analysed biochemical parameters were comparable to those obtained with gliclazide as a standard reference drug.

  6. Proteomic Study of Retinal Proteins Associated with Transcorneal Electric Stimulation in Rats

    Directory of Open Access Journals (Sweden)

    Takashi Kanamoto

    2015-01-01

    Full Text Available Background. To investigate how transcorneal electric stimulation (TES affects the retina, by identifying those proteins up- and downregulated by transcorneal electric stimulation (TES in the retina of rats. Methods. Adult Wistar rats received TES on the left eyes at different electrical currents while the right eyes received no treatment and served as controls. After TES, the eye was enucleated and the retina was isolated. The retinas were analyzed by proteomics. Results. Proteomics showed that twenty-five proteins were upregulated by TES. The identified proteins included cellular signaling proteins, proteins associated with neuronal transmission, metabolic proteins, immunological factors, and structural proteins. Conclusions. TES induced changes in expression of various functional proteins in the retina.

  7. INTERLEUKIN 10 INHIBITS THE RAT VSMC PROLIFERATION AND COLLAGEN SECRETION STIMULATED BY ANGIOTENSIN Ⅱ

    Institute of Scientific and Technical Information of China (English)

    夏春芳; 霍勇; 尹航; 朱国英; 唐朝枢

    2001-01-01

    Objective. To study the effect of interleukin 10 (IL-10) on the angiotensin Ⅱ(AngⅡ) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of rat, 3H-thymine (3H-TdR) and 3H-proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively. Results. IL-10 (10-8 -10-10g/ml) inhibited the increase of 3H-TdR and 3H-proline incorporation as wellas FAK activity, which was induced by 10-Tmol/L AngⅡ (P 0.05). Conclusion. IL-10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngⅡ.

  8. [Topographic aspects of visual evoked potentials recorded after flash-pattern stimulation in normal subjects].

    Science.gov (United States)

    Samson-Dollfus, D; Parain, D; Menard, J F; Layet, A; Nehili, F; Dreano, E

    1986-02-01

    Visual evoked responses have been recorded on 14 leads placed on the scalp. They were localised on the central, parietal, temporal and occipital regions. The common reference was linked-ears. The stimulus consisted of a flash pattern. The size of the pattern and of each square was respectively of 20 degrees and 30 min. The stimulation of the total visual field had evoked two families of curves. One of these types of curves was posterior (occipital, temporal and parietal) and consisted in a positive, negative, positive wave (100, 136, 200 msec on average) and the second type was localised on the central leads and much more rhythmic than the posterior response. The initial complex (negative, positive, negative, positive: 70, 92, 120, 178 msec) was followed by a slow after-discharge. The half-field stimulation evoked a P100 component on the contralateral posterior leads, but this P100 was less prominent on the ipsilateral posterior leads. The modifications were particularly evident at the level of the temporal posterior electrodes. This P100 component was the only wave to be modified by half-field visual stimulation. The posterior N136 and P200 wave and all the rhythmic central response were exactly the same with half or total visual field stimulation. The results have obviously shown that the different waves of the visual evoked responses are not coming from the same sources. The interpretation of multichannel evoked recordings was therefore very difficult.

  9. Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion

    OpenAIRE

    Liu, Ai-Fen; Zhao, Feng-bo; Wang, Jing; Lu, Yi-Fan; Tian, Jian; Zhao, Yin; Gao, Yan; Hu, Xia-jun; LIU, XIAO-YAN; Tan, Jie; Tian, Yun-li; Shi, Jing

    2016-01-01

    Background Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. Methods The I/R-related injury was modele...

  10. Stimulation of DNA and Collagen Synthesis by Autologous Growth Factor in Cultured Fetal Rat Calvaria

    Science.gov (United States)

    Canalis, Ernesto; Peck, William A.; Raisz, Lawrence G.

    1980-11-01

    Conditioned medium derived from organ or cell cultures prepared from 19- to 21-day fetal rat calvaria stimulated the incorporation of [3H]proline into collagen and of [3H]thymidine into DNA in organ cultures of the same tissue. Addition of cortisol enhanced the effect on collagen but not on DNA synthesis. These effects appeared to be due to a nondialyzable and heat-stable growth factor.

  11. FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE SPINAL CORD DURING SENSORY STIMULATION IN DIABETIC RATS

    Science.gov (United States)

    Malisza, Krisztina L.; Jones, Cheryl; Gruwel, Marco L.H.; Foreman, Derek; Fernyhough, Paul; Calcutt, Nigel A.

    2009-01-01

    Purpose To determine if differences exist between control and diabetic rats in functional MRI activity of the spinal cord and if fMRI can provide a means of early detection of diabetic neuropathy. Materials and Methods fMRI of the spinal cord, using noxious electrical stimulation (15 V (~8 mA), 0.3 ms, 3 Hz) of the hind paw, was performed in groups of control and streptozotocin (STZ)-induced type 1 diabetic rats. Results Diabetic rats were lighter, hyperglycemic and had lower blood pH than controls. FMRI activity at the lumbar enlargement of the spinal cord was identified in the dorsal horn ipsilateral to stimulus of all animals. Signal intensity changes across the lumbar spinal cord during periods of activity were not significantly different between control and diabetic rats, with a trend towards greater signal changes in controls. When specific regions of the spinal cord were analyzed, control rats exhibited significantly increased BOLD fMRI activity in both ipsilateral and contralateral dorsal horn compared to diabetic rats. Conclusion The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest that BOLD fMRI may be useful in early detection of diabetic neuropathy. PMID:19629995

  12. The impact of serotonergic stimulation on reelin and glutamate decarboxylase gene expression in adult female rats.

    Science.gov (United States)

    Lakatosova, S; Celec, P; Schmidtova, E; Kubranska, A; Durdiakova, J; Ostatnikova, D

    2011-01-01

    Reelin plays an important role in the regulation of synaptic plasticity in adulthood. Administration of 5-metoxytryptamine (5MT), an agonist of serotonin receptors, during natal and neonatal periods results in decreased reelin expression. In adulthood, reelin is expressed by GABAergic neurons. The purpose of this study was to reveal the effect of elevated serotonergic stimulation on the expression of reelin and glutamate decarboxylase (GAD1) in adulthood as well as on depressive behavior and spatial cognitive abilities in adult female rats. Rats were injected with 5MT. A forced swimming test was used for evaluation of the depressive behavior and Morris water maze test was used for evaluation of spatial cognition. Brains were used for measuring the expression of reelin and GAD1. We found a significant decrease in reelin expression in the cerebellum and prefrontal cortex of 5MT-treated rats. GAD1 expression was decreased in the cerebellum of 5MT-treated rats. 5MT-treated rats reached a lower immobility score in the forced swimming test. The Morris water maze test did not reveal any significant differences. We have shown that administration of serotonin receptor agonist resulted in a decreased RELN and GAD1 expression in the cerebellum of adult female rats. We propose that this phenomenon might be relevant in the pathogenesis of autism (Fig. 3, Ref. 38). Full Text in free PDF www.bmj.sk.

  13. Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

    Science.gov (United States)

    Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

    2004-08-01

    Epidemiological studies have reported that elevated levels of particulate air pollution in urban communities are associated with increases in attacks of asthma based on evidence from hospital admissions and emergency department visits. Principal pathologic features of chronic airway diseases, like asthma, are airway inflammation and mucous hypersecretion with excessive amounts of luminal mucus and increased numbers of mucus-secreting cells in regions of the respiratory tract that normally have few or no mucous cells (ie, mucous cell metaplasia). The overall goal of the present project was to understand the adverse effects of urban air fine particulate matter (PM2.5; aerodynamic diameter)* on normal airways and airways compromised with airway inflammation and excess mucus. Our project was specifically designed to (1) examine the chemical and physical characteristics of PM2.5 and other airborne pollutants in the outdoor air of a local Detroit community with a high incidence of childhood asthma; (2) determine the effects of this community-based PM2.5 on the airway epithelium in normal rats and rats compromised with preexisting hypersecretory airway diseases (ie, animal models of human allergic airway disease--asthma and chronic bronchitis); and (3) identify the chemical or physical components of PM2.5 that are responsible for PM2.5 -induced airway inflammation and epithelial alterations in these animal models. Two animal models of airway disease were used to examine the effects of PM2.5 exposure on preexisting hypersecretory airways: neutrophilic airway inflammation induced by endotoxin challenge in F344 rats and eosinophilic airway inflammation induced by ovalbumin (OVA) challenge in BN rats. A mobile air monitoring and exposure laboratory equipped with inhalation exposure chambers for animal toxicology studies, air pollution monitors, and particulate collection devices was used in this investigation. The mobile laboratory was parked in a community in southwestern

  14. The effects induced by swimming training on rats submitted to normal and hypercaloric diets

    Directory of Open Access Journals (Sweden)

    Alice Cristina Antonio dos Santos

    2015-08-01

    Full Text Available The main aim of the present study was to analyse the effects induced by six weeks of swimming periodized training (SPT on the aerobic capacity (AC and body weight (BW, on rats fed with either normal or hypercaloric diets. Twenty-four Wistar rats (90 days old were divided in two groups: Normocaloric (NG, n = 12 and Hypercaloric (HG, n = 12. The rats were fed with respective diets (NG or HG for eight weeks and then underwent SPT for six weeks. Before (pre and after (post the SPT, the animals were submitted to an AC determination, using a ”Chassain Test” . There was no significant changes to AC in the HG group (pre = 5.59 ± 4.56% BW vs. post = 4.45 ± 1.66% BW, but in the NG group it increased significantly (pre = 3.95 ± 2.42% BW vs. post = 4.48 ± 1.18% BW.

  15. Electrical stimulation modulates injury potentials in rats after spinal cord injury*

    Institute of Scientific and Technical Information of China (English)

    Guanghao Zhang; Xiaolin Huo; Aihua Wang; Changzhe Wu; Cheng Zhang; Jinzhu Bai

    2013-01-01

    An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as wel as injury current, can be modulated by direct current field stimulation;however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around-70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon il ustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cel membrane and the reduction of cation influx.

  16. Electrical stimulation modulates injury potentials in rats after spinal cord injury.

    Science.gov (United States)

    Zhang, Guanghao; Huo, Xiaolin; Wang, Aihua; Wu, Changzhe; Zhang, Cheng; Bai, Jinzhu

    2013-09-25

    An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around -70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.

  17. Endotoxin-stimulated Rat Hepatic Stellate Cells Induce Autophagy in Hepatocytes as a Survival Mechanism.

    Science.gov (United States)

    Dangi, Anil; Huang, Chao; Tandon, Ashish; Stolz, Donna; Wu, Tong; Gandhi, Chandrashekhar R

    2016-01-01

    Bacterial lipopolysaccharide (LPS)-stimulated hepatic stellate cells (HSCs) produce many cytokines including IFNβ, TNFα, and IL6, strongly inhibit DNA synthesis, but induce apoptosis of a small number of hepatocytes. In vivo administration of LPS (up to 10 mg/mL) causes modest inflammation and weight loss in rats but not mortality. We determined whether LPS-stimulated HSCs instigate mechanisms of hepatocyte survival. Rats received 10 mg/kg LPS (i.p.) and determinations were made at 6 h. In vitro, HSCs were treated with 100 ng/mL LPS till 24 h. The medium was transferred to hepatocytes, and determinations were made at 0-12 h. Controls were HSC-conditioned medium or medium-containing LPS. LPS treatment of rats caused autophagy in hepatocytes, a physiological process for clearance of undesirable material including injured or damaged organelles. This was accompanied by activation of c-Jun NH2 terminal kinase (JNK) and apoptosis of ~4-5% of hepatocytes. In vitro, LPS-conditioned HSC medium (LPS/HSC) induced autophagy in hepatocytes but apoptosis of only ~10% of hepatocytes. While LPS/HSC stimulated activation of JNK (associated with cell death), it also activated NFkB and ERK1/2 (associated with cell survival). LPS-stimulated HSCs produced IFNβ, and LPS/HSC-induced autophagy in hepatocytes and their apoptosis were significantly inhibited by anti-IFNβ antibody. Blockade of autophagy, on the other hand, strongly augmented hepatocyte apoptosis. While LPS-stimulated HSCs cause apoptosis of a subpopulation of hepatocytes by producing IFNβ, they also induce cell survival mechanisms, which may be of critical importance in resistance to liver injury during endotoxemia.

  18. The Anticonvulsant Effect of Transcutaneous Auricular Vagus Nerve Stimulation is Associated with Balancing the Autonomic Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Wei He

    2016-11-01

    Full Text Available Objective: The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.

  19. Medulla Oblongata Mechanism of Inhibitory Effect of Thermal Stimulation to Nociceptive Colorectal Distention in Rats

    Institute of Scientific and Technical Information of China (English)

    Liang Li; Pei-Jing Rong; Xin-Yan Gao; Hui Ben; Hong Cai; Bing Zhu

    2016-01-01

    Objective: To discuss mechanism of moxibustion (thermal stimulation) effect and best moxibustion stimulus parameter. Methods: Experiments were performed on 48 male Sprague-Dawley rats. Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in Subnucleus Reticularis Dorsalis (SRD). Visceral-intrusive stimulation is done by colorectal distension. Thermal stimulation with different temperature (40°C, 42°C, 44°C, 46°C, 48°C, 50°C, 52°C) and different stimulus area (diameter of circle:1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0cm) was applied around RN12 during nociceptive colorectal distension. Results: SRD neurons could be activated by visceral stimulation within noxious range. Under low temperature of stimulus, especially under 45°C of pain threshold to ordinary people, visceral nociceptive afferent facilitated thermal stimulus from the body surface. While after thermal stimulation reached a harmful degree, the thermal stimulus will inhibit visceral nociceptive afferent. Moreover, statistics show that the higher the temperature is, the smaller the size of stimulation area is needed, and they correlate with each other negatively. Conclusion: Visceral nociception could be inhibited by somatic thermal stimulation with specific parameter at medulla level. According to our finding, best thermal stimulation temperature is around 48°C and the best size of stimulation area is around 3.14-7.07cm2 (with 2.0-3.0cm diameter).

  20. Observation of two distinct spatial-temporal BOLD clusters during sensory stimulation in rats.

    Science.gov (United States)

    Goelman, Gadi; Pelled, Galit; Dodd, Steve; Koretsky, Alan

    2007-02-01

    Neuronal activity evokes changes in local CBF and CBV, whose spatial differences are not fully known. We use the Radial Correlation Contrast (RCC) analysis method with high spatial resolution 100 x 100 x 1000 microm3 data collected with an 11.7 T magnet to differentiate two spatial-temporal BOLD clusters during sensory rat forepaw stimulation and hypothesize that each corresponds to either the CBF or the CBV processes. One cluster, obtained during the time segment of stimulation onset, is characterized by a high positive BOLD signal whereas the other, obtained during the simulation decline time segment, is characterized by a lower positive signal and strong post stimulus undershoot. The average volume of stimulation onset clusters is embedded in the stimulation decline clusters with the latter significantly larger and shifted towards deeper cortical layers. Comparison of amplitude-RCC and cross-correlation analyses performed on equivalent time segments (30 s, 40 images) revealed no differences in cluster size or location, demonstrating that temporal locality is more important than spatial locality in distinguishing between stimulation onset and stimulation decline clusters. We hypothesize that clusters characterized by stimulation onset are highly weighted by local changes in CBF whereas clusters characterized by stimulation decline are more CBV weighted. Moreover, the data suggest that the locations of the highest CBF changes are distinct from the locations of the highest CBV changes. While the former located within stimulation decline clusters and its weight is gradually reduced towards cluster's periphery (mainly ventrally), the highest changes in CBV occur in the cluster's periphery with only modest changes towards its center.

  1. Effect of E.globulus upon Candida colonization in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohammad Bokaeian

    2012-02-01

    Full Text Available Background: The leaves of Eucalyptus globulus (eucalyptus are used for treatment of diabetes mellitus in traditional medicine. The aim of present study is to evaluate the effects of eucalyptus in treatment of systemic infection with Candida albicans in normal and streptozotocin-induced diabetic rats. Materials and Method: Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected and randomly divided into six groups (n=10: I. normal control, II. control+C. albicans, III. control+eucalyptus+C. albicans, IV. Diabetic control, V. diabetic+C. albicans, VI. diabetic+eucalyptus+C. albicans. Experimental diabetes was induced in IV-VI groups after a single intraperitoneal injection of streptozotocin (60 mg/kg body weight and eucalyptus was added to the diet (62.5 g/kg and drinking water (2.5 g/L of III and VI groups for 3 weeks. The II, III, V, and VI groups were inoculated with C. albicans in seventh day using intraperitoneal injection of C. albicans. At the end of 23 days experiment, fasted rats were killed by cervical decapitation. Blood was collected from neck vein for estimation of glucose. C. albicans concentrations were estimated in liver and kidneys using serial dilution culture of tissue homogenates. Results: Eucalyptus administration significantly improved the hyperglycemia, polydipsia, polyphagia, and it also compensated weight loss of diabetic rats (p=0.05. Moreover, eucalyptus caused a significant reduction in C. albicans concentration in liver and kidney homogenates (p=0.04. Conclusion: The results revealed that eucalyptus improves Candidia infection in normal and diabetic rats

  2. Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.

    Science.gov (United States)

    Gauthaman, K; Adaikan, P G; Prasad, R N V

    2002-08-09

    Tribulus terrestris (TT) has long been used in the traditional Chinese and Indian systems of medicine for the treatment of various ailments and is popularly claimed to improve sexual functions in man. Sexual behaviour and intracavernous pressure (ICP) were studied in both normal and castrated rats to further understand the role of TT containing protodioscin (PTN) as an aphrodisiac. Adult Sprague-Dawley rats were divided into five groups of 8 each that included distilled water treated (normal and castrated), testosterone treated (normal and castrated, 10 mg/kg body weight, subcutaneously, bi-weekly) and TT treated (castrated, 5 mg/kg body weight, orally once daily). Decreases in body weight, prostate weight and ICP were observed among the castrated groups of rats compared to the intact group. There was an overall reduction in the sexual behaviour parameters in the castrated groups of rats as reflected by decrease in mount and intromission frequencies (MF and IF) and increase in mount, intromission, ejaculation latencies (ML, IL, EL) as well as post-ejaculatory interval (PEI). Compared to the castrated control, treatment of castrated rats (with either testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant. There was also a mild to moderate improvement of the sexual behaviour parameters as evidenced by increase in MF and IF; decrease in ML, IL and PEI. These results were statistically significant. It is concluded that TT extract appears to possess aphrodisiac activity probably due to androgen increasing property of TT (observed in our earlier study on primates).

  3. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

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    Dinesh Babu Jestadi

    2014-01-01

    Full Text Available The present study evaluates the effects of short term (15 days exposure of low dose (300 μg kg−1 of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine on antioxidant status and markers of liver and kidney damage in normal (nondiabetic and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.

  4. High Frequency Electrical Stimulation of Lateral Habenula Reduces Voluntary Ethanol Consumption in Rats

    Science.gov (United States)

    Li, Jing; Zuo, Wanhong; Fu, Rao; Xie, Guiqin; Kaur, Amandeep; Bekker, Alex

    2016-01-01

    Background: Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanol-drinking behavior in rats. Methods: We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb. Results: c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior. Conclusions: Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics. PMID:27234303

  5. Neurogenesis in the dentate gyrus of the rat hippocampus enhanced by tickling stimulation with positive emotion.

    Science.gov (United States)

    Yamamuro, Takuya; Senzaki, Kouji; Iwamoto, Satomi; Nakagawa, Yoshimi; Hayashi, Takashi; Hori, Miyo; Sakamoto, Shigeko; Murakami, Kazuo; Shiga, Takashi; Urayama, Osamu

    2010-12-01

    Hippocampal neurogenesis is influenced by many factors. In this study, we examined the effect of tactile stimulation (tickling), which induced positive emotion, on neurogenesis in the dentate gyrus (DG) of the hippocampus. Four week-old rats were tickled for 5 min/day on 5 consecutive days and received 5-bromo-2'-deoxyuridine (BrdU) administration for 4 days from the second tickling day. Then they were allowed to survive for 18 h or 3 weeks after the end of BrdU treatment. Neurogenesis in the DG was compared between the tickled and untickled rats by using immunohistochemistry with anti-BrdU antibody. The result showed that the number of BrdU- and NeuN (neural cell marker)-double positive neurons on 18h as well as 3 weeks of the survival periods was significantly increased in the tickled group as compared with the untickled group. The expression of mRNA of brain-derived neurotrophic factor (BDNF) in the hippocampus of the tickled rats was not altered when compared with the control rats. In conclusion, tickling stimulation which induces positive emotion may affect the generation and survival of new neurons of the DG through the BDNF-independent pathway.

  6. Tail nerve electrical stimulation induces body weight-supported stepping in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-Xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-03-30

    Walking or stepping has been considered the result from the activation of the central pattern generator (CPG). In most patients with spinal cord injury (SCI) the CPG is undamaged. To date, there are no noninvasive approaches for activating the CPG. Recently we developed a noninvasive technique, tail nerve electrical stimulation (TANES), which can induce positive hind limb movement of SCI rats. The purpose of this study is to introduce the novel technique and examine the effect of TANES on CPG activation. A 25 mm contusion injury was produced at spinal cord T10 of female, adult Long-Evans rats by using the NYU impactor device. Rats received TANES ( approximately 40 mA at 4 kHz) 7 weeks after injury. During TANES all injured rats demonstrated active body weight-supported stepping of hind limbs with left-right alternation and occasional front-hind coordination, resulting in significant, temporary increase in BBB scores (pelectrical stimulation. Therefore the TANES may have considerable potential for achieving improvement of functional recovery in animal models and a similar method may be suggested for human study. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

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    Ebaid Hossam

    2011-12-01

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

  8. Long-term prolactin exposure differentially stimulated the transcellular and solvent drag-induced calcium transport in the duodenum of ovariectomized rats.

    Science.gov (United States)

    Tudpor, Kukiat; Charoenphandhu, Narattaphol; Saengamnart, Wasana; Krishnamra, Nateetip

    2005-12-01

    Prolactin, having been shown to stimulate transcellular active and solvent drag-induced calcium transport in the duodenum of female rats, was postulated to improve duodenal calcium transport in estrogen-deficient rats. The aim of the present study was, therefore, to demonstrate the effects of long-term prolactin exposure produced by anterior pituitary (AP) transplantation on the duodenal calcium transport in young (9-week-old) and adult (22-week-old) ovariectomized rats. We found that ovariectomy did not alter the transcellular active duodenal calcium transport in young and adult rats fed normal calcium diet (1.0% w/w Ca) but decreased the solvent drag-induced duodenal calcium transport from 75.50 +/- 10.12 to 55.75 +/- 4.77 nmol.hr(-1).cm(-2) (P calcium transport in young and adult AP-grafted ovariectomized rats fed with normal calcium diet by more than 2-fold from 7.56 +/- 0.79 to 16.54 +/- 2.05 (P calcium transport in young rats was enhanced by prolactin from 95.51 +/- 10.64 to 163.20 +/- 18.03 nmol.hr(-1).cm(-2) (P calcium supplement has been widely used to improve calcium balance in estrogen-deficient animals, the effect of a high-calcium diet (2.0% w/w Ca) was also investigated. The results showed that stimulatory action of long-term prolactin on the transcellular active duodenal calcium transport in both young and adult rats was diminished after being fed a high-calcium diet. The same diet also abolished prolactin-enhanced solvent drag-induced duodenal calcium transport in young and further decreased that in adult AP-grafted ovariectomized rats. We concluded that the solvent drag-induced duodenal calcium transport in adult rats was decreased after ovariectomy. Long-term prolactin exposure stimulated the transcellular active duodenal calcium transport in both young and adult rats whereas enhancing the solvent drag-induced duodenal calcium transport only in young rats. Effects of prolactin were abolished by a high-calcium diet.

  9. Stimulation of midbrain dopaminergic structures modifies firing rates of rat lateral habenula neurons.

    Directory of Open Access Journals (Sweden)

    Xuefeng Shen

    Full Text Available Ventral tegmental area (VTA and substantia nigra pars compacta (SNpc are midbrain structures known to be involved in mediating reward in rodents. Lateral habenula (LHb is considered as a negative reward source and it is reported that stimulation of the LHb rapidly induces inhibition of firing in midbrain dopamine neurons. Interestingly, the phasic fall in LHb neuronal activity may follow the excitation of dopamine neurons in response to reward-predicting stimuli. The VTA and SNpc give rise to dopaminergic projections that innervate the LHb, which is also known to be involved in processing painful stimuli. But it's unclear what physiological effects these inputs have on habenular function. In this study we distinguished the LHb pain-activated neurons of the Wistar rats and assessed their electrophysiological responsiveness to the stimulation of the VTA and SNpc with either single-pulse stimulation (300 µA, 0.5 Hz or tetanic stimulation (80 µA, 25 Hz. Single-pulse stimulation that was delivered to either midbrain structure triggered transient inhibition of firing of ∼90% of the LHb pain-activated neurons. However, tetanic stimulation of the VTA tended to evoke an elevation in neuronal firing rate. We conclude that LHb pain-activated neurons can receive diverse reward-related signals originating from midbrain dopaminergic structures, and thus participate in the regulation of the brain reward system via both positive and negative feedback mechanisms.

  10. Uterine contractility and blood flow are reflexively regulated by cutaneous afferent stimulation in anesthetized rats.

    Science.gov (United States)

    Hotta, H; Uchida, S; Shimura, M; Suzuki, H

    1999-01-15

    The effects of cutaneous mechanical afferent stimulation of various skin areas on uterine contractility and blood flow were examined in anesthetized non-pregnant rats. The contractility of the uterus was measured by the balloon method in the uterus. The uterine blood flow was measured by laser Doppler flowmetry. Noxious pinching stimulation of the perineum for 1 min induced an abrupt contraction of the uterus during stimulation. Pinching of a hindpaw or perineum and innocuous brushing of the perineum for 1 min increased uterine blood flow. Stimulation of other skin areas produced no changes in uterine contractility or blood flow. Most uterine responses were abolished by severance of the pelvic nerves, which innervated the uterus. The activity of pelvic parasympathetic efferent nerves to the uterus increased following perineal pinching. All these cutaneous stimulation-induced responses of uterine contractility, blood flow and pelvic efferent nerve activity still existed, and were even augmented, after acute spinalization. These results indicate that cutaneous mechanical sensory stimulation can regulate uterine contractility and blood flow by a segmental spinal reflex mechanism via uterine parasympathetic efferent nerves.

  11. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

    DEFF Research Database (Denmark)

    Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.

    2013-01-01

    High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased......, iron isomaltoside 1000 (IIM) and ferric carboxymaltose (FCM), on plasma levels of FGF23 and phosphate was examined in normal and uremic iron repleted rats....

  12. Enhanced synaptic responses in the piriform cortex associated with sexual stimulation in the male rat.

    Science.gov (United States)

    Pfaus, J G; Tse, T L M; Werk, C M; Chanda, M L; Leblonde, A; Harbour, V L; Chapman, C A

    2009-12-29

    Male rats that copulate to ejaculation with female rats bearing an odor show a learned preference to ejaculate selectively with females that bear the odor. This conditioned ejaculatory preference reflects an association between the odor and the reward state induced by ejaculation. Although little is known about the neuronal mechanisms that mediate this form of learning, convergence of genitosensory and olfactory inputs occurs in both hypothalamic and cortical regions, notably within primary olfactory (piriform) cortex, which may be involved in the encoding or storage of the association. The present study contrasted the ability of genital investigations, mounts, intromissions, ejaculations, and a sexually conditioned olfactory stimulus, to enhance evoked synaptic field potentials in the piriform cortex. Rats in the Paired group underwent conditioning trials in which they copulated with sexually receptive females bearing an almond odor. Rats in the Unpaired control group copulated with receptive females bearing no odor. Responses in the piriform cortex evoked by electrical stimulation of the olfactory bulb were recorded in male rats as they engaged in different aspects of sexual behavior, and were also recorded after conditioning, during exposure to cotton swabs bearing the almond odor. The monosynaptic component of responses was increased during intromission and ejaculation, and the late component of responses was increased during anogenital sniffing and mounting (with or without intromission). However, no differences in the amplitudes of evoked responses were found between the Paired and Unpaired groups, and no differences in synaptic responses were found during presentation of the odor after conditioning. These data indicate that short-term alterations in synaptic responsiveness occur in piriform cortex as a function of sexual stimulation in the male rat, but that responses are not significantly altered by a conditioned odor.

  13. Anodal transcranial direct current stimulation relieves the unilateral bias of a rat model of Parkinson's disease.

    Science.gov (United States)

    Li, Yiyan; Tian, Xulong; Qian, Long; Yu, Xuehong; Jiang, Weiwei

    2011-01-01

    The unilaterally lesioned rat model of Parkinson's disease which fails to orient to the food stimuli presented on the contralateral side of its preferential side of body could be induced by the injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). We employed transcranial direct current stimulation (tDCS, current intensity: 80 μA, and 40 μA; anodal electrode area: 3.14 mm(2); stimulation time: 30 minutes) over the M1 area to relieve the ipsilateral bias in the rat model. A corridor test was set to count the ipsilateral bias of the rats. In this experiment, 30 Sprague-Dawley rats (80 μA: n = 8, 40 μA: n = 8, sham: n = 7, healthy control: n = 7) were chosen for the corridor test and the tDCS session. The lesioned rats exhibited increased ipsilateral bias 4 weeks after the lesion surgery (P < 0.01), and the anodal tDCS with the active electrode on the lesioned side relieved the ipsilateral bias significantly (P < 0.01) immediately after the surgery and the improvement lasted for nearly 1 day. The rats in the group of 80 μA exhibited more significant changes than the 40 μA group after one day. After all the experiments, the histological process showed no neurotrauma led by the tDCS. In conclusion, the modulatory function of the cortical excitability of the tDCS may awaken the compensatory mechanisms and the response mechanisms which modulate the loss of the brain function. Further studies should be done to provide more evidence about the assumption.

  14. Frequency-dependent entrainment of neocortical slow oscillation to repeated optogenetic stimulation in the anesthetized rat.

    Science.gov (United States)

    Kuki, Toshinobu; Ohshiro, Tomokazu; Ito, Shin; Ji, Zhi-Gang; Fukazawa, Yugo; Matsuzaka, Yoshiya; Yawo, Hiromu; Mushiake, Hajime

    2013-01-01

    Local field potential (LFP) slow oscillation (entrained to repeated external sensory stimuli. To better understand the neural mechanism underlying slow-oscillation generation and its entrainment to external stimuli, we delivered optical stimulation to the cortex of anesthetized rats that exogenously expressed the light-sensitive cation channel channelrhodopsin-2 (ChR2) and simultaneously monitored LFPs across cortical layers. We found that the LFPs could be effectively entrained to repeated optical stimulation at 1Hz in deep layers. A stimulus-triggered current-source density (CSD) analysis showed that the evoked oscillation had the same depth and temporal profile as the slow oscillations, indicating that both oscillations have the same neural mechanism. Optical stimulation primarily induced the transition from the cortical up to down state. These results suggest that the anesthetized rat cortex has an intrinsic mechanism that leads to oscillation near 1Hz; effective entrainment to the 1Hz stimulation reflects the resonated state of the cortex to that stimulus. Our study is the first to demonstrate optogenetic manipulation of cortical slow oscillation and provides a mechanistic explanation for slow-oscillation entrainment.

  15. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... documented an initial 2.6-fold increase in neurogenesis following a clinical relevant schedule of ECS, a treatment also rescuing depression-like behavior in rats. However, these results gave no demonstration of the longevity of newly generated neurons. The present study is a direct continuation...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd...

  16. RAT EXOCRINE PANCREATIC SECRETION BY VAGAL STIMULATION OCCURS VIA MULTIPLE MEDIATORS

    Institute of Scientific and Technical Information of China (English)

    何晓东; MTimmthyNelson; HaileTDebas

    1996-01-01

    The vagus is a mixed nerve containing cholinerrgic and non-cholinergie neurons. Vagal fibers interact with peptidergic neurons of the enteric nervous system which stain immunohistcchemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin releasing peptide. The contribution of these pepticdergic neurons in the pancreatic response to vagal stimulation is unknown. We tested the effect of specific inhibitor of these stimulants against vagally mediated exocrine secretion in rats. The response to vagal stimulation was blocked significantly hy each of the following:the ganglionic blocker hexmethoninm (100% inhibition); the muscarinic, cholinergic blocker atropine (85%inhibition) ; the specific cholaeystokinln-A receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). This observation is consistent with the hypothesis that potentiating interactions among several agonisrs mediate the vagal response. Our study, however, dose not exclude acetylehollne as the final commom mediator.

  17. Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats

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    Costanzo Francesco S

    2006-02-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. Results We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Conclusion Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.

  18. Differences in expression of retinal proteins between diabetic and normal rats

    Institute of Scientific and Technical Information of China (English)

    Shang-Qing Liu; Jian Kang; Cheng-Jun Li; En-Jie Tang; Bin Wen; Rong Cai; Hui-Jun Yang

    2007-01-01

    AIM: To compare and identify the differences in expression of retinal proteins between normal and diabetic rats, and to analyze the molecular pathogenetic mechanisms of retinal diseases caused by diabetes.METHODS: Changes in protein expression of retinal tissues from diabetic and normal rats were observed using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Some protein spots exhibiting statistically significant variations (P < 0.05) were selected randomly and identified by tandem mass spectrometry and analyzed by bioinformatics.RESULTS: 2-DE showed that the expression was upregulated in 5 retinal proteins, down-regulated in 23retinal proteins, and disappeared in 8 retinal proteins.Eight spots were identified from the 36 spots by tandem mass spectrometry (MS/MS) and analyzed by bioinformatics. Guanylate kinase 1, triosephosphate isomerase 1, ATP synthase subunit d, albumin and dimethylarginine dimethylaminohydrolase 2 played an important role in signal transduction. Triosephosphate isomerase 1, crystallin alpha B, ATP synthase subunit d and peroxiredoxin 6 were involved in energy metabolism of retinal tissues. Guanylate kinase 1 played an important role in photoexcitation of retinal rod photoreceptor cells.Whether crystallin beta A1 plays a role in diabetic retinas is unknown so far.CONCLUSION: There are differences in expression of retinal proteins between diabetic and normal rats.These proteins may be involved in the mechanisms and prognosis of retinal diseases caused by diabetes.

  19. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico)); Rivera, F. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Babinski, E. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Berlanga, E. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Madrazo, M. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Franco-Bourland, R. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico)); Grijalva, I. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  20. Sex differences in the effect of MK-801 on normal and spinal cord injured rats.

    Science.gov (United States)

    Nieto-Sampedro, M; Bailón, C; Rivas, F; Moreno, M T

    1991-01-01

    The induction of functional paraplegia in female rats by contusive spinal cord injury was not prevented by compound MK-801. However, the treatment reduced cavitation around the lesion epicenter to 14 mm3 compared to 17 mm3 in untreated controls t-test, P vaginal frotis. Also, beginning 24 h after MK-801 injection, the proportion of PMN increased 400% in female blood, whereas males maintained control values. Arthritis-like joint inflammation was prominent in the toes of female rats, but males were unaffected. After continued treatment with the drug for 15 days, PMN count in female rats decreased and the animals resumed cycling. However, during this period female rats lost 20% of their weight, whereas males gained 26%. One hour after MK-801 injection large increases in blood pressure occurred in both sexes, returning to normal values 2 h later. Hypothermia does not appear to be a factor in the neuroprotective effect of MK-801, but the drug has a number of potentially dangerous side effects, particularly in female rats. Because polymorphonuclear cells are known sources of oxygen free radicals, neuroprotection by MK-801 treatment ought to be much more efficient in males than in females and the drug should be used in combination with a free-radical scavenger.

  1. Comparison of numbers of interneurons in three thalamic nuclei of normal and epileptic rats.

    Science.gov (United States)

    Cavdar, Safiye; Bay, Hüsniye Hacioğlu; Yildiz, Sercan D; Akakin, Dilek; Sirvanci, Serap; Onat, Filiz

    2014-06-01

    The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of inhibitory neurotransmission in the thalamus. In the present study, we used light-microscopic gamma-aminobutyric acid (GABA) immunocytochemistry to quantify the interneurons in the lateral geniculate (LGN), ventral posteromedial (VPM), and ventral posterolateral (VPL) thalamic nuclei, and compared the values from normal Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS). We found that in both Wistar rats and GAERS, the proportion of interneurons was significantly higher in the LGN than in the VPM and VPL. In the LGN of Wistar rats, 16.4% of the neurons were interneurons and in the GAERS, the value was 15.1%. In the VPM, the proportion of interneurons was 4.2% in Wistar and 14.9% in GAERS; in the VPL the values were 3.7% for Wistar and 11.1% for the GAERS. There was no significant difference between Wistar rats and the GAERS regarding the counts of interneurons in the LGN, whereas the VPM and VPL showed significantly higher counts in GAERS. Comparison of the mean areas of both relay cells and interneuronal profiles showed no significant differences between Wistar rats and GAERS. These findings show that in the VPL and the VPM there are relatively more GABAergic interneurons in GAERS than in Wistar rats. This may represent a compensatory response of the thalamocortical circuitry to the absence seizures or may be related to the production of absence seizures.

  2. Tocotrienols are needed for normal bone calcification in growing female rats.

    Science.gov (United States)

    Norazlina, Mohamed; Ima-Nirwana, Soelaiman; Abul Gapor, Mohd Top; Abdul Kadir Khalid, B

    2002-01-01

    In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.

  3. Aortic depressor nerve stimulation does not impede dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

    Science.gov (United States)

    Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-03-08

    Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY, n=8) rats and spontaneously hypertensive rats (SHR, n=7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4±14.0 vs. 51.6±11.3 arbitrary units in WKY, P = 0.012; and 248.7±33.9 vs. 181.1±16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8±6.6 vs. 81.2±5.4 mmHg in WKY, P=0.004; and 128.6±9.8 vs. 114.7±10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55±0.93 vs. 13.03±1.28 dB/decade in WKY, P = 0.542; and 17.37±1.01 vs. 17.47±1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.

  4. Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats

    NARCIS (Netherlands)

    Kole, MHP; Fuchs, E; Ziemann, U; Paulus, W; Ebert, U

    1999-01-01

    The effects of a single rapid-rate transcranial magnetic stimulation (rTMS) exposure on neurotransmitter binding sites in the rat brain 24 h after the stimulation were examined. Quantification by in vitro-autoradiography showed no differences for H-3-paroxetine binding (5-HT uptake sites) between rT

  5. Dorsal Root Ganglionic Field Stimulation Relieves Spontaneous and Induced Neuropathic Pain in Rats.

    Science.gov (United States)

    Pan, Bin; Yu, Hongwei; Fischer, Gregory J; Kramer, Jeffery M; Hogan, Quinn H

    2016-12-01

    Dorsal root ganglion (DRG) electrical stimulation (ganglionic field stimulation [GFS]) is effective in relieving clinical pain, but its mechanism is unknown. We therefore developed a rat model for GFS to test analgesic effects in the context of neuropathic pain. GFS was applied with a bipolar electrode at L4, using parameters replicating clinical use (20 Hz, 150-μs pulse width, current at 80% of motor threshold). Neuropathic pain was generated by tibial nerve injury (TNI). Pain behavior was monitored by determining the threshold for withdrawal from punctate mechanical stimuli, by identifying hyperalgesic responses to noxious mechanical stimuli, and by hypersensitivity to cold. The affective dimension of pain was measured using conditioned place preference. We found that electrode insertion caused no behavioral evidence of pain and produced no histological evidence of DRG damage. GFS reversed TNI-induced hypersensitivity to cold and mechanical hyperalgesia and allodynia. Allodynia remained diminished 15 minutes after GFS. Conditioned place preference showed that GFS was not rewarding in uninjured control animals but was rewarding in animals subjected to TNI, which reveals analgesic efficacy of GFS for spontaneous pain. We conclude that GFS relieves neuropathic pain in rats. This model may provide a platform for identifying mechanisms and novel applications of GFS. We show that electrical stimulation of the DRG in rats reverses neuropathic pain behavior and provides a rewarding effect to animals with spontaneous neuropathic pain. This confirms analgesic efficacy of DRG stimulation in an animal model, and provides a platform for preclinical exploration. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats

    Science.gov (United States)

    Dimov, Luiz Fabio; Franciosi, Adriano Cardozo; Campos, Ana Carolina Pinheiro; Brunoni, André Russowsky

    2016-01-01

    Transcranial direct current stimulation (tDCS) is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS) on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG) and the dorsal horn of the spinal cord (DHSC) in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1), which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment. PMID:27071073

  7. Hypoglycemic activity of Cassia javanica Linn. in normal and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Urmila C Kumavat

    2012-01-01

    Full Text Available In present work, one of the ornamentals and medicinally less known plant Cassia javanica has been explored for hypoglycemic potential. It aimed to check the hypoglycemic effect of C. javanica leaves on normal and streptozotocin (STZ-induced diabetic rats by acute and sub-acute studies. Prior to the hypoglycemic study, acute oral toxicity testing of drug was performed. Later, the effects of single and multiple doses of test drug were studied using various parameters. Dried powdered leaf material was used as an oral drug. The preliminary phytochemistry of drug was done by standard qualitative tests. Diabetes was induced in rats by single intraperitoneal injection of STZ. Single and multiple doses of test drug (0.5 g/kg body weight/day were given to normal and diabetic rats. The parameters studied were blood glucose, serum cholesterol, serum triglycerides, and serum proteins. The results of test drug were compared with standard hypoglycemic drug-glibenclamide (0.01 g/kg/day. Statistical analysis was done by ′Student′s ′t′ test′ and one way ANOVA test. In preliminary phytochemistry, antidiabetic compounds were detected. Unlike acute, subacute treatment of test drug showed highly significant reduction (37.62% in blood glucose level of diabetic rats in ten days. This effect was considerably good in comparison with standard drug (63.51%. The test drug and standard drug exhibited insignificant change in the abnormal levels of serum metabolites of diabetic rats. Preclinically, C. javanica was proved to be effective hypoglycemic agent.

  8. Hypoglycemic Effects of Achillea Wilhelmsii in Normal and Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    H Sadeghi

    2009-04-01

    Full Text Available ABSTRACT Introduction & Objective: Diabetes mellitus is a syndrome, initially characterized by a loss of glucose homeostasis resulting from defects in Insulin secretion, insulin action both is resulting in impaired metabolism of glucose and other energy yielding fuels as lipids and protein. Several medicinal herbs have been described with hypoglycemic effects. These include: Allium Sativum, Trigonella Foenum, Marus nigra, Ocimum Sanctum, and Astragalus Ovinus. The main purpose of the present study was to determine the effect of Achillea Wilhelmsii C. Koch on blood glucose levels of diabetic rats induced by stereptozotocine (STZ. Materials & Methods: In this experimental research, forty-eight male Wistar rats were divided into two groups: non-diabetic (normal and STZ-induced diabetic mice. Each group was further divided into four groups: control (induced by normal saline and treatment received 100, 200.and 300 mg/kg aqueous- alcoholic extract of Achillea Wilhelmsii C. Koch daily for one month. The blood glucose level was measured and Data were analyzed by t-test and ANOVA. Results: At the end of first month, significant decrease was observed in blood glucose level in diabetic rats which received 100 mg/kg (p<0/001, 200mg/kg(p<0/01, 300mg/kg (p<0/001 of aqueous alcoholic extract of Achillea Wilhelmsii C. Koch in comparison with control groups. The extract had not have any significant effects on the blood glucose level of normal groups except in those which received 300mg/kg of the extract. Conclusion: The results of this study showed that aqueous- alcoholic extract of Achillea Wilhelmsii C. Koch have a significant effect on reducing the blood glucose level of diabetic rats.

  9. Reflex inhibition of normal cramp following electrical stimulation of the muscle tendon.

    Science.gov (United States)

    Khan, Serajul I; Burne, John A

    2007-09-01

    Muscle cramp was induced in one head of the gastrocnemius muscle (GA) in eight of thirteen subjects using maximum voluntary contraction when the muscle was in the shortened position. Cramp in GA was painful, involuntary, and localized. Induction of cramp was indicated by the presence of electromyographic (EMG) activity in one head of GA while the other head remained silent. In all cramping subjects, reflex inhibition of cramp electrical activity was observed following Achilles tendon electrical stimulation and they all reported subjective relief of cramp. Thus muscle cramp can be inhibited by stimulation of tendon afferents in the cramped muscle. When the inhibition of cramp-generated EMG and voluntary EMG was compared at similar mean EMG levels, the area and timing of the two phases of inhibition (I(1), I(2)) did not differ significantly. This strongly suggests that the same reflex pathway was the source of the inhibition in both cases. Thus the cramp-generated EMG is also likely to be driven by spinal synaptic input to the motorneurons. We have found that the muscle conditions that appear necessary to facilitate cramp, a near to maximal contraction of the shortened muscle, are also the conditions that render the inhibition generated by tendon afferents ineffective. When the strength of tendon inhibition in cramping subjects was compared with that in subjects that failed to cramp, it was found to be significantly weaker under the same experimental conditions. It is likely that reduced inhibitory feedback from tendon afferents has an important role in generating cramp.

  10. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    ChunLIANG; Zong-guiWU; JianDING; Jian-feiJIANG; Gao-zhongHUANG; Rong-zengDU; Jun-boGE

    2004-01-01

    AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (ATI) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU·kg·-1·month-1 and fed an atherogenic diet for 4 months to induce experimental atheroma. Then either placebo or losartan 50 kU·kg·-1·d-1 was administered in rats for another 2 months. In vitro, the effect of losartan 0.1-10 μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang Ⅱ-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9,10527±1002 vs 14623±2462, P<0.01). In cultured rat peritoneal macrophages, Ang Ⅱ 0.1 μmol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner (P<0.01). But the AT2receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang Ⅱ bioactivity.

  11. Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Sara Lombardi

    2014-06-01

    Full Text Available Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development.

  12. Growth hormone is secreted by normal breast epithelium upon progesterone stimulation and increases proliferation of stem/progenitor cells.

    Science.gov (United States)

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-06-01

    Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development.

  13. Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats

    Energy Technology Data Exchange (ETDEWEB)

    Balduini, W.; Murphy, S.D.; Costa, L.G. (Univ. of Washington, Seattle (USA))

    1990-05-01

    Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: (1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and (2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of (3H) inositol phosphates in (3H)inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats. Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of (3H)QNB (r2 = 0.627) and, particularly, with (3H)pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%.

  14. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

    Directory of Open Access Journals (Sweden)

    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

  15. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    Science.gov (United States)

    Albaugh, Daniel L.; Salzwedel, Andrew; van den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-09-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action.

  16. Calcium transients in single fibers of low-frequency stimulated fast-twitch muscle of rat.

    Science.gov (United States)

    Carroll, S; Nicotera, P; Pette, D

    1999-12-01

    Ca(2+) transients were investigated in single fibers isolated from rat extensor digitorum longus muscles exposed to chronic low-frequency stimulation for different time periods up to 10 days. Approximately 2.5-fold increases in resting Ca(2+) concentration ([Ca(2+)]) were observed 2 h after stimulation onset and persisted throughout the stimulation period. The elevated [Ca(2+)] levels were in the range characteristic of slow-twitch fibers from soleus muscle. In addition, we noticed a transitory elevation of the integral [Ca(2+)] per pulse with a maximum ( approximately 5-fold) after 1 day. Steep decreases in rate constant of [Ca(2+)] decay could be explained by an immediate impairment of Ca(2+) uptake and, with longer stimulation periods, by an additional loss of cytosolic Ca(2+) binding capacity resulting from a decay in parvalbumin content. A partial recovery of the rate constant of [Ca(2+)] decay in 10-day stimulated muscle could be explained by an increasing mitochondrial contribution to Ca(2+) sequestration.

  17. Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

    Science.gov (United States)

    Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

    2014-04-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. The effect of long-term pulsing electromagnetic field stimulation on experimental osteoporosis of rats.

    Science.gov (United States)

    Mishima, S

    1988-03-01

    The author performed experiments in order to investigate what biological effect on the bone would be produced by long-term pulsing electromagnetic field (PEMF) systemic stimulation. In some of the mature female rats used as experimental animals, bilateral ovariectomy and right sciatic neurectomy were performed in order to make a model osteoporosis. PEMF stimulation was produced by repetitive pulse burst (RPB) waves at a positive amplitude of 25 mV, negative amplitude of 62.5 mV, burst width of 4.2 ms, pulse width of 230 microseconds and 12 Hz, with the magnetic field strength within a cage being set at 3-10 Gauss. PEMF stimulation over 6 months did not produce any effects on the physiologically aged bones. PEMF stimulation also did not produce any effects on losed cortical bone in osteoporotic hindlegs. On the other hand, an increase of bone volume and bone formation activity was observed in the cancellous bone of osteoporotic hindlegs. These findings suggested that PEMF stimulation exerted a preventive effect against bone loss of osteoporotic hindlegs. Furthermore, an observed increase in bone marrow blood flow seemed to be related with this increase of bone volume and bone formation activity.

  19. Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

    Directory of Open Access Journals (Sweden)

    Parag N Gad

    Full Text Available The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

  20. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    Science.gov (United States)

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  1. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    Science.gov (United States)

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Different Kinetics of Puerarin in Plasma of Normal and Depressed Rats After Oral Administration of Chinese Medicine TZ18

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The objective of this study is to quantify the puerarin in rat plasma following oral administration of TZ18 and compare the pharmacokinetics characteristics of puerarin in normal rats with that in depression model rats. A high performance liquid chromatography method was used to quantify the puerarin due to its Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (Maximum coefficient of variation was 5.74% for intra-day and 3.09% for inter-day) over the entire range. The recoveries spectively. The concentration-time curves for both normal rats and depression model rats were fit to a twocompartment model with the first order absorption. The results show significant differences in the main pharmacokinetic parameters of peak time, peak concentration, and the area under the concentration-time curve between the two kinds of rats.

  3. An implantable device for neuropsychiatric rehabilitation by chronic deep brain stimulation in freely moving rats

    Science.gov (United States)

    Wang, Chenguang; Zhang, Fuqiang; Jia, Hong

    2017-01-01

    Successful practice of clinical deep brain stimulation (DBS) calls for basic research on the mechanisms and explorations of new indications in animals. In the article, a new implantable, single-channel, low-power miniature device is proposed, which may transmit pulses chronically into the brain nucleus of freely moving rats. The DBS system consists of an implantable pulse generator (IPG), a bipolar electrode, and an external programmer. The IPG circuit module is assembled as a 20-mm diameter circular board and fixed on a rat’s skull together with an electrode and battery. The rigid electrode may make its fabrication and implantation more easy. The external programmer is designed for bidirectional communication with the IPG by a telecontrol transceiver and adjusts stimulation parameters. A biological validation was performed in which the effects of electrical stimulation in brain nucleus accumbens were detected. The programmed parameters were accurate, implant steady, and power sufficient to allow stimulation for more than 3 months. The larger area of the electrode tip provided a moderate current or charge density and minimized the damage from electrochemistry and pyroelectricity. The rats implanted with the device showed a reduction in morphine-induced conditioned place preference after high-frequency stimulation. In conclusion, the DBS device is based on the criteria of simple technology, minimal invasion, low cost, small in size, light-weight, and wireless controlled. This shows that our DBS device is appropriate and can be used for preclinical studies, indicating its potential utility in the therapy and rehabilitation of neuropsychiatric disorders. PMID:28121810

  4. High Frequency Stimulation of the Pelvic Nerve Inhibits Urinary Voiding in Anesthetized Rats

    Directory of Open Access Journals (Sweden)

    Jonathan J. Crook

    2017-08-01

    Full Text Available Urge Urinary Incontinence: “a sudden and uncontrollable desire to void which is impossible to defer” is extremely common and considered the most bothersome of lower urinary tract conditions. Current treatments rely on pharmacological, neuromodulatory, and neurotoxicological approaches to manage the disorder, by reducing the excitability of the bladder muscle. However, some patients remain refractory to treatment. An alternative approach would be to temporarily suppress activity of the micturition control circuitry at the time of need i.e., urgency. In this study we investigated, in a rat model, the utility of high frequency pelvic nerve stimulation to produce a rapid onset, reversible suppression of voiding. In urethane-anesthetized rats periodic voiding was induced by continuous infusion of saline into the bladder whilst recording bladder pressure and electrical activity from the external urethral sphincter (EUS. High frequency (1–3 kHz, sinusoidal pelvic nerve stimulation initiated at the onset of the sharp rise in bladder pressure signaling an imminent void aborted the detrusor contraction. Urine output was suppressed and tone in the EUS increased. Stimulating the right or left nerve was equally effective. The effect was rapid in onset, reversible, and reproducible and evoked only minimal “off target” side effects on blood pressure, heart rate, respiration, uterine pressure, or rectal pressure. Transient contraction of abdominal wall was observed in some animals. Stimulation applied during the filling phase evoked a small, transient rise in bladder pressure and increased tonic activity in the EUS, but no urine output. Suppression of micturition persisted after section of the contralateral pelvic nerve or after ligation of the nerve distal to the electrode cuff on the ipsilateral side. We conclude that high frequency pelvic nerve stimulation initiated at the onset of an imminent void provides a potential means to control urinary

  5. Iron may induce both DNA synthesis and repair in rat hepatocytes stimulated by EGF/pyruvate

    Energy Technology Data Exchange (ETDEWEB)

    Chenoufi, N.; Loreal, O.; Cariou, S.; Hubert, N.; Lescoat, G. [Univ. Hospital Pontchaillou, Unite de Recherches Hepatologiques, INSERM U 49, Rennes (France); Drenou, B. [Univ. Hospital Pontchaillou, Lab. d`Hematologie et d`Immunologie, Rennes (France); Leroyer, P.; Brissot, P. [Univ. Hospital Pontchaillou, Clinique des Maladies du Foie, Rennes (France)

    1997-03-01

    Background/Aims: Hepatocellular carcinoma develops frequently in the course of genetic hemochromatosis, and a role of iron overload in hepatic carcinogenesis is strongly suggested. Methods: The aim of our study was to investigate the effect of iron exposure on DNA synthesis of adult rat hepatocytes maintained in primary culture stimulated or not by EGF/pyruvate and exposed to iron-citrate complex. Results: In EGF/pyruvate-stimulated cultures, the level of [{sup 3}H] methyl thymidine incorporation was strongly increased as compared to unstimulated cultures. The addition of iron to stimulated cultures increased [{sup 3}H] methyl thymidine incorporation. The mitotic index was also significantly higher at 72 h. However,the number of cells found in the cell layer was not significantly different from iron-citrate free culture. By flow cytometry, no difference in cell ploidy was found between iron-treated and untreated EGF/pyruvate-stimulated cultures. A significant increase in LDH leakage reflecting a toxic effect of iron was found in the cell medium 48 h after cell seeding. In addition, [{sup 3}H] methyl thymidine incorporation in the presence of hydroxyurea was increased in iron-treated compared to untreated cultures. Conclusions: Our results show that DNA synthesis is increased in the presence of iron in rat hepatocyte cultures stimulated by EGF/pyruvate, and they suggest that DNA synthesis is likely to be related both to cell proliferation and to DNA repair. These observations may allow better understanding of the role of iron overload in the development of hepatocellular carcinoma. (au) 61 refs.

  6. Comparative study on pharmacokinetics of Cephradine in diabetic and normal rats

    Institute of Scientific and Technical Information of China (English)

    LIANG Jun; FU Ting; HAN Guo-zhu; LU Li

    2008-01-01

    Objective To study effects of diabetes mellitus (DM) on pharmacokinetics of cephradine (CED) by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats. Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1; rats whose blood glucose was over 16 mmol·L-1 were taken as DM group. The rats were divided into DM group and normal control (CTL) group, which were subdivided into low dose (90 mg·kg-1) and high dose (180 mg·kg-1) subgroups. CED was administered by iv or po routes. Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course. Chromatographic separation was achieved on a Kromasil C18 column (250×4.6 mm ID, 5 μm);mobile phase, consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN (87; 6 : 7 v/v), was delivered at 1.0 mL·min-1; UV detector was set at 261 nm.The peak area ratio of CED to cephalexin (CEX) as internal standard vs concentraion of CED was used to construct calibration curve. 50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph. Results The methodology validation including specificity, precision, accuracy, recovery, limit of quantitation, linearity, stability, etc., showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics. However, in iv experiment, DM group, when compared with CTL group, presented a significantly shortened t1/2β and MRT as well as increased CL, reflected by t1/2β 84-91 vs 116-120 min, MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment, a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found; meanwhile, DM rats suffered from remarkably increased kidney weight (KW) and KW/BW ratio relative to CTL rats

  7. Effects of insulin replacements, inhibitors of angiotensin, and PKCbeta's actions to normalize cardiac gene expression and fuel metabolism in diabetic rats.

    Science.gov (United States)

    Arikawa, Emi; Ma, Ronald C W; Isshiki, Keiji; Luptak, Ivan; He, Zhiheng; Yasuda, Yutaka; Maeno, Yasuhiro; Patti, Mary Elizabeth; Weir, Gordon C; Harris, Robert A; Zammit, Victor A; Tian, Rong; King, George L

    2007-05-01

    High-density oligonucleotide arrays were used to compare gene expression of rat hearts from control, untreated diabetic, and diabetic groups treated with islet cell transplantation (ICT), protein kinase C (PKC)beta inhibitor ruboxistaurin, or ACE inhibitor captopril. Among the 376 genes that were differentially expressed between untreated diabetic and control hearts included key metabolic enzymes that account for the decreased glucose and increased free fatty acid utilization in the diabetic heart. ICT or insulin replacements reversed these gene changes with normalization of hyperglycemia, dyslipidemia, and cardiac PKC activation in diabetic rats. Surprisingly, both ruboxistaurin and ACE inhibitors improved the metabolic gene profile (confirmed by real-time RT-PCR and protein analysis) and ameliorated PKC activity in diabetic hearts without altering circulating metabolites. Functional assessments using Langendorff preparations and (13)C nuclear magnetic resonance spectroscopy showed a 36% decrease in glucose utilization and an impairment in diastolic function in diabetic rat hearts, which were normalized by all three treatments. In cardiomyocytes, PKC inhibition attenuated fatty acid-induced increases in the metabolic genes PDK4 and UCP3 and also prevented fatty acid-mediated inhibition of basal and insulin-stimulated glucose oxidation. Thus, PKCbeta or ACE inhibitors may ameliorate cardiac metabolism and function in diabetes partly by normalization of fuel metabolic gene expression directly in the myocardium.

  8. Stimulant effect of nitric oxide generator and roxatidine on mucin biosynthesis of rat gastric oxyntic mucosa.

    Science.gov (United States)

    Ichikawa, T; Ishihara, K; Kusakabe, T; Kawakami, T; Hotta, K

    1999-01-01

    Although the involvement of nitric oxide (NO) in an increasing gastric mucus metabolism has been reported, information on whether or not its activation is limited to the specific mucus-producing cells is lacking. In this paper, we report the effect of the exogenous NO-donor, isosorbide dinitrate (ISDN), and second-generation histamine H2 receptor antagonist roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]propyl)acetamide hydrochloride) which is demonstrated to accelerate the mucin metabolism mediated by endogenous NO, on the mucin biosynthesis in distinct sites and layers of the rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue of full-thickness and the deep corpus layer, and the antrum of the rat stomach incubated for 5 hr with [3H]glucosamine(GlcN) in vitro. With the addition of ISDN to the culture medium, 3H-labeled mucin in the full-thickness corpus mucosa increased to 124-145% of the control (proxatidine stimulated the mucin biosynthesis in the full-thickness corpus mucosa, but not in the gland mucous cell layer. These results suggest that the stimulation of the mucin biosynthesis mediated by NO is restricted to the surface mucous cells of the rat gastric oxyntic mucosa.

  9. Effects of High-Voltage Electrical Stimulation in Improving the Viability of Musculocutaneous Flaps in Rats.

    Science.gov (United States)

    Neves, Lais Mara Siqueira das; Guirro, Elaine Caldeira de Oliveira; Albuquerque, Fernanda Luiza de Almeida; Marcolino, Alexandre Marcio

    2016-10-01

    The musculocutaneous flap of the transverse rectus abdominis muscle is a technique used for breast reconstruction, and one of the complications of this procedure is tissue necrosis. The objective of the study is to determine the effect of high-voltage electrical stimulation (HVES) in the transverse rectus abdominis muscle flap in rats. Fourteen rats underwent surgery for obtaining the flap. The rats were distributed into 2 homogeneous groups: group 1 underwent both surgery and the use of HVES, whereas group 2 underwent just the surgery (control). Electrical stimulation was applied immediately after surgery and for 2 consecutive days. The percentage of necrotic area was analyzed using the Image J software, and blood flow was assessed by infrared thermography in different regions of the flap, divided into 4 zones according to the proximity of the pedicle of the inferior epigastric artery. The results were analyzed using a Student t test, where group 1 experienced a necrotic area of 26.2%, and group 2 had an area of 54.5%. Regarding the temperature, the 2 groups showed increase in the minimum and maximum temperature on the fourth postoperative day. The HVES appeared to have a positive influence on the viability of the flap.

  10. Tractographic reconstruction protocol optimization in the rat brain in-vivo: towards a normal atlas.

    Science.gov (United States)

    Preti, Maria Giulia; Di Marzio, Alessandro; Mastropietro, Alfonso; Aquino, Domenico; Baselli, Giuseppe; Laganà, Maria Marcella; Zucca, Ileana; Frassoni, Carolina; Spreafico, Roberto

    2011-01-01

    The tractographic reconstruction of anatomical and microstructural features provided by Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) gives essential information of brain damage in several pathological animal models. The optimization of a tractographic protocol is undertaken in normal rats for the future construction of a reference atlas, as prerequisite for preclinical pathological in-vivo studies. High field, preclinical in-vivo DTI faces important difficulties relevant to Signal-to-Noise Ratio (SNR), distortion, high required resolution, movement sensitivity. Given a pixel-size of 0.17 mm and TE/TR = 29/6500 ms, b value and slice thickness were fixed at 700 s/mm(2) and 0.58 mm, respectively, on preventive ex-vivo studies. In-vivo studies led to the choice of 30 diffusion directions, averaged on 16 runs. The final protocol required 51 min scanning and permitted a reliable reconstruction of main rat brain bundles. Tract reconstruction stopping rules required proper setting. In conclusion, the viability of DTI tractography on in-vivo rat studies was shown, towards the construction of a normal reference atlas.

  11. Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

    Directory of Open Access Journals (Sweden)

    Zhen Feng

    2015-01-01

    Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

  12. Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Yun Xiang; Huihua Liu; Tiebin Yan; Zhiqiang Zhuang; Dongmei Jin; Yuan Peng

    2014-01-01

    Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici-ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic ifbroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was signiifcantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.

  13. In vitro effect of direct current electrical stimulation on rat mesenchymal stem cells

    Science.gov (United States)

    Thottakkattumana Parameswaran, Vishnu; Barker, John Howard

    2017-01-01

    Background Electrical stimulation (ES) has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. Methods In the present study we exposed rat bone marrow- (BM-) and adipose tissue- (AT-) derived mesenchymal stem cells (MSCs) to direct current electrical stimulation (DC ES) and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. Results Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. Discussion This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.

  14. In vitro effect of direct current electrical stimulation on rat mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Sahba Mobini

    2017-01-01

    Full Text Available Background Electrical stimulation (ES has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. Methods In the present study we exposed rat bone marrow- (BM- and adipose tissue- (AT- derived mesenchymal stem cells (MSCs to direct current electrical stimulation (DC ES and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. Results Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. Discussion This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.

  15. In vitro effect of direct current electrical stimulation on rat mesenchymal stem cells.

    Science.gov (United States)

    Mobini, Sahba; Leppik, Liudmila; Thottakkattumana Parameswaran, Vishnu; Barker, John Howard

    2017-01-01

    Electrical stimulation (ES) has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. In the present study we exposed rat bone marrow- (BM-) and adipose tissue- (AT-) derived mesenchymal stem cells (MSCs) to direct current electrical stimulation (DC ES) and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.

  16. Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

    Science.gov (United States)

    McGillis, J P; Park, A; Rubin-Fletter, P; Turck, C; Dallman, M F; Payan, D G

    1989-07-01

    The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.

  17. INTERLEUKIN 10 INHIBITS THE RAT VSMC PROLIFERATION AND COLLAGEN SECRETION STIMULATED BY ANGIOTENSIN Ⅱ

    Institute of Scientific and Technical Information of China (English)

    夏春芳; 霍勇; 尹航; 朱国英; 唐朝枢

    2001-01-01

    Objective. To study the effect of interleukin 10 (IL-10) on the angiotensin II (AagII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism.Methods. On cultured VSMC of rat, 3H-thymine (3H-TdR) and 3H-proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively.Results. IL-10 (10-8 ~ 10-10g/ml) inhibited the increase of 3H-TdR and 3H-proline incorporation as well as FAK activity, which was induced by 10-7mol/L AngI ( P < 0. 05 or P < 0. 01 ). IL-10 also obviously downregulated the synthesis and secretion of collagen by AngII stimulated VSMC. But there was no difference in the protein expression of FAK among all the groups ( P > 0. 05).Conclusion. IL-10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngII.

  18. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    Directory of Open Access Journals (Sweden)

    David eDARDOU

    2015-01-01

    Full Text Available The loss of dopamine neurons observed in Parkinson’s disease (PD elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the dopamine 3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long term stimulation of the dopamine 3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

  19. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    Science.gov (United States)

    Dardou, David; Chassain, Carine; Durif, Franck

    2014-01-01

    The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

  20. Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

    Science.gov (United States)

    Olver, T Dylan; McDonald, Matthew W; Grisé, Kenneth N; Dey, Adwitia; Allen, Matti D; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Rice, Charles L; Melling, C W James; Noble, Earl G; Shoemaker, J Kevin

    2014-06-15

    Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

  1. Erythropoietin improves place learning in fimbria-fornix-transected rats and modifies the search pattern of normal rats

    DEFF Research Database (Denmark)

    Mogensen, Jesper; Miskowiak, Kamilla; Sørensen, Thomas Alrik

    2004-01-01

    The acquisition of a water-maze-based allocentric place learning task was studied in four groups of rats: two groups subjected to bilateral transections of the fimbria-fornix and two groups undergoing a sham control operation. At the moment of surgery all animals were given one systemic (intraper......The acquisition of a water-maze-based allocentric place learning task was studied in four groups of rats: two groups subjected to bilateral transections of the fimbria-fornix and two groups undergoing a sham control operation. At the moment of surgery all animals were given one systemic...... (intraperitoneal) injection of either human recombinant erythropoietin (EPO) (at a dosage of 5000 IU/kg body weight), given to one of the fimbria-fornix-transected groups and one of the sham-operated groups, or vehicle (saline), given to the two remaining groups. The 25-day task acquisition period (one session...... administration of EPO significantly improves the posttraumatic functional recovery of the presently studied place learning task after transections of the fimbria-fornix. Additionally, administration of EPO influences the strategy, although not quality, of task solution in normal (sham-operated) rats....

  2. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing

    2008-01-01

    and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver. RESULTS: Rat ED14 FLSPC were purified to 95% homogeneity and exhibited cell culture and gene expression characteristics expected for hepatic stem/progenitor cells...

  3. Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sara Botschuijver

    2016-01-01

    Full Text Available Background: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS. In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men.  Methodology and findings: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR by electromyography (EMG to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension. Conclusions: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS.

  4. Effect of low frequency repetitive transcranial magnetic stimulation on kindling-induced changes in electrophysiological properties of rat CA1 pyramidal neurons.

    Science.gov (United States)

    Moradi Chameh, Homeira; Janahmadi, Mahyar; Semnanian, Saeed; Shojaei, Amir; Mirnajafi-Zadeh, Javad

    2015-05-01

    In this study, the effect of repetitive transcranial magnetic stimulation (rTMS) on the kindling induced changes in electrophysiological firing properties of hippocampal CA1 pyramidal neurons was investigated. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (240 pulses at 1 Hz) at 5 min after termination of daily kindling stimulations. Twenty-four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using a whole-cell patch clamp technique, under current clamp condition. Amygdala kindling significantly decreased the adaptation index, post-afterhyperpolarization, rheobase current, utilization time, and delay to the first rebound spike. It also caused an increase in the voltage sag, number of rebound spikes and number of evoked action potential. Results of the present study revealed that application of rTMS following kindling stimulations had antiepileptogenic effects. In addition, application of rTMS prevented hyperexcitability of CA1 pyramidal neurons induced by kindling and conserved the normal neuronal firing.

  5. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

    1997-03-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  6. Gastric lipase in alcoholic pancreatitis. Comparison of secretive profiles following pentagastrin stimulation in normal adults and patients with pancreatic insufficiency.

    Science.gov (United States)

    Moreau, J; Bouisson, M; Balas, D; Ravaud, A; Stupnik, S; Buscail, L; Vaysse, N; Ribet, A

    1990-07-01

    The aims of this study were to evaluate the amount of gastric lipase secreted by the stomach in normal adults and to elucidate a possible adaptative secretion of this enzyme in response to pancreatic insufficiency secondary to alcoholic chronic pancreatitis. Forty-one subjects underwent a gastric intubation. Pentagastrin (6 micrograms.kg-1.h-1 IV) significantly increased gastric lipase concentration and output. Stimulated gastric lipase output in seven normal subjects was 12,598 +/- 2036 U/h (by using tributyrin as substrate). Outputs where higher (P less than 0.02) in 17 patients with pancreatic insufficiency who were not drinking alcohol, but were not significantly different in nine patients who continued to drink (20,413 +/- 1778 U/h and 21,953 +/- 4973 U/h, respectively). On the other hand, high gastric lipase outputs were found in eight patients with duodenal ulcers and no evidence of pancreatic dysfunction (23,180 +/- 262 U/h). The time required to reach maximal lipase output (peak output) following pentagastrin stimulation was the same in all groups (approximately 38 minutes) except for the group of patients with pancreatic insufficiency who did not drink alcohol, in whom it was significantly reduced (approximately 26.5 minutes). Secretory patterns of gastric lipase and pepsin were closely comparable. Gastric lipase secretion could be increased in several clinical conditions and particularly in patients with pancreatic insufficiency caused by alcoholic chronic pancreatitis who have been abstinent for a long time.

  7. Selective protection of normal hepatocytes by indocyanine green in photodynamic therapy for the hepatoma of rat

    Science.gov (United States)

    Gu, Ying; Li, Junheng; Guo, Zhong-He

    1993-03-01

    Using hepatocarcinoma transplanted rats, the present study made consecutive observation for the color change and indocyanine green (ICG) absorption peak of the normal liver and tumor tissues after intravenous injection of ICG. The normal liver tissue of the rat was found to turn violet-green soon after ICG injection and the optic density (OD) of ICG-characteristic spectral peak of the tissue homogenate reached its maximum value at 35 minutes post-injection, while neither color change nor OD value increase was noticed in the tissue of transplanted hepatocarcinoma, suggesting that there is a specific absorption of ICG by the normal liver tissue. Chemiluminescentoassay revealed inhibited luminal chemiluminescence by ICG, indicating the depression of singlet oxygen and reactive oxygen species (ROS) oxidation during HPD photosensitization by ICG. In PDT of the hepatocarcinoma, the irradiated area was examined under microscope and auto-microimage analysis system after ICG administration. For tumor-free tissue, the photosensitization induced necrotic area was found smaller in those with than those without ICG administration, whereas the tumor killing effect was almost the same of the two. It is suggested that ICG may offer selective protection for healthy hepatocytes without diminishing the destruction of tumor cells. The protection of healthy hepatocytes by ICG is thought to be in accordance with the amount of ICG in the cell and the distribution of light energy.

  8. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    Chun LIANG; Zong-gui WU; Jian DING; Jian-fei JIANG; Gao-zhong HUANG; Rong-zeng DU; Jun-bo GE

    2004-01-01

    AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto induce experimental atheroma. Then either placebo or losartan 50 mg.kg-1.d-1 was administered in rats for another2 months. In vitro, the effect of losartan 0.1-10 μmol/L on the expression of MMP-2 and MMP-9 was investigated in Ang Ⅱ-stimulated rat peritoneal macrophages. The expression and activity of MMP-2 and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2 and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2 and MMP-9 compared with the placebo group (MMP-2, 5861±539 vs 8991±965, P<0.05; MMP-9,10527±1002 vs 14623±2462, P<0.01). In cultured rat peritoneal macrophages, Ang Ⅱ 0.1 μmol/L elicited an increase in MMP-2 and MMP-9 activity and expression that were prevented by losartan in a dose-dependent manner(P<0.01). But the AT2receptor antagonist PD123319 had no effect. CONCLUSION: Losartan reduced the expression and activity of MMP-2 and MMP-9 in rat atherosclerotic lesions. The anti-atherogenic effects of losartan were due to the direct inhibition of Ang Ⅱ bioactivity.

  9. Suppression of motor cortical excitability in anesthetized rats by low frequency repetitive transcranial magnetic stimulation.

    Directory of Open Access Journals (Sweden)

    Paul A Muller

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is a widely-used method for modulating cortical excitability in humans, by mechanisms thought to involve use-dependent synaptic plasticity. For example, when low frequency rTMS (LF rTMS is applied over the motor cortex, in humans, it predictably leads to a suppression of the motor evoked potential (MEP, presumably reflecting long-term depression (LTD -like mechanisms. Yet how closely such rTMS effects actually match LTD is unknown. We therefore sought to (1 reproduce cortico-spinal depression by LF rTMS in rats, (2 establish a reliable animal model for rTMS effects that may enable mechanistic studies, and (3 test whether LTD-like properties are evident in the rat LF rTMS setup. Lateralized MEPs were obtained from anesthetized Long-Evans rats. To test frequency-dependence of LF rTMS, rats underwent rTMS at one of three frequencies, 0.25, 0.5, or 1 Hz. We next tested the dependence of rTMS effects on N-methyl-D-aspartate glutamate receptor (NMDAR, by application of two NMDAR antagonists. We find that 1 Hz rTMS preferentially depresses unilateral MEP in rats, and that this LTD-like effect is blocked by NMDAR antagonists. These are the first electrophysiological data showing depression of cortical excitability following LF rTMS in rats, and the first to demonstrate dependence of this form of cortical plasticity on the NMDAR. We also note that our report is the first to show that the capacity for LTD-type cortical suppression by rTMS is present under barbiturate anesthesia, suggesting that future neuromodulatory rTMS applications under anesthesia may be considered.

  10. The effect of adrenal demedullation on cardiovascular responses to environmental stimulation in conscious rats.

    Science.gov (United States)

    Borkowski, K. R.; Kelly, E.

    1986-01-01

    Circulating plasma adrenaline has been implicated in the facilitation of neurogenic pressor responses and development of hypertension. Bilateral adrenal demedullation in rats did not affect body weight, urine output, urinary electrolyte (Na+, K+ and Cl-) excretion, nor plasma corticosterone concentration, indicating the selective nature of the demedullation procedure. Adrenal demedullation did induce significant reductions in adrenal catecholamine content, plasma adrenaline levels, resting blood pressure and heart rate in conscious rats, but did not affect alerting-induced increases in blood pressure. The adrenal medulla and circulating plasma adrenaline appear to contribute to the maintenance of resting cardiovascular parameters, but would not appear to be involved in nor facilitate the cardiovascular responses to environmental stimulation. PMID:3742165

  11. Effects of repetitive transcranial magnetic stimulation on synaptic plasticity and apoptosis in vascular dementia rats.

    Science.gov (United States)

    Yang, Hui-Yun; Liu, Yang; Xie, Jia-Cun; Liu, Nan-Nan; Tian, Xin

    2015-03-15

    This study aims to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) protects pyramidal cells from apoptosis and promotes hippocampal synaptic plasticity in a vascular dementia (VaD) rat model. Following establishment of a VaD rat model using two-vessel occlusion (2VO), learning and memory were evaluated via the Morris Water Maze (MWM), hippocampal CA1 neuron ultrastructure was examined via electron microscopy, and hippocampal synaptic plasticity was assessed by long-term potentiation (LTP). Western blot was used to detect the expression of N-methyl-d-aspartic acid receptor 1 (NMDAR1), Bcl-2, and Bax. Compared with VaD group, rats treated with low-frequency rTMS had reduced-escape latencies, increased swimming time in the target quadrant (PCA3-CA1 synapses was enhanced (P<0.05). Low-frequency rTMS significantly up-regulated NMDAR1 and Bcl-2 expression and down-regulated Bax expression. Low-frequency rTMS improves learning and memory, protects the synapse, and increases synaptic plasticity in VaD model rats. Increased Bcl-2 expression and reduced Bax expression may be a novel protective mechanism of low-frequency rTMS treatment for VaD.

  12. Activation of peroxisome proliferator-activated receptor alpha in rat spinal cord after peripheral noxious stimulation.

    Science.gov (United States)

    Benani, A; Heurtaux, T; Netter, P; Minn, A

    2004-10-07

    Following recurrent noxious stimulation, both functional modification and structural reorganization such as activation of the arachidonate cascade or axon sprouting occur in the central nervous system (CNS). It has been recently proposed that these alterations observed during chronic pain state were supported by an intensification of the lipid metabolism. In this regard, it has been shown that mRNA coding for several fatty acid metabolizing enzymes are up-regulated in the rat lumbar spinal cord in response to persistent nociception induced by a peripheral inflammation. As peroxisome proliferators-activated receptor (PPAR) could mediate such effects, we therefore investigated the activation of this transcription factor in the rat spinal cord following subcutaneous injection of complete Freund's adjuvant (CFA) into a hind paw. In this study, we compared the DNA-binding activity of nuclear proteins extracted from healthy and inflamed rats toward a PPAR response element. Using electrophoretic mobility-shift assay (EMSA), we found that only the PPARalpha isoform was activated in the rat spinal cord after CFA injection. This activation occurred rapidly, as early as 30 min post-CFA injection, and was persistent up to 10 h, reaching a maximum at 6h after CFA injection. In view of the consequences of PPARalpha activation in other tissues, these results suggest that fatty acid utilization is enhanced in the CNS during chronic pain state. Although the physiopathological relevance of PPARalpha activation during hyperalgesia needs further investigation, we provided here a new player in the molecular modeling of pain pathways.

  13. Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

    DEFF Research Database (Denmark)

    Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell...

  14. Blood flow activation in rat somatosensory cortex under sciatic nerve stimulation revealed by laser speckle imaging

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In many functional neuroimaging research the change of local cerebral blood flow (CBF) induced by sensory stimulation is regarded as an indicator of the change in cortical neuronal activity although a precise and full spatio-temporal description of local CBF response coupled to neural activity has still not been laid out. Using the laser speckle imaging technique a relatively large exposed area in somatosensory cortex of rat was imaged for the observation of the variations of CBF during sciatic nerve stimulation. The results showed that cerebral blood flow activation was spatially localized and discretely distributed in the targeted microvasculature. Individual arteries, veins and capillaries in different diameters were activated with the time going. The response pattern of CBF related to the function of brain activity and energy metabolism is delineated exactly.

  15. Enhanced extinction of aversive memories by high-frequency stimulation of the rat infralimbic cortex.

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    Full Text Available Electrical stimulation of the rodent medial prefrontal cortex (mPFC, including the infralimbic cortex (IL, immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA. IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion.

  16. Exogenous normal lymph alleviates microcirculation disturbances and abnormal hemorheological properties in rats with disseminated intravascular coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Yu-Ping [Institute of Microcirculation, Hebei North University, Zhangjiakou (China); Hou, Ya-Li [Department of Clinical Laboratory, First Affiliated Hospital, Hebei North University, Zhangjiakou (China); Li, Jun-Jie; Jiang, Hua; Zhang, Jing [Institute of Microcirculation, Hebei North University, Zhangjiakou (China)

    2013-02-01

    Disturbances of the microcirculation and abnormal hemorheological properties are important factors that play an important role in disseminated intravascular coagulation (DIC) and result in organ dysfunction or failure. In the present study, we established an animal model of DIC using intravenous Dextran 500 in rats, and used exogenous normal lymph corresponding to 1/15 of whole blood volume for injection through the left jugular vein. We found that normal lymph could improve the blood pressure and survival time of rats with DIC. The results regarding the mesenteric microcirculation showed that the abnormality of the diameter of mesenteric microvessels and micro-blood flow speed in the DIC+lymph group was significantly less than in the DIC+saline group. Whole blood viscosity, relative viscosity, plasma viscosity, hematocrit (Hct), erythrocyte sedimentation rate (ESR), and electrophoresis time of erythrocytes were significantly increased in the DIC+saline group compared to the control group. The electrophoretic length and migration of erythrocytes from the DIC+saline and DIC+lymph groups were significantly slower than the control group. Blood relative viscosity, Hct, ESR, and electrophoretic time of erythrocytes were significantly increased in the DIC+lymph group compared to the control group. Whole blood viscosity, relative viscosity and reduced viscosity were significantly lower in the DIC+lymph group than in the DIC+saline group, and erythrocyte deformability index was also significantly higher than in the DIC+saline and control groups. These results suggest that exogenous normal lymph could markedly improve the acute microcirculation disturbance and the abnormal hemorheological properties in rats with DIC induced by Dextran 500.

  17. Fentanyl inhibits glucose-stimulated insulin release from β-cells in rat pancreatic islets

    Institute of Scientific and Technical Information of China (English)

    Tao-Lai Qian; Xin-Hua Wang; Sheng Liu; Liang Ma; Ying Lu

    2009-01-01

    AIM:To explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture.METHODS: Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation.The islets were divided into four groups according to the fentanyl concentration: control group (0 ng/mL),group Ⅰ (0.3 ng/mL), group Ⅱ (3.0 ng/mL), and group Ⅲ (30 ng/mL). In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl + 0.1 μg/mL naloxone or fentanyl + 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations (2.8 mmol/L and 16.7 mmol/L,respectively) of glucose was investigated and electron microscopy morphological assessment was performed.RESULTS: Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups Ⅱ and Ⅲ (62.33 ±9.67 μIU vs 47.75 ±96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P <0.01) and was lowest in group Ⅲ ( P < 0.01). After adding 1 μg/mL naloxone, insulin release in groups Ⅱ and Ⅲ was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/mL fentanyl.CONCLUSION: Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.howed that the isl

  18. Effects of electrical stimulated hypothalamuic paraventricular nucleus ongastric ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian Fu Zhang; Yong Mei Zhang; Chang Dong Yan

    2000-01-01

    AIM To investigate the effect and regulation of electrical stimulation on the paraventricular nucleus (PVN)of hypothalamus using rat gastric ischemia-reperfusion injury (I-RI)induced ulcer model.METHODS Adult male Sprague-Dawley rats weighing 150 g-250 g were used. The surgically prepared ratswere kept fasting for 24 h, but allowed free access to water. They were then anesthetized with urathane(1 g/kg), the celiac artery was clamped with a small clip (holding force 145 g) for 30min, reperfusion wasestablished by removal of the clamp, 60min after reperfusion, the rats were killed and their stomachs wereremoved and perfused intragastrically with 100 mL/L formalin for 30min, and the ulcer index was scoredaccording to Guth et al. The PVN was obtained according to atlas of Paxinos and Watson. The electrodesand cannula were inserted into the PVN for the electrical stimulation, electrical injury and PVN injection,RESULTS In control group (30min ischemia and 60ain reperfusion only), ulcer index was 184.70±60.80(n = 8); in electrical stimulations of PVN (0.2mA, 0.4mA and 0.6mA) + I-RI group, ulcer indexes were102.40±20.39, 85.37±39.76 and 45.00±19.04 (n =8) respectively. Compared with the control groupthere was significant difference ( P < 0.01) in a dose-dependent manner. In electrical lesion of bilateral PVN+ I-RI group, ulcer index was greatly increased (230.00±47.30, n = 8). Microinjection of 3% L-glutamate0.5μL into PVN could produce similar effect to that of PVN stimulation (ulcer index 75.14±37.18, n = 8).A further study indicated that the MDA, pepsin activity and gastric acidity were reduced by PVN stimulationbut no obvious changes of gastric juice volume, total acid output and gastric mucus barrier were observed.CONCLUSION The PVN is one of the specific CNS areas capable of protecting the gastric ischemic-reperfusion injury in rats, and related to decreased MPA, pepsin activity, gastric acidity, while gastric juicevolume, total acid output and gastric

  19. INTRAPANCREATIC CHOLECYSTOKININ MEDIATES VAGALLY STIMULATED EXOCRINE SECRETION FROM THE RAT PANCREAS

    Institute of Scientific and Technical Information of China (English)

    何晓东; MTimothyNelson; HaileTDebas

    1996-01-01

    Although cholecystokinin is localized within neuronal fibres of the pancreas, a physiological role for intrapancreatic cholecystokinin has not been identified. The strategy of this study was to elicit pure vagal stlmulatbx electrically, and to use specific receptor antagonists to idetxtify the mediators of exocrine pancreatic secretion. We conclude that vagal stimulation of the rat pancreas involves ganglionicand neurotransmission and release of acetylcholine and cholecystokinin from intrapanereatic, postganglionic fibres. To our knowledge, this is the first study to demonstrate a physiological role for intrapancreatic cholecystokinin.

  20. Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

    DEFF Research Database (Denmark)

    Novak, Ivana; Hede, Susanne; Hansen, Mette

    2007-01-01

    these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell......, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini...

  1. Investigating the Anticonvulsant Effects of Repetitive Transcranial Magnetic Stimulation on Perforant Path Kindling Model in Rats

    Directory of Open Access Journals (Sweden)

    Ali Yadollahpour

    2015-02-01

    Full Text Available Background: Almost 20% of epileptics are drug resistant. Studies have shown that low frequency repetitive transcranial magnetic stimulation (rTMS is with therapeutic effects on epilepsy-affected laboratory models. Anticonvulsant effects of rTMS depend on several parameters among which radiation frequency is the most important one. In this study, the therapeutic impacts of 1 and 2 Hz rTMS on convulsing parameters in epileptic model of electrical kindling stimulation of the perforant path were investigated. Materials and Methods: In this experimental study 21 rats were randomly divided into three groups, namely ‘1 Hz treatment group’ and ‘2 Hz treatment group’ and ‘kindling group’. The kindling group only received kindling stimulations for seven days. One Hz and 2 Hz frequency treatment groups received maximally 5 min rTMS after termination of kindling stimulation per day for a week. Stimulation and stability electrodes had been placed, in turn, on perforant path and dentate gyrus. For quantifying the duration of the subsequent discharge waves, two-way ANOVA test and Bonferroni post-test were employed. In addition, for quantifying the convulsive behaviors, Kruskal-Wallis and the Mann-Whitney U tests were used. Results: The results showed that 1 Hz and 2 Hz frequency rTMS have considerable inhibitory impact on the development of convulsive phases. Anticonvulsive effect was observed from the first day after rTMS was undertaken. In addition, the animals did not show fourth and fifth convulsive stages, and a significant reduction was evident in their recorded peak discharge waves compared with kindle group. Conclusion: Low frequency rTMS possesses significant anticonvulsive effects which depend upon sTMS stimulation frequency.

  2. Aloe vera gel facilitates re-epithelialization of corneal alkali burn in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Atiba A

    2015-10-01

    Full Text Available Ayman Atiba,1 Tamer Wasfy,2 Walied Abdo,3 Ahmed Ghoneim,2 Tarek Kamal,4 Mustafa Shukry5 1Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 2Department of Ophthalmology, Faculty of Medicine, Tanta University, 3Department of Pathology, 4Department of Biochemistry, 5Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt Purpose: To investigate the efficacy of topical applied aloe vera (AV and to facilitate the repair of the standardized alkaline corneal ulcer in normal and diabetic rats.Materials and methods: The corneal alkali-burn injury model was established unilaterally in Wistar rats by filter paper saturated with 0.01 M NaOH contacting the eyes for 45 seconds. Rats were divided into four groups: normal control (NC, normal AV (NAV, diabetic control (DC, and diabetic AV (DAV. NAV and DAV groups were treated with AV gel eye drops four times daily, and NC and DC groups were treated with normal saline for 3 days. Corneal epithelial wound closure and degree of edema were recorded using slit lamp and optical coherence tomography at 0, 24, 48, and 72 hours postwounding. Histological examination was conducted to evaluate the degree of inflammation and the healing effect.Results: Corneal epithelial wound healing was better in the NAV group than in the NC group, and it was significantly higher in the DAV group than in the DC group (P<0.05. In comparison to the DC group, DAV treated with AV demonstrated a marked reduction in edema at 48 and 72 hours. Histologically, corneal re-epithelialization was complete and higher in DAV group than that in DC group; moreover, the inflammatory cells were increased in DC group than DAV group (P<0.05.Conclusion: This study demonstrated the efficacy of AV for enhanced corneal re-epithelialization, as well as reduced inflammatory response after alkali burn in rats; therefore, it could be useful as a

  3. Electrophysiological effect of HeNe laser on normal and injured sciatic nerve in the rat.

    Science.gov (United States)

    Rochkind, S; Nissan, M; Razon, N; Schwartz, M; Bartal, A

    1986-01-01

    The effect of low energy CW HeNe laser irradiation on normal and dissected nerves in the rat was examined. The methods are described. Results are compared to the laser effect on other living tissues. HeNe irradiation was found to increase significantly the action potentials of the nerves. It was found to be a long-lasting effect, keeping an increase in the nerves action potential for more than eight months after irradiation has been stopped. A possible explanation for the way the irradiation acts on the nerve is suggested.

  4. Dissociation and trafficking of rat GABAB receptor heterodimer upon chronic capsaicin stimulation.

    Science.gov (United States)

    Laffray, Sophie; Tan, Kelly; Dulluc, Josette; Bouali-Benazzouz, Rabia; Calver, Andrew R; Nagy, Frédéric; Landry, Marc

    2007-03-01

    Gamma-aminobutyric acid type B receptors (GABAB) are G-protein-coupled receptors that mediate GABAergic inhibition in the brain. Their functional expression is dependent upon the formation of heterodimers between GABAB1 and GABAB2 subunits, a process that occurs within the endoplasmic reticulum. However, the mechanisms that regulate GABAB receptor oligomerization at the plasma membrane remain largely unknown. We first characterized the functional cytoarchitecture of an organotypic co-culture model of rat dorsal root ganglia and spinal cord. Subsequently, we studied the interactions between GABAB subunits after chronic stimulation of sensory fibres with capsaicin. Surface labelling of recombinant proteins showed a decrease in subunit co-localization and GABAB2 labelling, after capsaicin treatment. In these conditions, fluorescence lifetime imaging measurements further demonstrated a loss of interactions between green fluorescent protein-GABAB1b and t-dimer discosoma sp red fluorescent protein-GABAB2 subunits. Finally, we established that the GABAB receptor undergoes clathrin-dependent internalization and rapid recycling to the plasma membrane following activation with baclofen, a GABAB agonist. However, in cultures chronically stimulated with capsaicin, the agonist-induced endocytosis was decreased, reflecting changes in the dimeric state of the receptor. Taken together, our results indicate that the chronic stimulation of sensory fibres can dissociate the GABAB heterodimer and alters its responsiveness to the endogenous ligand. Chronic stimulation thus modulates receptor oligomerization, providing additional levels of control of signalling.

  5. Digestive stimulant action of three Indian spice mixes in experimental rats.

    Science.gov (United States)

    Platel, Kalpana; Rao, Alkananda; Saraswathi, G; Srinivasan, K

    2002-12-01

    The present study examined the favourable influence of three spice mixes derived from a few commonly consumed spices of known digestive stimulant action on digestive enzymes of pancreas and small intestine, and on bile secretion and composition in experimental rats. The common ingredients of these mixes were coriander, turmeric, red chilli, black pepper and cumin, while the spice mix II additionally had ginger, and spice mix III contained onion. All the three spice mixes favourably enhanced the activities of pancreatic lipase, chymotrypsin and amylase when consumed during the diet. In addition, these spice mixes brought about a pronounced stimulation of bile flow and of bile acid secretion. Among the three spice mixes examined, spice mix III which is customized so as to include spices that are desirable from the point of view of stimulation of digestion, had the highest stimulatory influence particularly on bile secretion, bile acid output and the activities of pancreatic enzymes. While activities of pancreatic lipase, amylase and chymotrypsin were elevated by 40, 16 and 77%, respectively, the bile volume as well as the bile acid secretion were almost doubled in spice mix III treatment. The higher secretion of bile especially with an elevated level of bile acids and a beneficial stimulation of pancreatic digestive enzymes, particularly of lipase could probably be the two mechanisms by which these combinations of spices aid in digestion.

  6. Somatosensory stimulation suppresses the excitability of pyramidal cells in the hippocampal CA1 region in rats

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zhouyan Feng; Jing Wang; Xiaojing Zheng

    2014-01-01

    The hippocampal region of the brain is important for encoding environment inputs and memory formation. However, the underlying mechanisms are unclear. To investigate the behavior of indi-vidual neurons in response to somatosensory inputs in the hippocampal CA1 region, we recorded and analyzed changes in local ifeld potentials and the ifring rates of individual pyramidal cells and interneurons during tail clamping in urethane-anesthetized rats. We also explored the mechanisms underlying the neuronal responses. Somatosensory stimulation, in the form of tail clamping, chan-ged local ifeld potentials into theta rhythm-dominated waveforms, decreased the spike ifring of py-ramidal cells, and increased interneuron ifring. In addition, somatosensory stimulation attenuated orthodromic-evoked population spikes. These results suggest that somatosensory stimulation sup-presses the excitability of pyramidal cells in the hippocampal CA1 region. Increased inhibition by local interneurons might underlie this effect. These ifndings provide insight into the mechanisms of signal processing in the hippocampus and suggest that sensory stimulation might have thera-peutic potential for brain disorders associated with neuronal hyperexcitability.

  7. Stimulation of acid secretion and phosphoinositol production by rat parietal cell muscarinic M sub 2 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pfeiffer, A.; Rochlitz, H.; Herz, A.; Paumgartner, G. (Univ. of Munich (West Germany))

    1988-04-01

    The muscarinic receptor system involved in hydrogen production by enriched rat gastric parietal cells was investigated. Muscarinic receptor density determined by (N-methyl-{sup 3}H)scopolamine binding was 8,100/cell. The receptor appeared to be of the M{sub 2} muscarinic receptor subtype, since it had a low affinity (K{sub d} 189 nM) for the M{sub 1} receptor antagonist pirenzepine compared with atropine. Receptor activation by carbachol rapidly augmented levels of polyphosphoinositides, indicating an activation of phospholipase C. The dose-response relations for the increase in inositol phosphates closely paralleled the binding of carbachol to muscarinic receptors. The inositol phosphate response was antagonized by pirenzepine with a K{sub i} of 177 nM. the stimulation of inositol phosphate levels by carbachol correlated well with the stimulation of ({sup 14}C)aminopyrine uptake, determine as an index of acid secretion. The muscarinic agonists oxotremorine, pilocarpine, and bethanechol elicited partial increases in inositol phosphates at maximal drug concentrations, and these partial increases correlated with their ability to stimulate ({sup 14}C)aminopyrine uptake. These data indicate that inositolpolyphosphates may be a second messenger of M{sub 2} receptors stimulating acid secretion.

  8. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Durand, M.T.; Mota, A.L. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Barale, A.R. [Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG (Brazil); Castania, J.A.; Fazan, R. Jr.; Salgado, H.C. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-16

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

  9. Simulation of injury potential compensation by direct current stimulation in rat spinal cord.

    Science.gov (United States)

    Wang, Aihua; Zhang, Guanghao; Zhang, Cheng; Wu, Changzhe; Song, Tao; Huo, Xiaolin

    2014-01-01

    Injury potential, a significant index of spinal cord injury (SCI), is generated by the movement of extracellular ions. It can be compensated through applied direct current (DC) stimulation, which prevents the influx of the free calcium, and eventually reduces the development of secondary injury. Therefore, the compensation of injury potential is beneficial to the repairing of the function of spinal cord. The compensation effect can be evaluated by whether the magnitudes of longitudinal electric fields (EFs) are compensated to zero. However, there have been no established criteria to determine the distribution and shape of stimulating electrodes. In this study, in order to optimize the stimulating electrodes, a finite element model (FEM) of rat spinal cord was developed, and the EFs changes induced by electrodes of different sizes, shapes and locations after SCI were calculated. All the designed configurations of electrodes were able to compensate injury potential, but the resultant compensation effects vary. Pin and disc electrodes produced uneven EFs, while ring electrodes produced uniformly distributed EFs. Moreover, large ring electrodes can compensate the longitudinal EFs almost to zero with relatively low current density (0.55 μA/mm(2)) applied. These results provide a basis for the determination of electrical stimulation parameters in the compensation of injury potential.

  10. PLASMA EXTRAVASATION IN THE VISCERAL ORGANS CAUSED BY ELECTRICAL STIMULATION OF ACUPOINT "ZUSANLI" IN RATS

    Institute of Scientific and Technical Information of China (English)

    曹东元; 牛汉璋; 赵晏; 张世红; 王莹

    2002-01-01

    Objective To investigate the plasma extravasation of visceral organs caused by electrical stimulation of acupoint under the dorsal root reflex and ax on reflex conditions. Methods By the means of measuring th e content of Evans blue, this study investigated the plasma extravasation of vis ceral organs induced by electrical stimulation of acupoint "Zusanli"(ST 36). Results The Evans blue content in the visceral organs such as liver , spleen, pancreas and the whole gastrointestinal tract in rats increased signif icantly after electrical stimulation of acupoint "Zusanli" compared with that of the control group (P<0.01). The Evans blue extravasation in the above visce ral organs was blocked by pre-treatment of capsaicin (66 mmol*L-1, 50 μ L) into the acupoint. Conclusion The neurogenic inflammation o f the visceral organs evoked by electrical stimulation of acupoint was mediated by the capsaicin-sensitive afferent fibers through the dorsal root reflex and a xon reflex. It is a new method to study the correlation of meridian-viscera.

  11. Inhibition of gastric motility by noxious chemical stimulation of interspinous tissues in the rat.

    Science.gov (United States)

    Budgell, B; Suzuki, A

    2000-05-12

    In urethane anesthetized, adult male Wistar rats, noxious chemical stimulation of the mid to lower thoracic interspinous tissues, in the form of capsaicin injection, was accompanied by a pronounced increase in gastric sympathetic nerve activity and inhibition of gastric motility. Much weaker effects on gastric sympathetic nerve activity and gastric motility were observed with similar stimulation of the lower lumbar interspinous tissues. The inhibitory response of gastric motility to thoracic stimulation was preserved in spinalized animals, somewhat diminished in vagotomized animals and was abolished in most animals from which the coeliac ganglion had been extirpated. In vagotomized animals, treatment with 1 mg/kg propranolol i.v. did not cause any further attenuation of the inhibitory reflex. However, the inhibitory reflex was extinguished in vagotomized animals which received 1 mg/kg propranolol plus 10 mg/kg phentolamine i.v. These results suggest that noxious chemical stimulation of the interspinous tissues elicits a segmentally organized reflex which is mediated principally at the spinal level and which expresses itself principally, but not exclusively via sympathetic efferents traversing the coeliac ganglion. The expression of the reflex response appears to be largely dependent upon the integrity of alpha adrenergic receptors.

  12. Amygdala kindling potentiates seizure-stimulated immediate-early gene expression in rat cerebral cortex.

    Science.gov (United States)

    Duman, R S; Craig, J S; Winston, S M; Deutch, A Y; Hernandez, T D

    1992-11-01

    Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute electroconvulsive seizure (ECS). Although amygdala kindling did not significantly influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in the cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was dependent on the time course of kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased in stage 2 kindled animals. ECS-stimulated levels of c-jun and NGF1-A mRNA were also significantly increased in cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was long-lasting because an acute ECS stimulus significantly elevated levels of c-fos and c-jun mRNA in the cerebral cortex of animals that were kindled 5 months previously. In contrast to these effects in cerebral cortex, kindling did not influence ECS-stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical studies revealed lamina-specific changes in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats

    Directory of Open Access Journals (Sweden)

    Zhou Jian-Lin

    2011-09-01

    Full Text Available Abstract Background Pulsed electromagnetic fields (PEMF stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms. Methods Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1 PEMF stimulation group (PEMF group, n = 24: intravenously injected with lipopolysaccharide (LPS, 10 μg/kg on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2 Methylprednisolone-treated group (MPSL group, n = 24: injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3 Control group (PS group, n = 24: injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor β1 (TGF-β1 in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline injection. Results The incidence of osteonecrosis in the PEMF group (29% was significantly lower than that observed in the MPSL group (75%, while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-β1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-β1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks. Conclusions PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms

  14. Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

    Directory of Open Access Journals (Sweden)

    Shuxing Wang

    Full Text Available Melatonin plays a protective role in type 2 diabetes (T2D through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30 min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa and Zucker lean (ZL, +/fa littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naïve ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbAlc levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbAlc levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world.

  15. Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

    Science.gov (United States)

    Wang, Shuxing; Zhai, Xu; Li, Shaoyuan; McCabe, Michael F; Wang, Xing; Rong, Peijing

    2015-01-01

    Melatonin plays a protective role in type 2 diabetes (T2D) through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS) is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30 min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa) and Zucker lean (ZL, +/fa) littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naïve ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbAlc) levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbAlc levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world.

  16. Distinct behavioral phenotypes in novel "fast" kindling-susceptible and "slow" kindling-resistant rat strains selected by stimulation of the hippocampal perforant path.

    Science.gov (United States)

    Langberg, Tomer; Dashek, Ryan; Mulvey, Bernard; Miller, Kimberly A; Osting, Susan; Stafstrom, Carl E; Sutula, Thomas P

    2016-01-01

    Kindling is a phenomenon of activity-dependent neural circuit plasticity induced by repeated seizures that results in progressive permanent increases in susceptibility to epilepsy. As the permanent structural and functional modifications induced by kindling include a diverse range of molecular, cellular, and functional alterations in neural circuits, it is of interest to determine if genetic background associated with seizure-induced plasticity might also influence plasticity in neural circuitry underlying other behaviors. Outbred Sprague-Dawley (SD) rats were selected and bred for ~15 generations for "fast' or "slow" rates of kindling development in response to stimulation of the perforant path input to the hippocampus. After 7-8 generations of selection and breeding, consistent phenotypes of "fast" and "slow" kindling rates were observed. By the 15th generation "fast" kindling rats referred to as Perforant Path Kindling Susceptible (PPKS) rats demonstrated a kindling rate of 10.7 ± 1.1 afterdischarges (ADs) to the milestone of the first secondary generalized (Class V) seizure, which differed significantly from "slow" kindling Perforant Path Kindling Resistant (PPKR) rats requiring 25.5 ± 2.0 ADs, and outbred SD rats requiring 16.8 ± 2.5 ADs (pkindling) strain with increased susceptibility to seizure-induced plasticity demonstrated statistically significant increases in motor exploratory activity in the open field test and reduced spatial learning the Morris water maze, but demonstrated normal fear conditioned learning comparable to outbred SD rats and the "slow" kindling-resistant PPKR strain. These results confirm that selection and breeding on the basis of responses to repeated pathway activation by stimulation can produce enduring modification of genetic background influencing behavior. These observations also suggest that genetic background underlying susceptibility or resistance to seizure-induced plasticity in hippocampal circuitry also differentially

  17. Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

    Science.gov (United States)

    Kandel, Sunil Mani

    Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia

  18. Nitric oxide synthase inhibition delays low-frequency stimulation-induced satellite cell activation in rat fast-twitch muscle.

    Science.gov (United States)

    Martins, Karen J B; MacLean, Ian; Murdoch, Gordon K; Dixon, Walter T; Putman, Charles T

    2011-12-01

    This study examined the effect of nitric oxide synthase (NOS) inhibition via N(ω)-nitro-l-arginine methyl ester (l-NAME) administration on low-frequency stimulation-induced satellite cell (SC) activation in rat skeletal muscle. l-NAME only delayed stimulation-induced increases in SC activity. Also, stimulation-induced increases in hepatocyte growth factor (HGF) mRNA and protein expression were only abrogated at the mRNA level in l-NAME-treated animals. Therefore, early stimulation-induced SC activation appears to be NOS-dependent, while continued activation may involve NOS-independent HGF translational control mechanisms.

  19. Microscopic hyperspectral imaging studies of normal and diabetic retina of rats

    Institute of Scientific and Technical Information of China (English)

    LI QingLi; XUE YongQi; ZHANG JingFa; XIAO GongHai

    2008-01-01

    A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina seotions of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color Images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

  20. Microscopic hyperspectral imaging studies of normal and diabetic retina of rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina sections of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

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

    Science.gov (United States)

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

    1986-01-01

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

  2. Levan from Bacillus subtilis Natto: its effects in normal and in streptozotocin-diabetic rats.

    Science.gov (United States)

    de Melo, Fernando Cesar Bazani Cabral; Zaia, Cássia Thaïs Bussamra Viera; Celligoi, Maria Antonia Pedrine Colabone

    2012-10-01

    Levan is an exopolysaccharide of fructose primarily linked by β-(2→6) glycosidic bonds with some β-(2→1) branched chains. Due to its chemical properties, levan has possible applications in both the food and pharmaceutical industries. Bacillus subtilis is a promising industrial levan producer, as it ferments sucrose and has a high levan-formation capacity. A new strain of B. subtilis was recently isolated from Japanese food natto, and it has produced levan in large quantities. For future pharmaceutical applications, this study aimed to investigate the effects of levan produced by B. subtilis Natto, mainly as potential hypoglycemic agent, (previously optimized with a molecular weight equal to 72.37 and 4,146 kDa) in Wistar male rats with diabetes induced by streptozotocin and non-diabetic rats and to monitor their plasma cholesterol and triacylglycerol levels. After 15 days of experimentation, the animals were sacrificed, and their blood samples were analyzed. The results, compared using analysis of variance, demonstrated that for this type of levan, a hypoglycemic effect was not observed, as there was no improvement of diabetes symptoms during the experiment. However, levan did not affect any studied parameters in normal rats, indicating that the exopolysaccharide can be used for other purposes.

  3. Levan from Bacillus subtilis Natto: its effects in normal and in streptozotocin-diabetic rats

    Directory of Open Access Journals (Sweden)

    Fernando Cesar Bazani Cabral de Melo

    2012-12-01

    Full Text Available Levan is an exopolysaccharide of fructose primarily linked by β-(2→6 glycosidic bonds with some β-(2→1 branched chains. Due to its chemical properties, levan has possible applications in both the food and pharmaceutical industries. Bacillus subtilis is a promising industrial levan producer, as it ferments sucrose and has a high levan-formation capacity. A new strain of B. subtilis was recently isolated from Japanese food natto, and it has produced levan in large quantities. For future pharmaceutical applications, this study aimed to investigate the effects of levan produced by B. subtilis Natto, mainly as potential hypoglycemic agent, (previously optimized with a molecular weight equal to 72.37 and 4,146 kDa in Wistar male rats with diabetes induced by streptozotocin and non-diabetic rats and to monitor their plasma cholesterol and triacylglycerol levels. After 15 days of experimentation, the animals were sacrificed, and their blood samples were analyzed. The results, compared using analysis of variance, demonstrated that for this type of levan, a hypoglycemic effect was not observed, as there was no improvement of diabetes symptoms during the experiment. However, levan did not affect any studied parameters in normal rats, indicating that the exopolysaccharide can be used for other purposes.

  4. Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats

    Science.gov (United States)

    Fabricio, Victor; Oishi, Jorge Camargo; Biffe, Bruna Gabriele; Ruffoni, Leandro Dias Gonçalves; da Silva, Karina Ana; Nonaka, Keico Okino; Rodrigues, Gerson Jhonatan

    2017-01-01

    Background Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

  5. Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L; Reimers, J; Mandrup-Poulsen, T

    1991-01-01

    . An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1 beta. A single injection of rIL-1 beta caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 beta induced a diminished weight gain, a 24-28% reduction......Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance...... in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1 beta treated rats...

  6. Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.

    Science.gov (United States)

    Beaudin, Stéphane A; Stangle, Diane E; Smith, Donald R; Levitsky, David A; Strupp, Barbara J

    2007-01-01

    This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). In the RO task, the performance disruption produced by committing an error on the previous trial was significantly greater for both unchelated lead-exposed groups than for controls. The High Pb rats were also more sensitive to reward omission than controls, providing converging evidence for impaired regulation of arousal or emotion. Importantly, succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.

  7. Hypoglycemic activity of Bougainvillea spectabilis stem bark in normal and alloxan-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Sunil Jawla; Y Kumar; MSY Khan

    2012-01-01

    Objective: Bougainvillea spectabilis (B. spectabilis) is one of the main constituent of various herbal formulations available for diabetes. The aim of present study was to screen hypoglycemic potential of B. spectabilis stem bark extracts in albno rats (Wistar strain). Methods: The EtOH extracts (100, 250 and 500 mg/kg/day) of the B. spectabilis were administered to both normal and alloxan induced diabetic rats at defined time intervals. Blood glucose levels were measured at 0, 0.5, 1, 2, 4, 6 h, and on 0, 1, 3, 5, 7th day after oral administration of extracts. Of the doses test, highest anti-hyperglycemic effect was observed by the extract of stem bark at 250 mg/kg after a week treatment. Results: B. spectabilis stem bark extract exhibited significant hypoglycemic activity at different doses and intervals. Stem bark extract was found to be 22.2% more potent than standard oral hypoglycemic drug, glibenclamide 0.2 mg/kg. Conclusion: Treatment of alloxan induced diabetic rats up to a week with stem bark extract reversed the permanent hyperglycemia. Hence, B. spectabilis stem bark alcoholic extract exhibited potent hypoglycemic activity.

  8. MRI relaxation in the presence of fictitious fields correlates with myelin content in normal rat brain.

    Science.gov (United States)

    Hakkarainen, Hanne; Sierra, Alejandra; Mangia, Silvia; Garwood, Michael; Michaeli, Shalom; Gröhn, Olli; Liimatainen, Timo

    2016-01-01

    Brain myelin plays an important role in normal brain function. Demyelination is involved in many degenerative brain diseases, thus quantitative imaging of myelin has been under active investigation. In previous work, we demonstrated the capability of the method known as Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) to provide image contrast between white and gray matter in human and rat brains. Here, we provide evidence pointing to myelin being the major source of this contrast. RAFFn relaxation time constant (TRAFFn) was mapped in rat brain ex vivo. TRAFFn was quantified in 12 different brain areas. TRAFFn values were compared with multiple other MRI metrics (T1, T2 , continuous wave T1ρ, adiabatic T1ρ and T2ρ, magnetization transfer ratio), and with histologic measurements of cell density, myelin and iron content. Highest contrast between white and grey matter was obtained with TRAFFn in the rotating frames of ranks n = 4 and 5. TRAFFn values correlated strongly with myelin content, whereas no associations between TRAFFn and iron content or cell density were found. TRAFFn with n = 4 or 5 provides a high sensitivity for selective myelin mapping in the rat brain. © 2015 Wiley Periodicals, Inc.

  9. Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts.

    Science.gov (United States)

    Colombo, Gualtiero; Sordi, Andrea; Lonati, Caterina; Carlin, Andrea; Turcatti, Flavia; Leonardi, Patrizia; Gatti, Stefano; Catania, Anna

    2008-08-01

    Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium

  10. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    Science.gov (United States)

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  11. Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation.

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    Chloé A Picq

    Full Text Available Vagus nerve stimulation (VNS has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes' activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes.

  12. Effects of microcurrent stimulation on Hyaline cartilage repair in immature male rats (Rattus norvegicus

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    de Campos Ciccone Carla

    2013-01-01

    Full Text Available Abstract Background In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats. Methods Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis. Results Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35. Conclusion We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.

  13. Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats

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    Kurtz, A.; Zapf, J.; Eckardt, K.U.; Clemons, G.; Froesch, E.R.; Bauer, C. (Universitaet Zurich (Switzerland))

    1988-10-01

    Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. The authors have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 {mu}g of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, {sup 59}Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and {sup 59}Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.

  14. Effects of microcurrent stimulation on hyaline cartilage repair in immature male rats (Rattus norvegicus).

    Science.gov (United States)

    de Campos Ciccone, Carla; Zuzzi, Denise Cristina; Neves, Lia Mara Grosso; Mendonça, Josué Sampaio; Joazeiro, Paulo Pinto; Esquisatto, Marcelo Augusto Marretto

    2013-01-19

    In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats. Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis. Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35. We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.

  15. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  16. Normalization of visual evoked potentials using underlying electroencephalogram levels improves amplitude reproducibility in rats.

    Science.gov (United States)

    You, Yuyi; Thie, Johnson; Klistorner, Alexander; Gupta, Vivek K; Graham, Stuart L

    2012-03-15

    The visual evoked potential (VEP) is a frequently used noninvasive measurement of visual function. However, high-amplitude variability has limited its potential for evaluating axonal damage in both laboratory and clinical research. This study was conducted to improve the reliability of VEP amplitude measurement in rats by using electroencephalogram (EEG)-based signal correction. VEPs of Sprague-Dawley rats were recorded on three separate days within 2 weeks. The original VEP traces were normalized by EEG power spectrum, which was evaluated by Fourier transform. A comparison of intersession reproducibility and intersubject variability was made between the original and corrected signals. Corrected VEPs showed lower amplitude intersession within-subject SD (Sw), coefficient of variation (CoV), and repeatability (R(95)) than the original signals (P < 0.001). The intraclass correlation coefficient (ICC) of the corrected traces (0.90) was also better than the original potentials (0.82). For intersubject variability, the EEG-based normalization improved the CoV from 44.64% to 30.26%. A linear correlation was observed between the EEG level and the VEP amplitude (r = 0.71, P < 0.0001). Underlying EEG signals should be considered in measuring the VEP amplitude. In this study, a useful technique was developed for VEP data processing that could also be used for other cortical evoked potential recordings and for clinical VEP interpretation in humans.

  17. Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

    Science.gov (United States)

    Does, Mark D; Parsons, Edward C; Gore, John C

    2003-02-01

    Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

  18. Stimulation of in vitro triglyceride synthesis in the rat hepatocyte by growth hormone treatment in vivo.

    Science.gov (United States)

    Elam, M B; Simkevich, C P; Solomon, S S; Wilcox, H G; Heimberg, M

    1988-04-01

    Hepatic fatty acid metabolism in the rat is sexually differentiated. Rates of esterification by the liver of fatty acid into triglyceride and other esterification products (phospholipid, diglyceride, cholesteryl esters) are higher in the female than in the male. There is evidence to suggest that GH feminizes other hepatic systems that exhibit sexual dimorphism, including hepatic steroid metabolism, PRL receptors, and estrogen binding. To investigate the role of GH in maintenance of the high rates of fatty acid esterification observed in the female, we assessed rates of [1-14C]oleic acid utilization by hepatocytes prepared from hypophysectomized (hypox) cortisol/T3-replaced female rats with an without continuous in vivo infusion of human (h) GH (5 micrograms/h). In addition, we assessed the effect of in vivo hGH treatment (5 micrograms/h) on [1-14C]oleic acid utilization in the normal male rat. Hypophysectomy was accompanied by a reduction in incorporation of [1-14C]oleic acid into products of esterification (triglyceride, phospholipid, diglyceride) and oxidation (CO2, ketone bodies). Continuous infusion of hGH (5 micrograms/h; 14 days) restored rates of fatty acid esterification in the hypox-cortisol/T3-replaced female rat, with the exception of cholesteryl esters. hGH infusion partially restored rates of fatty acid oxidation in the hypox cortisol/T3-replaced female rat. Treatment of the adult male rat with continuous infusion of hGH (5 micrograms/h; 7 days) resulted in increased rates of incorporation of [1-14C] oleic acid into triglyceride. In contrast, incorporation of oleic acid into phospholipid, diglyceride, and cholesteryl esters was unaltered. These results suggest that GH may be an important regulator of hepatic fatty acid metabolism.

  19. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    Science.gov (United States)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  20. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats.

    Science.gov (United States)

    Pillay, Siveshigan; Vizuete, Jeannette; Liu, Xiping; Juhasz, Gabor; Hudetz, Anthony G

    2014-01-01

    States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA) and secondary visual (V2) cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5, 4.5, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness). Information integration was characterized by integration (multiinformation) and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 × 10(3) bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 × 10(3) bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.

  1. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats

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    Siveshigan ePillay

    2014-02-01

    Full Text Available States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA and secondary visual (V2 cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5%, 4.5%, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness. Information integration was characterized by integration (multiinformation and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 x103 bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 x103 bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.

  2. BOLD temporal dynamics of rat superior colliculus and lateral geniculate nucleus following short duration visual stimulation.

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    Condon Lau

    Full Text Available BACKGROUND: The superior colliculus (SC and lateral geniculate nucleus (LGN are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s visual stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION, a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK 0.2±0.2 s before the LGN signal (p<0.05. The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05. These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. CONCLUSIONS/SIGNIFICANCE: The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are

  3. Effects of Electrical Stimulation During Absolute Refractory Period on Contraction and Relaxation of Cardiomyocytes from Normal Guinea-pigs

    Institute of Scientific and Technical Information of China (English)

    赵晓静; 崔长琮; 张海柱

    2003-01-01

    Objectives To investi- gate the effect of electrical stimulation during absoluterefractory period on contraction and relaxation of ven-tricular myocytes from normal guinea-pigs. MethodsThe guinea -pig ventricular myocytes were obtainedby enzyme digesting, and the extent of its contractionand relaxation and Ca2+ transient were recordedthrough the motion edge detection system. Resultsmyocytes increased 15.45±6.48%, and the peakvelocity of shorting (contraction) and the peak velocity of relengthening (relaxation) increased 15.97±8.37% and 21.63 ± 8.06% respectively ( n = 10 );tio(360/380) (F360/F380) increased 22. 55 ± 9.08%,and the peak velocity of ventricular myocytes F360/F380 increased 36.75 ± 9.77% and 23.62 ± 4.47%during shorting and relengthening respectively (n =6) . Conclusions Appropriate electrical stimulationmay strengthen the contracting and relaxing function ofnormal guinea- pig ventricular myocytes.

  4. Histopathological Comparison of the Effect of Normal Saline and Silver Sulfadiazine on Scorch Healing in Rats

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    Daryoush Mohajeri

    2012-03-01

    Full Text Available Skin burn is one of the most common complications throughout the world. Silver sulfadiazine (SSD is used as a choice treatment in many superficial burn wounds. But, some studies have questioned its efficacy. The main objective of this study was to compare the effects of Normal Saline (NS and SSD on healing of superficial skin burn wounds in rats. Male Wistar rats were randomly assigned in two different groups including treatment and control, with 20 animals each. After sedation, a type II skin burn wound in the shape of a 1-cm diameter circle was created in the dorsum of the rats with boiled water contact. In treatment group, NS and in control group, SSD was used topically for care. Diameter of the wound as well as the hair growing grade was determined on days 3, 7 and 14 post-intervention. In each step of the experiment, histopathological sections were prepared; thereafter reepithelialization and alleviation of inflammation at the healing site of burn wound were assessed. Statistically, the data obtained were compared between the groups. There were no significant differences between the groups regarding the mean diameter of the wound on days 3 and 14 (p = 0.089, p = 0.495. The mean diameter of the wound was significantly lower in treatment (NS group on day 7 (p<0.001. There were no significant differences between the groups regarding the mean hair growth score in different stages of the experiment (p = 1, p = 0.647, p = 0.805. Histopathologically, there were no significant difference between these two experimental groups from the view point of reepithelialization and alleviation of inflammation at the healing site of burn wound. The results of this study showed that NS equals with SSD in improvement of superficial skin burn wounds healing in the rats; and after the randomized clinical trials, it can be used in treatment of superficial skin burn wounds in human bodies.

  5. Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

    Science.gov (United States)

    Jin, Hua; Teng, Yueqiu; Zhang, Xuexin; Yang, Chunxiao; Xu, Manying; Yang, Lizhuang

    2014-06-27

    Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

  6. Acupuncture at heterotopic acupoints facilitates distal colonic motility via activating M3 receptors and somatic afferent C-fibers in normal, constipated, or diarrhoeic rats.

    Science.gov (United States)

    Gao, X; Qin, Q; Yu, X; Liu, K; Li, L; Qiao, H; Zhu, B

    2015-12-01

    Previous studies have demonstrated the efficacy of somatic stimulation for patients with gastrointestinal motility disorders. However, little effort has been made to investigate the effects of acupuncture on colonic motility, particularly in pathological conditions. The precise mechanism employed in the regulation of acupuncture on colonic motility still remains unclear. We assessed the effect of acupuncture at heterotopic acupoints on distal colonic motility using a warm-water-filled manometric balloon inserted 5-6 cm into the rectum of anesthetized normal rats or rats with diarrhea or constipation. Choline chloride, 4-DAMP, cobra venom and capsaicin were separately applied to investigate the role of M3 receptors in the regulation of distal colonic motility by acupuncture at heterotopic acupoints, and whether Aδ- and/or C-fibers are required for triggering distal colonic motility by acupuncture. Acupuncture at heterotopic acupoints increased distal colonic motility not only in normal rats but also in rats with constipation or diarrhea. M3 receptors play an important role in the facilitation of distal colonic motility triggered by acupuncture at heterotopic acupoints. Afferent nerve Aδ- and C-fibers mediate the transduction of the acupuncture signal and C-fibers are essential for enhancing the effect of acupuncture at the heterotopic acupoint on distal colonic motility. Our results reveal that acupuncture at heterotopic acupoints increases distal colonic motility regardless of normal or pathological conditions via predominately activating C-fibers of somatic afferent nerve and M3 receptors. © 2015 The Authors.Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

  7. Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice.

    Science.gov (United States)

    Song, Mingke; Yu, Shan Ping; Mohamad, Osama; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Jiang, Michael Qize; Wei, Ling

    2017-02-01

    Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain. In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release into SVZ region, evoked membrane currents, Ca(2+) influx and increased proliferation of SVZ neuroblasts, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum started 5days after stroke for 8days not only promoted cell proliferation but also the migration of SVZ neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ neuronal regulation via a semi-phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery. The benefits from stimulating endogenous glutamatergic activity suggest a novel regenerative strategy after ischemic stroke and other brain injuries.

  8. Parathyroid hormone stimulating synthesis of fibronectin by mesangial cells via TGF-β in rats

    Institute of Scientific and Technical Information of China (English)

    ZHAN Feng-lan; YUAN Wei-jie; MEI Xiao-bin; WU Hao; XU Jing; LIU Yu-Jian; LU Jian

    2002-01-01

    Objective: To investigate whether hPTH1-34 regulate the synthesis of fibronectin (FN) from cultured rat mesangial cells and its possible mechanism. Methods: (1) MCs seeded at a density of 1 × 104 per well in 24-well plates were treated with medium containing various concentrations of hPTH1-34 (10-12 mol/l-10-8 mol/l) for 6 h, 12 h, 24 h and 48 h, control cells were treated with vehicle only. The FN levels (in the supernatant) were measured by ELISA assay. (2) MCs were co-cultured with 10 ng/l of anti-TGF-β antibody and various concentrations of hPTH1-34 (10-12 mol/l-10-8 mol/l ). Forty-eight hours later, FN were tested by ELISA. (4) MCs were co-cultured with 10 ng/l of anti-TGF-β antibody and 10-8 mol/l hPTH1-34 for 6 h, 12 h, 24 h and 48 h and then FN were tested. Results: (1) hPTH1-34 stimulated FN synthesis in a doseand time-dependent way with a peak at 10-8 mol/l (P<0.01). (2) Anti-TGF-β antibody inhibited the stimulation effect of hPTH1-34 on synthesis of FN in cultured rat mesangial cells (P<0. 05). Conclusion: hPTH1-34up-regulates FN synthesis in cultured rat mesangial cells via TGF-β, suggesting that PTH may play an important role in deteriorating the residual renal function at the early stage of chronic renal disease.

  9. Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells

    Science.gov (United States)

    Jiménez-Palomares, Margarita; López-Acosta, José Francisco; Villa-Pérez, Pablo; Moreno-Amador, José Luis; Muñoz-Barrera, Jennifer; Fernández-Luis, Sara; Heras-Pozas, Blanca; Perdomo, Germán; Bernal-Mizrachi, Ernesto

    2015-01-01

    Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation. We hypothesized that cyclin C overexpression would induce β-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional β-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [3H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected β-cell death by TUNEL, β-cell differentiation by RT-PCR, and β-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human β-cell proliferation. This augmented proliferation did not induce β-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing β-cell regeneration. PMID:25564474

  10. Neonatal tactile stimulation changes anxiety-like behavior and improves responsiveness of rats to diazepam.

    Science.gov (United States)

    Boufleur, Nardeli; Antoniazzi, Caren T D; Pase, Camila S; Benvegnú, Dalila M; Barcelos, Raquel C S; Dolci, Geisa S; Dias, Verônica T; Roversi, Katiane; Roversi, Karine; Koakoskia, Gessi; Rosa, João G; Barcellos, Leonardo J G; Bürger, Marilise E

    2012-09-20

    In this study we evaluated the influence of neonatal tactile stimulation (TS) on behavioral and biochemical effects related to a low dose of diazepam (DZP) in adult rats. Male pups of Wistar rats were handled (TS) daily from PND1 to PND21 for 10 min, while unhandled (UH) rats were not touched. In adulthood, half the animals of each group received a single administration of diazepam (0.25mg/kg body weight i.p.) or vehicle and then were submitted to behavioral and biochemical evaluations. In the TS group, DZP administration reduced anxiety-like symptoms in different behavioral paradigms (elevated plus maze, EPM; staircase and open-field and defensive burying) and increased exploratory behavior. These findings show that neonatal TS increased DZP pharmacological responses in adulthood compared to neonatally UH animals, as observed by reduced anxiety-like symptoms and lower levels of plasma cortisol. TS also changed plasma levels of antioxidant defenses such as vitamin C and glutathione peroxidase, whose increase may be involved in lower oxidative damages to proteins in cortex, subthalamic region and hippocampus of these animals. Here we are showing for the first time that neonatal TS is able to change responsiveness to benzodiazepine drugs in adulthood and provides better pharmacological responses in novel situations of stress.

  11. Effects of subconvulsive electrical stimulation to the hippocampus on emotionality and spatial learning and memory in rats

    Institute of Scientific and Technical Information of China (English)

    王庆松; 王正国; 朱佩芳; 蒋建新

    2003-01-01

    Objective To observe the effects of repeated subconvulsive electrical stimuli to the hippocampus on the emotional behavior and spatial learning and memory ability in rats.Methods One hundred and eight male Wistar rats were randomized into 3 groups. Animals in group SE (n=42) were given subconvulsive electrical stimulation to the hippocampus through a constant pulsating current of 100 μA with an intratrain frequency of 25 Hz, pulse duration of 1 millisecond, train duration of 10 seconds and interstimulus interval of 7 minutes, 8 times a day, for 5 days. In the electrode control group or CE group (n=33), animals were implanted with an electrode in the hippocampus, but were not stimulated. Group NC (n=33) animals received no electrode or any stimulation. The emotional behavior of experimental rats was examined by activity in an unfamiliar open field and resistance to capture from the open field, while the spatial learning and memory ability was measured during training in a Morris water maze.Results The stimulated rats tested 1 month after the last round of stimulation displayed substantial decreases in open field activity (scale: 10.4±2.3, P<0.05) and increases in resistance to capture (scale: 2.85±0.56, P<0.01). The amount of time for rats in group SE to find the platform (latency) as a measurement for spatial bias was prolonged (29±7) seconds after 15 trials in the water maze, P<0.05). The experimental rats swam aimlessly in all four pool quadrants during the probe trial in the Morris water maze.Conclusions Following repeated subconvulsive electrical stimuli to the hippocampus, rats displayed long-lasting significant abnormalities in emotional behavior, increased anxiety and defensiveness, enhanced ease to and delayed habituation to startlement, transitory spatial learning and memory disorder, which parallels many of the symptoms in posttraumatic stress disorder patients.

  12. Differences in antiepileptic drug efficacy in hippocampally kindled normal and microcephalic rats.

    Science.gov (United States)

    Majkowski, J; Danneberg, P; Knappen, F; Sersen, E A

    1986-10-29

    The difference in antiepileptic drug efficacy was investigated in two groups of animals: 5 normal and 4 microcephalic rats. The latter were produced by a single i.p. injection of 30 mg/kg methylazoxymethanol acetate in the mother on the 15th day of gestation. Hippocampal kindling was performed to a seizure criterion in all animals followed by testing of the antiepileptic drugs vs placebo. Besides carbamazepine (CBZ), two new anticonvulsants were tested: (E)-2-[(alpha-amino)phenylmethylene]-benzo-[b]-thiophene-3(2H)-one (AF-CX 921) and its metabolite (E)-2-[alpha-amino)phenylmethylene]-benzo-[b]-thiophene-3(2H)-one- 1- oxide (AF-CX 1325). Frequency of occurrence and duration of afterdischarges and seizures were statistically examined. The duration of early afterdischarges (AD1) tended to be shorter in microcephalic than in normal animals in control and placebo periods. In contrast, during treatment with the antiepileptic drugs, AD1 durations were longer in microcephalic than in normal animals. This suggests that the drugs inhibited AD1 to a lesser extent in the microcephalics. Two other characteristics of EEG epileptic activity, focal spiking (FS) and late afterdischarges (AD2) also varied in the two groups. Both were significantly lower in occurrence in the microcephalic rats independent of treatment. Three types of behavioral manifestations were also examined: convulsive seizures (CS), epileptic behavior (EB) and quiet states (Q). The two groups of animals responded differently to the drugs with respect to Q and CS. In the microcephalics, AFCX 1325 and AFCX 921 were superior to CBZ, which in turn, was superior to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Directory of Open Access Journals (Sweden)

    Anna Kubesova

    Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  14. Stimulation site determines the conditioned effects of kindling in rats: anterior neocortex versus amygdala.

    Science.gov (United States)

    Barnes, Steven J; Pinel, John P J; Wig, Gagan S; Stuettgen, Maik C; Hölzel, C Heike

    2003-04-01

    Rats received 53 stimulations to either the left basolateral amygdala (BA) or left anterior neocortex (AN) in one environment (CS+) and 53 sham stimulations (the stimulation lead was attached but no current was delivered) in another environment (CS-), quasirandomly over 54 days. Confirming a previous report [Barnes, S.J., Pinel, J.P., Francis, L.H. & Wig, G.S. (2001) Behav. Neurosci., 115, 1065-1072], as BA kindling progressed, the CS+ began to elicit more defensive behaviours (i.e. less activity, more freezing and avoidance of the CS+) than the CS-, and at the end of the experiment, convulsions elicited in the CS+ were more severe than those elicited in the CS-. Like BA kindling, AN kindling led to less activity in the CS+; but unlike BA kindling, AN kindling led to more wet-dog-shakes and less, rather than more, severe convulsions in the CS+. During AN kindling, the mean number of wet-dog-shakes in the CS+ was negatively correlated with the mean convulsion class, suggesting that wet-dog-shakes contribute to the inherent variability of AN kindling. These findings confirm that inherent conditioned effects influence kindled convulsions and interictal behaviour and establish for the first time that the pattern of these conditioned effects is a function of the kindling site.

  15. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Science.gov (United States)

    Kubesova, Anna; Tejkalova, Hana; Syslova, Kamila; Kacer, Petr; Vondrousova, Jana; Tyls, Filip; Fujakova, Michaela; Palenicek, Tomas; Horacek, Jiri

    2015-01-01

    Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease). The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin), their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  16. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    Science.gov (United States)

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  17. Laser stimulation of the acupoint 'Zusanli' (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

    Science.gov (United States)

    Frederico, Éric H F F; Santos, Ailton A; Sá-Caputo, Danubia C C; Neves, Rosane F; Guimarães, Carlos A S; Chang, Shyang; Bernardo-Filho, Mario

    2016-03-01

    Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the 'Zusanli' acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na(99m)TcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm(2)) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na(99m)TcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

  18. Plasticity in the rat posterior auditory field following nucleus basalis stimulation.

    Science.gov (United States)

    Puckett, Amanda C; Pandya, Pritesh K; Moucha, Raluca; Dai, WeiWei; Kilgard, Michael P

    2007-07-01

    Classical conditioning paradigms have been shown to cause frequency-specific plasticity in both primary and secondary cortical areas. Previous research demonstrated that repeated pairing of nucleus basalis (NB) stimulation with a tone results in plasticity in primary auditory cortex (A1), mimicking the changes observed after classical conditioning. However, few studies have documented the effects of similar paradigms in secondary cortical areas. The purpose of this study was to quantify plasticity in the posterior auditory field (PAF) of the rat after NB stimulation paired with a high-frequency tone. NB-tone pairing increased the frequency selectivity of PAF sites activated by the paired tone. This frequency-specific receptive field size narrowing led to a reorganization of PAF such that responses to low- and mid-frequency tones were reduced by 40%. Plasticity in A1 was consistent with previous studies -- pairing a high-frequency tone with NB stimulation expanded the high-frequency region of the frequency map. Receptive field sizes did not change, but characteristic frequencies in A1 were shifted after NB-tone pairing. These results demonstrate that experience-dependent plasticity can take different forms in both A1 and secondary auditory cortex.

  19. FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells.

    Science.gov (United States)

    Gualtieri, Ariel F; Mazzone, Graciela L; Rey, Rodolfo A; Schteingart, Helena F

    2009-06-01

    Migration of developing germ cells from the basal to the adluminal compartment of the seminiferous epithelium requires extensive tissue restructuring, resulting in the production of reactive oxygen species. Sertoli cells are involved in this process. Glutathione (GSH), produced by Sertoli cells, has an essential role in cell protection against oxidative stress. Intracellular GSH content is maintained by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation increased Sertoli cell GSH levels after 24 h incubation. The simultaneous addition of FSH and bFGF did not produce any further effect. GCLM expression was upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still observed. FSH and bFGF also upregulated GR expression. In conclusion, our results show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation of the de novo synthesis and recycling by upregulating GCLM and GR expression respectively. Therefore, protection of germ cells against oxidative stress seems to be regulated by hormones and germ cell-released growth factors capable of influencing the production of Sertoli cell GSH.

  20. Miniaturized neural sensing and optogenetic stimulation system for behavioral studies in the rat

    Science.gov (United States)

    Kim, Min Hyuck; Nam, Ilho; Ryu, Youngki; Wellman, Laurie W.; Sanford, Larry D.; Yoon, Hargsoon

    2015-04-01

    Real time sensing of localized electrophysiological and neurochemical signals associated with spontaneous and evoked neural activity is critically important for understanding neural networks in the brain. Our goal is to enhance the functionality and flexibility of a neural sensing and stimulation system for the observation of brain activity that will enable better understanding from the level of individual cells to that of global structures. We have thus developed a miniaturized electronic system for in-vivo neurotransmitter sensing and optogenetic stimulation amenable to behavioral studies in the rat. The system contains a potentiostat, a data acquisition unit, a control unit, and a wireless data transfer unit. For the potentiostat, we applied embedded op-amps to build single potential amperometry for electrochemical sensing of dopamine. A light emitting diode is controlled by a microcontroller and pulse width modulation utilized to control optogenetic stimulation within a sub-millisecond level. In addition, this proto-typed electronic system contains a Bluetooth module for wireless data communication. In the future, an application-specific integrated circuit (ASIC) will be designed for further miniaturization of the system.

  1. Long-term depression and associativity in rat primary motor cortex following thalamic stimulation.

    Science.gov (United States)

    Eckert, M J; Racine, R J

    2006-12-01

    Associativity is an attractive property of LTP in terms of its possible mechanism as a model for memory storage. In this study, we compare the effects of homosynaptic vs. associative stimulation on the induction of LTP and LTD in the neocortex of freely behaving rats. Using a callosal input to the motor cortex as a 'strong' input (one that potentiates reliably following homosynaptic stimulation), we paired activity of this pathway with a 'weak' thalamocortical pathway (one that does not potentiate when stimulated homosynaptically). Surprisingly, homosynaptic HFS caused a lasting depression of the field EPSP in the thalamocortical pathway. Analysis of this effect revealed that it was largely polysynaptic. Associative HFS (HFS applied to both pathways) not only failed to induce an LTP effect in the thalamocortical pathway, it increased the magnitude of the depression. Associative HFS did, however, facilitate LTP induction in the 'strong' callosal pathway. When comparing the effects of homosynaptic and associative LTD induction (HFS on one pathway anticorrelated with LFS on the other), we found that both protocols induced a similar magnitude of depression. These results show that HFS applied to the thalamocortical pathway causes a depression and this depression is enhanced, not reversed, by associative pairing with a strong input.

  2. Cutaneous responsiveness of rat single motor units activated by natural stimulation.

    Science.gov (United States)

    Solano, R; Herrero, J F

    1997-05-16

    Recordings of withdrawal reflexes have been used extensively to study sensory-motor integration and processing of nociceptive information in the spinal cord. We describe here a new technique for the manufacture of improved EMG electrodes that permit the characterisation of the physiological properties of single motor units as well as the easy location of the muscles studied. Individual motor units from three rat hind-limb muscles: peroneus longus, tibialis cranialis and extensor digitorum longus, were activated by thermal and mechanical stimulation applied to their cutaneous receptive fields, which were located mainly on the 4th and 5th toes. Thresholds for thermal and mechanical (Von Frey hairs) stimulation were similar in the three muscles studied, with a value of 44 +/- 1 degrees C and 100 mN (median), respectively. However, when a mechanical pincher with a stimulus area of 14 mm2 was used, the values seen were similar for peroneus longus and tibialis cranialis (342 +/- 23 and 330 +/- 71 mN, respectively, mean +/- S.E.M.) but lower for extensor digitorum longus (220 +/- 37 mN, mean +/- S.E.M.). The firing rate of the single motor units was similar for all types of stimulation at threshold intensity, and showed a linear relationship with stimulus intensity, except for units of the tibialis cranialis, which showed a greater degree of adaptation.

  3. Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ.

    Directory of Open Access Journals (Sweden)

    Hanibal Hani Adamo

    Full Text Available Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, ≥2-fold change in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could

  4. Anti-apoptotic effects of recombinant human granulocyte colony-stimulating factor in focal cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    Xia Yuan; Shiming Zhang; Wanli Dong; Qi Fang

    2011-01-01

    The neuroprotective effects of granulocyte colony-stimulating factor in cerebral ischemia/reperfusion injury are currently contentious. The present study examined the effects of subcutaneous injection of recombinant human granulocyte colony-stimulating factor (50 μg/kg) over 5 days in a model of cerebral ischemia/reperfusion with intraluminal filament occlusion in rats. The results indicated that recombinant human granulocyte colony-stimulating factor reduced brain infarct volume following cerebral ischemia/reperfusion injury in rats, down-regulated the expression of caspase-3 mRNA (a key protease for apoptosis in the cerebral ischemia zone), lowered the rate of neuronal apoptosis in the cerebral ischemia zone, and notably ameliorated neurological function. These results indicate that recombinant human granulocyte colony-stimulating factor has anti-apoptotic effects on neurons following focal cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

  5. Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

    OpenAIRE

    2008-01-01

    In this study, we compared the depression–like symptoms induced by olfactory bulbectomy (OBX) in the two inbred Wistar and Long Evans rat strains. We also analyzed the self-regulated oral intake of nicotine in these strains and the effect of nicotine on the depression-like symptoms of olfactory bulbectomy. Furthermore, we compared the antidepressant-like effects of nicotine on Wistar rats to those of transcranial magnetic stimulation (TMS), which has emerged as a therapeutic alternative for d...

  6. Cultured rat and purified human Pneumocystis carinii stimulate intra- but not extracellular free radical production in human neutrophils

    DEFF Research Database (Denmark)

    Jensen, T; Aliouat, E M; Lundgren, B

    1998-01-01

    The production of free radicals in human neutrophils was studied in both Pneumocystis carinii derived from cultures of L2 rat lung epithelial-like cells and Pneumocystis carinii purified from human lung. Using the cytochrome C technique, which selectively measured extracellular superoxide....... It was established that 1) P. carinii stimulated intra- but not extracellular free radical production in human neutrophils, 2) opsonized cultured rat-derived P. carinii stimulated human neutrophils to a strong intracellular response of superoxide production, and 3) opsonized P. carinii, purified from human lung also...

  7. Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats

    Directory of Open Access Journals (Sweden)

    Priyadarshani Anjali

    2010-04-01

    Full Text Available Abstract Background Noscapine, an alkaloid from Papaver somniferum, widely used as an antitussive, is being clinically studied in the treatment of polycystic ovary syndrome (PCOS and a few other cancers primarily because of its anti-angiogenesis properties. With the advent of diverse application of noscapine, we sought to determine whether the radiolabeling method can be useful in studying uptake and kinetics of the molecule in-vivo. Specific objectives of this study were to radiolabel noscapine with Technetium-99m (Tc-99m, to determine its organ biodistribution in rat model and study its uptake kinetics in PCOS model. Methods A method for radiolabeling noscapine with Tc-99m was standardized using stannous reduction method and its in vitro and in vivo stability parameters were studied. The radiopharmaceutical was also evaluated for blood kinetics and biodistribution profile. An animal model of PCOS was created by using antiprogesterone RU486 and uptake of 99mTc-noscapine in normal and PCOS ovaries was compared using gamma scintigraphy. Results Noscapine hydrochloride was successfully radiolabeled with Tc-99m with high labeling efficiency and in vitro stability. Most of the blood clearance of the drug (80% took place in first hour after intravascular injection with maximum accumulation being observed in liver, spleen, kidney followed by the ovary. At 4 hours post injection, radiolabeled complex accumulation doubled in PCOS ovaries in rats (0.9 ± 0.03% ID/whole organ compared to normal cyclic rats (0.53 ± 0.01% ID/whole organ. This observation was further strengthened by scintigraphic images of rats taken at different time intervals (1 h, 2 h, 4 h, and 24 h where SPECT images suggested discrete accumulation in the PCOS ovaries. Conclusion Through our study we report direct radiolabeling of noscapine and its biodistribution in various organs and specific uptake in PCOS that may show its utility for imaging ovarian pathology. The increased ovarian

  8. Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation.

    Science.gov (United States)

    Lapi, D; Colantuoni, A; Del Seppia, C; Ghione, S; Tonlorenzi, D; Brunelli, M; Scuri, R

    2013-03-01

    The trigemino-cardiac reflex is a brainstem reflex known to lead to a decrement in heart rate and blood pressure, whereas few data have been collected about its effects on the cerebral hemodynamic. In this study we assess the in vivo effects of trigeminal nerve peripheral stimulation by mandibular extension on pial microcirculation and systemic arterial blood pressure in rats. Experiments were performed in male Wistar rats subjected to mandibular extension obtained inserting an ad hoc developed retractor between the dental arches. Mean arterial blood pressure and heart rate were recorded and the pial arterioles were visualized by fluorescence microscopy to measure the vessel diameters before (15 minutes) during (5-15 minutes) and after (80 minutes) mandibular extension. While in control rats (sham-operated rats) and in rats subjected to the dissection of the trigeminal peripheral branches mean arterial blood pressure, heart rate and pial microcirculation did not change during the whole observation period (110 minutes), in rats submitted to mandibular extension, mean arterial blood pressure, heart rate and arteriolar diameter significantly decreased during stimulation. Afterward mean arterial blood pressure remained reduced as well as heart rate, while arteriolar diameter significantly increased evidencing a vasodilatation persisting for the whole remaining observation time. Therefore, trigeminal nerve proprioceptive stimulation appears to trigger specific mechanisms regulating systemic arterial blood pressure and pial microcirculation.

  9. Joint feedback analysis modeling of nonesterified fatty acids in obese Zucker rats and normal Sprague-Dawley rats after different routes of administration of nicotinic acid.

    Science.gov (United States)

    Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

    2014-08-01

    Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague-Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague-Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration-response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the "degree of disease" can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Joint Feedback Analysis Modeling of Nonesterified Fatty Acids in Obese Zucker Rats and Normal Sprague–Dawley Rats after Different Routes of Administration of Nicotinic Acid

    Science.gov (United States)

    Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

    2014-01-01

    Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague–Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague–Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration–response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the “degree of disease” can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2571–2584, 2014 PMID:24986056

  11. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  12. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

    Science.gov (United States)

    Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.

    2017-01-01

    Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. PMID:28188129

  13. Salivary stimulation by prolonged release of pilocarpine using films in diabetic rats.

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    Jesús Rodríguez

    2015-04-01

    Full Text Available Introduction: The local use of prolonged drug delivery in the oral cavity provides many advantages, i.e., it increases pharmacologic actions in the desired local site, allows smaller doses and reduces adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for treating glandular hypofunction; however, the adverse effects associated with it limit its use. Objective: To evaluate cytotoxicity of films in adherent fibroblasts and their ability to release pilocarpine in vivo for a prolonged time in the oral cavity of diabetic rats and its effect on salivary flow.Methods: Chitosan and Hydroxypropylmethylcellulose (Methocel K4MCR films were prepared in 1% acetic acid and pilocarpine was added under magnetic stirring. Cytotoxicity of films was evaluated in adherent fibroblasts HS27 and assessed by neutral red technique. The sialogogue effect of films was evaluated on the floor of the mouth of diabetic rats. Later, histopathological analysis was performed using hematoxylin and eosin and Masson’s trichrome stains. Results: Films were biocompatible and had 96% cell viability. It was possible to increase stimulation of salivary flow in diabetic rats (6.36±0.987mg/hr compared to the control group (0.5±0.06mg/hr. The histopathological analysis did not show inflammatory infiltrate in the area where films were placed. Conclusion: Films were biocompatible and had high cell viability. Also, they considerably increased salivary flow in diabetic rats, without triggering an inflammatory infiltrate in the area which indicates that it is a biocompatible product for sustained release and safe for pilocarpine administration.

  14. The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation.

    Science.gov (United States)

    Lekhooa, Makhotso Rose; Walubo, Andrew; du Plessis, Jan B; Matsabisa, Motlalepula Gilbert

    2017-07-12

    separately for each drug induced immunosuppression. The immune system was monitored by observing for changes in plasma profiles of IL-2, IL-10, IgG, IgM, CD4 and CD8 cell counts at appropriate intervals, while in addition to function tests, the kidneys, liver, spleen, thymus, were weighed and examined for any pathology. The chromatographic fingerprint certified this batch of Phela as similar to the authentic Phela. There was no significant interaction between Phela and CsA, CP and Dex. The effective dose of Phela was determined to be 15.4mg/kg/day. Phela led to a moderate increase in the immune parameters in the normal rats. Co-administration of Phela 15mg/kg/day orally for 21 days with CsA led to stoppage and reversal of the immunosppressive effects of CsA that were exhibited as increased IL-2, IL-10, CD4 and CD8 counts, implying that Phela stimulates the cell mediate immunity (CMI). For CP, Phela led to stoppage and reversal, though moderate, of CP-induced suppression of IL-10, IgM and IgG only, implying that Phela stimulates the humoral immunity (HI) too. Phela had no effect on Dex induced immunosuppression. Stimulation of the CMI means that Phela clinical testing programme should focus on diseases or disorders that compromise the CMI, e.g., HIV and TB. The stimulation of the HI immunity means that Phela may stimulate existing memory cells to produce antibodies. The present study has revealed Phela's mechanism of action as mainly by stimulation of the CMI, implying that the use of Phela as immune booster in HIV patients is appropriate; and that using Phela as the test product, a rat model for screening medicinal products for immune stimulation has been successfully developed and validated, with a hope that it will lead to the testing of other related medicinal products. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  15. Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in the rat hippocampus but not spatial memory.

    Science.gov (United States)

    Zheng, Yiwen; Geddes, Lisa; Sato, Go; Stiles, Lucy; Darlington, Cynthia L; Smith, Paul F

    2014-05-01

    Galvanic vestibular stimulation (GVS) is a method of activating the peripheral vestibular system using direct current that is widely employed in clinical neurological testing. Since movement is recognized to stimulate hippocampal neurogenesis and movement is impossible without activation of the vestibular system, we speculated that activating the vestibular system in rats while minimizing movement, by delivering GVS under anesthesia, would affect hippocampal cell proliferation and neurogenesis, and spatial memory. Compared with the sham control group, the number of cells incorporating the DNA replication marker, bromodeoxyuridine (BrdU), was significantly reduced in the bilateral hippocampi in both the cathode left-anode right and cathode right-anode left stimulation groups (P ≤ 0.0001). The majority of the BrdU(+ve) cells co-expressed Ki-67, a marker for the S phase of the cell cycle, suggesting that these BrdU(+ve) cells were still in the cell cycle; however, there was no significant difference in the degree of co-labeling between the two stimulation groups. Single labeling for doublecortin (DCX), a marker of immature neurons, showed that while there was no significant difference between the different groups in the number of DCX(+ve) cells in the right dentate gryus, in the left dentate gyrus there was a significant decrease in the cathode left-anode right group compared with the sham controls (P ≤ 0.03). Nonetheless, when animals were tested in place recognition, object exploration and Morris water maze tasks, there were no significant differences between the GVS groups and the sham controls. These results suggest that GVS can have striking effects on cell proliferation and possibly neurogenesis in the hippocampus, without affecting spatial memory.

  16. AICAR stimulation metabolome widely mimics electrical contraction in isolated rat epitrochlearis muscle.

    Science.gov (United States)

    Miyamoto, Licht; Egawa, Tatsuro; Oshima, Rieko; Kurogi, Eriko; Tomida, Yosuke; Tsuchiya, Koichiro; Hayashi, Tatsuya

    2013-12-15

    Physical exercise has potent therapeutic and preventive effects against metabolic disorders. A number of studies have suggested that 5'-AMP-activated protein kinase (AMPK) plays a pivotal role in regulating carbohydrate and lipid metabolism in contracting skeletal muscles, while several genetically manipulated animal models revealed the significance of AMPK-independent pathways. To elucidate significance of AMPK and AMPK-independent signals in contracting skeletal muscles, we conducted a metabolomic analysis that compared the metabolic effects of 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) stimulation with the electrical contraction ex vivo in isolated rat epitrochlearis muscles, in which both α1- and α2-isoforms of AMPK and glucose uptake were equally activated. The metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry detected 184 peaks and successfully annotated 132 small molecules. AICAR stimulation exhibited high similarity to the electrical contraction in overall metabolites. Principal component analysis (PCA) demonstrated that the major principal component characterized common effects whereas the minor principal component distinguished the difference. PCA and a factor analysis suggested a substantial change in redox status as a result of AMPK activation. We also found a decrease in reduced glutathione levels in both AICAR-stimulated and contracting muscles. The muscle contraction-evoked influences related to the metabolism of amino acids, in particular, aspartate, alanine, or lysine, are supposed to be independent of AMPK activation. Our results substantiate the significance of AMPK activation in contracting skeletal muscles and provide novel evidence that AICAR stimulation closely mimics the metabolomic changes in the contracting skeletal muscles.

  17. Effect of esophageal distention on basal and stimulated gastric acid secretion in rats

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    Mohammad Kazem Gharib Nasery

    2007-02-01

    Full Text Available Background: It is well established that the esophageal distention leads to gastric relaxation, partly by vago-vagal reflex but till now, the effect of esophageal distention on gastric acid secretion has not been investigated. The aim of this study was to investigate the effect of esophageal distention (ED on basal and stimulated gastric acid secretion. Methods: Adult male Wistar rats (200-240g were deprived of food but not water for 24 hrs before the experiments. Under urethane anesthesia (1.2 g/kg, i.p., animals underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through duodenum for gastric distention and gastric washout and the esophagus was cannulated with a distensible balloon orally to distend esophagus (0.3 ml, 10 min. Gastric acid secretion was stimulated by gastric distention, carbachol (4 µg/kg, i.p. or histamine (5 mg/kg, s.c.. Effects of vagotomy, L-NAME (10 mg/kg, i.v., L-arginine (500 mg/kg, i.p. and hexamethonium were also investigated. Results: Esophageal distention reduces basal and gastric distention, carbachol and histamine stimulated acid secretion (P<0.05, P<0.0001, P<0.01 and P<0.02, respectively. Vagotomy reduced the inhibitory effect of the esophagus distention on gastric distention-induced acid secretion (P<0.05. Conclusion: These results indicate that vagus nerve involves in the inhibitory effect of the esophageal distention on the basal and stimulated gastric acid secretion. Nitric oxide (NO may also be involved.

  18. The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes.

    Science.gov (United States)

    Westhaus, Adrian; Blumrich, Eva Maria; Dringen, Ralf

    2017-01-01

    Metformin is the most frequently used drug for the treatment of type 2 diabetes in humans. However, only little is known about effects of metformin on brain metabolism. To investigate potential metabolic consequences of an exposure of brain cells to metformin, we incubated rat astrocyte-rich primary cultures with this compound. Metformin in concentrations of up to 30 mM did not acutely compromise the viability of astrocytes, but caused a time- and concentration-dependent increase in cellular glucose consumption and lactate production. For acute incubations in the hour range, the presence of 10 mM metformin doubled the glycolytic flux, while already 1 mM metformin doubled glycolytic flux during incubation for 24 h. In addition to metformin, also other guanidino compounds increased astrocytic lactate production. After 4 h of incubation, half-maximal stimulation of glycolysis was observed for metformin, guanidine and phenformin at concentrations of around 3 mM, 3 mM and 30 µM, respectively. The acute stimulation of glycolytic lactate production by metformin was persistent after removal of extracellular metformin and was also observed, if glucose was absent from the incubation medium or replaced by other hexoses. The metformin-induced stimulation of glycolytic flux was not prevented by compound C, an inhibitor of AMP-dependent protein kinase, nor was it additive to the stimulation of glycolytic flux caused by respiratory chain inhibitors. These data demonstrate that the antidiabetic drug metformin has the potential to strongly activate glycolytic lactate production in brain astrocytes.

  19. Antidiabetic effects of dendropanoxide from leaves of Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Moon, Hyung-In

    2011-08-01

    The present study evaluated the antidiabetic effect of Dendropanoxide (DP) from Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats. DP in the streptozotocin-induced diabetic rats showed significant hypoglycemic activity for 14 days significantly decreased the serum glucose, total cholesterol, triglycerides, urea, uric acid, creatinine, aspartate amino transferase (AST) and alanine amino transferase (ALT) while it increased the serum insulin in diabetic rats but not in normal rats (p < 0.05; at doses of 30, 60 and 100 mg/kg for 14 days). A comparison was made between the action of DP and glibenclamide (600 μg/kg), a known antidiabetic drug. The antidiabetic effect of the DP was more effective than that observed with glibenclamide.

  20. Competition between copper and silver in Fischer rats with a normal copper metabolism and in Long-Evans Cinnamon rats with an abnormal copper metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, N.; Sugawara, C. [Sapporo Medical Univ. (Japan). Dept. of Public Health

    2000-07-01

    Long-Evans Cinnamon (LEC) rats inherently lacking in serum ceruloplasmin (CP) activity and biliary Cu excretion were established from a closed colony of Long-Evans rats. These deficiencies, linked to a dysfunction of P-type ATPase, stimulate deposition of Cu and then of Cu metallothionein (MT) in the liver. Male LEC and Fischer rats were injected subcutaneously with Ag (AgNO{sub 3}), which is an antagonist to Cu. They were operated on 24 h after the injection while under anesthesia. Total uptake of Ag into the liver was not stimulated, but its uptake into the MT fraction increased significantly in the LEC rats. Ag injection notably decreased the activity of serum CP in the Fischer rats, but not in the LEC rats. The decrease was accompanied by a reduction of serum Cu. In Fischer rat serum treated with Ag, Ag was detected mainly in the albumin region and partly in the CP fraction. In LEC rat serum, however, the Ag concentration was about 1/20 of that in the Fischer rats, and Ag was not detected in the CP fraction. Ag injection decreased the biliary excretion of Cu in the Fischer rats (0.183-0.052 {mu}g Cu/20 min sampling), but not in the LEC rats (0.014-0.014 {mu}g Cu/20 min sampling). On the other hand, biliary excretion of Ag was much greater in the Fischer rats (1.25 {mu}g Ag/20 min) than in the LEC rats (0.04 {mu}g Ag/20 min). Our results suggest that uptake of Ag into the liver is not dependent on the hepatic Cu content and status, but that biliary excretion of Ag from the liver is affected by these. Hepatic MT is not a transporter of hepatobiliary excretion of Cu and Ag. It seems likely that, unlike Cu excretion, Ag is excreted by not only the CP route but also by another route into the serum. Ag may compete with Cu in the uptake into CP (conversion of apo-CP to holo-CP). (orig.)

  1. A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats.

    Science.gov (United States)

    Pei, Ming; Li, Jingting; McConda, David B; Wen, Sijin; Clovis, Nina B; Danley, Suzanne S

    2015-09-01

    Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly(lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici's collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats.

  2. Topical application of 1% ZnSO4 on oral ulcers increases the number of macrophages in normal or diabetic conditions of wistar rats

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    Rochman Mujayanto

    2017-03-01

    Full Text Available Background: Therapy for chronic ulcer in diabetic patient is by modifying local inflammation response using drugs that acts as immunomodulator, neuromodulator and growth factors stimulator. Topical zinc is one of drug that can modifiy local inflammation response, immunostimulation or immunosuppresion. Purpose: This study was to prove about the number of macrophage in oral ulcer between normal and diabetes microscopically and the difference if treated by 1% ZnSO4 gel topically. Method: Ulcer in lower labial mucosa was made in normal and diabetic Wistar rats (induced by STZ, then applied 1% ZnSO4 gel and CMC-Na gel as control. They were decapitated in third and fifth day and specimen was made by processing lower labial mucosa Result: Microscopically, the result showed the number of macrophages in oral ulcer in diabetic condition was significantly higher than normal and the application of 1% ZnSO4 increased the number of macrophages in fifth day. Conclusion: The number of macrophages was higher in diabetic than normal condition, and was proven that topical application of 1% ZnSO4 increased the number macrophages of oral ulcer diabetic and normal condition.

  3. The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats

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    Frangou Matrona

    2010-07-01

    Full Text Available Abstract Background The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF have been shown to promote liver regeneration after major hepatectomy. Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy. Methods Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21 that received normal saline, an EPO group (n = 21, that received EPO 500 IU/kg, a GM-CSF group (n = 21 that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21 which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67. Results Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p Conclusion EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

  4. Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure.

    Science.gov (United States)

    Pinto, Tomás O C Teixeira; Lataro, Renata M; Castania, Jaci A; Durand, Marina T; Silva, Carlos A A; Patel, Kaushik P; Fazan, Rubens; Salgado, Helio C

    2016-04-01

    Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective β1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive.

  5. Hybrid electro-optical stimulation of the rat sciatic nerve induces force generation in the plantarflexor muscles

    Science.gov (United States)

    Duke, Austin R.; Peterson, Erik; Mackanos, Mark A.; Atkinson, James; Tyler, Dustin; Jansen, E. Duco

    2012-12-01

    Objective. Optical methods of neural activation are becoming important tools for the study and treatment of neurological disorders. Infrared nerve stimulation (INS) is an optical technique exhibiting spatially precise activation in the native neural system. While this technique shows great promise, the risk of thermal damage may limit some applications. Combining INS with traditional electrical stimulation, a method known as hybrid electro-optical stimulation, reduces the laser power requirements and mitigates the risk of thermal damage while maintaining spatial selectivity. Here we investigate the capability of inducing force generation in the rat hind limb through hybrid stimulation of the sciatic nerve. Approach. Hybrid stimulation was achieved by combining an optically transparent nerve cuff for electrical stimulation and a diode laser coupled to an optical fiber for infrared stimulation. Force generation in the rat plantarflexor muscles was measured in response to hybrid stimulation with 1 s bursts of pulses at 15 and 20 Hz and with a burst frequency of 0.5 Hz. Main results. Forces were found to increase with successive stimulus trains, ultimately reaching a plateau by the 20th train. Hybrid evoked forces decayed at a rate similar to the rate of thermal diffusion in tissue. Preconditioning the nerve with an optical stimulus resulted in an increase in the force response to both electrical and hybrid stimulation. Histological evaluation showed no signs of thermally induced morphological changes following hybrid stimulation. Our results indicate that an increase in baseline temperature is a likely contributor to hybrid force generation. Significance. Extraneural INS of peripheral nerves at physiologically relevant repetition rates is possible using hybrid electro-optical stimulation.

  6. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    Science.gov (United States)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  7. Functional reentry and circus movement arrhythmias in the small intestine of normal and diabetic rats.

    Science.gov (United States)

    Lammers, Wim J E P; Stephen, B; Karam, S M

    2012-04-01

    In a few recent studies, the presence of arrhythmias based on reentry and circus movement of the slow wave have been shown to occur in normal and diseased stomachs. To date, however, reentry has not been demonstrated before in any other part of the gastrointestinal system. No animals had to be killed for this study. Use was made of materials obtained during the course of another study in which 11 rats were treated with streptozotocin and housed with age-matched controls. After 3 and 7 mo, segments of duodenum, jejunum, and ileum were isolated and positioned in a tissue bath. Slow wave propagation was recorded with 121 extracellular electrodes. After the experiment, the propagation of the slow waves was reconstructed. In 10 of a total of 66 intestinal segments (15%), a circus movement of the slow wave was detected. These reentries were seen in control (n = 2) as well as in 3-mo (n = 2) and 7-mo (n = 6) diabetic rats. Local conduction velocities and beat-to-beat intervals during the reentries were measured (0.42 ± 0.15 and 3.03 ± 0.67 cm/s, respectively) leading to a wavelength of 1.3 ± 0.5 cm and a circuit diameter of 4.1 ± 1.5 mm. This is the first demonstration of a reentrant arrhythmia in the small intestine of control and diabetic rats. Calculations of the size of the circuits indicate that they are small enough to fit inside the intestinal wall. Extrapolation based on measured velocities and rates indicate that reentrant arrhythmias are also possible in the distal small intestine of larger animals including humans.

  8. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    Science.gov (United States)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; hide

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  9. Effect of triiodothyronine on adiponectin expression and leptin release by white adipose tissue of normal rats.

    Science.gov (United States)

    Cabanelas, A; Cordeiro, A; Santos Almeida, N A dos; Monteiro de Paula, G S; Coelho, V M; Ortiga-Carvalho, T M; Pazos-Moura, C C

    2010-04-01

    Previous studies have shown that alterations in thyroid status may lead to changes in serum leptin and adiponectin, both in humans and rodents. The mechanisms, especially for adiponectin, are unclear. In the present study, we investigated the effect of triiodothyronine (T3) on the expression of adiponectin mRNA and the release of leptin and adiponectin by white adipose tissue (WAT) explants obtained from epididymal (visceral) or inguinal (subcutaneous) depots from normal rats. We also analyzed the effects of other known regulators of adiponectin and leptin release, such as rosiglitazone and dexamethasone. T3 acted directly at rat WAT explants in a depot-specific manner and in a unique fashion to each hormone. T3 was able to inhibit leptin release only by epididymal explants, and to reduce adiponectin mRNA expression only in inguinal explants. However, T3 was incapable of modifying adiponectin release by both explants. Additionally, rosiglitazone exhibited an inhibitory effect on adiponectin release by both WAT explants, even though adiponectin mRNA was importantly upregulated only in inguinal explants. Rosiglitazone acted as an inhibitor of leptin release by both studied fat depots, while only epididymal explants responded to the stimulatory effect of dexamethasone on leptin release. Therefore, the present model of isolated rat white adipose tissue explants highlights the fact that the regulation of hormonal production by white adipose tissue depends on the type of depot and its anatomical location. In this context, our results show for the first time a potential inhibitory effect of T3 on adiponectin mRNA expression specifically on WAT from a subcutaneous depot. Georg Thieme Verlag KG Stuttgart New York.

  10. Estrogen normalizes perinatal nicotine-induced hypertensive responses in adult female rat offspring.

    Science.gov (United States)

    Xiao, Daliao; Huang, Xiaohui; Yang, Shumei; Zhang, Lubo

    2013-06-01

    Perinatal nicotine exposure caused a sex-dependent heightened vascular response to angiotensin II (Ang II) and increased blood pressure in adult male but not in female rat offspring. The present study tested the hypothesis that estrogen normalizes perinatal nicotine-induced hypertensive response to Ang II in female offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. Ovariectomy and 17β-estradiol replacement were performed on 8-week-old female offspring. At 5 months of age, Ang II-induced blood pressure responses were not changed by nicotine treatment in the sham groups. In contrast, nicotine significantly enhanced Ang II-induced blood pressure responses as compared with saline control in the ovariectomy groups, which was associated with increased Ang II-induced vascular contractions. These heightened responses were abrogated by 17β-estradiol replacement. In addition, nicotine enhanced Ang II receptor type I, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase type 2 protein expressions, and reactive oxygen species production of aortas as compared with saline control in the ovariectomy groups. Antioxidative agents, both apocynin and tempol, inhibited Ang II-induced vascular contraction and eliminated the differences of contractions between nicotine-treated and control ovariectomy rats. These findings support a key role of estrogen in the sex difference of perinatal nicotine-induced programming of vascular dysfunction, and suggest that estrogen may counteract heightened reactive oxygen species production, leading to protection of females from development programming of hypertensive phenotype in adulthood.

  11. Microtransplantation of acetylcholine receptors from normal or denervated rat skeletal muscles to frog oocytes

    Science.gov (United States)

    Bernareggi, Annalisa; Reyes-Ruiz, Jorge Mauricio; Lorenzon, Paola; Ruzzier, Fabio; Miledi, Ricardo

    2011-01-01

    Cell membranes, carrying neurotransmitter receptors and ion channels, can be ‘microtransplanted’ into frog oocytes. This technique allows a direct functional characterization of the original membrane proteins, together with any associated molecules they may have, still embedded in their natural lipid environment. This approach has been previously demonstrated to be very useful to study neurotransmitter receptors and ion channels contained in cell membranes isolated from human brains. Here, we examined the possibility of using the microtransplantation method to study acetylcholine receptors from normal and denervated rat skeletal muscles. We found that the muscle membranes, carrying their fetal or adult acetylcholine receptor isoforms, could be efficiently microtransplanted to the oocyte membrane, making the oocytes become sensitive to acetylcholine. These results show that oocytes injected with skeletal muscle membranes efficiently incorporate functional acetylcholine receptors, thus making the microtransplantation approach a valuable tool to further investigate receptors and ion channels of human muscle diseases. PMID:21224230

  12. Comprehensive experiment-clinical biochemistry: determination of blood glucose and triglycerides in normal and diabetic rats.

    Science.gov (United States)

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a standard clinical biochemistry exercise. The students are not only exposed to techniques and equipment but are also inspired to think more about the biochemical mechanisms of diseases. When linked with lecture topics about the metabolism of carbohydrates and lipids, the students obtain a better understanding of the relevance of abnormal metabolism in relation to diseases. Such understanding provides a solid foundation for the medical students' future research and for other clinical applications.

  13. Surface proteins in normal and transformed rat liver epithelial cells in culture.

    Science.gov (United States)

    Bannikov, G. A.; Saint Vincent, L.; Montesano, R.

    1980-01-01

    The pattern of surface proteins of different types of normal and transformed rat liver cells have been studied in culture by means of lactoperoxidase-catalysed iodination procedures, followed by SDS-gel electrophoresis. The cells examined were primary cultures of epithelial liver cells, long-term cultures of epithelial liver cells, in vitro transformed epithelial liver cell lines and liver tumour-cell lines; mesenchymal cells from liver and skin were also examined. The principal surface proteins of primary cultures of epithelial cells from adult or neonatal rats had components with mol. wts of 140,000-160,000, 100,000 and 40,000-70,000. A band that had the same position as fibronectin from mesenchymal cells was also present and this band, as well as other iodinated components, were less sensitive to trypsin than fibroblastic fibronectin. A similar pattern of iodinated proteins was seen in long-term cultures of epithelial liver cells, with a great reduction in the number and intensity of the bands in the mol. wt region below 100,000. Almost all the in vitro transformed and tumour epithelial cell lines contain a protein with a mol. wt 135,000 as one of the major iodinated bands, and in contrast to the observation in transformed fibroblasts, the fibronectin was retained by most of these transformed cell lines. Images Fig. 1 Fig. 2 Fig. 3 PMID:7053205

  14. Identification and preliminary SAR studies of (+)-Geodin as a glucose uptake stimulator for rat adipocytes.

    Science.gov (United States)

    Sato, Seiichi; Okusa, Noriyuki; Ogawa, Akiyo; Ikenoue, Takao; Seki, Tetsuya; Tsuji, Takashi

    2005-09-01

    (+)-Geodin (1) was isolated from Penicillium glabrum AJ117540 with activity that stimulates glucose uptake by rat adipocytes. Unlike insulin it is active in the presence of wortmannin. Dihydrogeodin (2) and sulochrin (3) which are the precursors of (+)-geodin biosynthesis were also isolated from the same fungus. Preliminary SAR studies of 1 showed some analogues had enhanced activity. Especially, the activities of racemic geodin and dibromo analogue (7a) were comparable to that of the natural product. Geodin (1), a known fungal metabolite, was isolated from Penicillium glabrum AJ117540 as an active substance (Fig. 1). Dihydrogeodin (2) and sulochrin (3), the precursors of 1, were also isolated from the same fungal extract. In this study, preliminary mechanistic insight and SAR are reported.

  15. Effects of magnetic stimulation on oxidative stress and skeletal muscle regeneration induced by mepivacaine in rat.

    Science.gov (United States)

    Jimena, I; Tasset, I; López-Martos, R; Rubio, A J; Luque, E; Montilla, P; Peña, J; Túnez, I

    2009-01-01

    We investigated the effect of magnetic field stimulation (MS) on oxidative damage and skeletal muscle injury prompted by mepivacaine injection in the anterior tibial muscle of Wistar rats. The effects of mepivacaine and MS on oxidative stress were evaluated by lipid peroxidation, GSH levels and catalase activity. Muscle regeneration was analyzed by haematoxylin-eosin stained, NADH-TR histochemical reaction, desmin immunostaining as well as by morphometric parameters such as fibers density and fiber area were evaluated. Our data revealed that mepivacaine induced oxidative stress, that MS prevents the harmful effects induced by mepivacaine and that it facilitates the regeneration process of skeletal muscle. In conclusion, the results show the ability of MS to modify skeletal muscle response to mepivacaine.

  16. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats.

    Science.gov (United States)

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka

    2009-07-01

    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  17. Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

    Directory of Open Access Journals (Sweden)

    Zora Djuric

    2017-08-01

    Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

  18. Intrastriatal grafts of fetal ventral mesencephalon improve allodynia-like withdrawal response to mechanical stimulation in a rat model of Parkinson's disease.

    Science.gov (United States)

    Takeda, Ryuichiro; Ishida, Yasushi; Ebihara, Kosuke; Abe, Hiroshi; Matsuo, Hisae; Ikeda, Tetsuya; Koganemaru, Go; Kuramashi, Aki; Funahashi, Hideki; Magata, Yasuhiro; Kawai, Keiichi; Nishimori, Toshikazu

    2014-06-24

    We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

    Science.gov (United States)

    Sieber, C C; Sumanovski, L T; Moll-Kaufmann, C; Stalder, G A

    1997-11-01

    Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition

  20. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  1. R-MC46 monoclonal antibody stimulates adhesion and phagocytosis by rat macrophages

    Directory of Open Access Journals (Sweden)

    Gašić Sonja

    2004-01-01

    Full Text Available Background. In our previous experiments it was shown that R-MC46 monoclonal antibody (mAb, produced at our Institute, stimulated homotypic aggregation of rat granulocytes and production of proinflammatory cytokines. The aim of this study was to examine antigen expression and function, recognized by R-MC46 mAb on macrophages. Methods. The expression of R-MC46 antigen on thymic and peritoneal macrophages was investigated using immunocytochemistry and flow cytometry methods. Its biochemical characterization was performed by Western blot. The ability of R-MC46 mAb to modulate adhesion and phagocytosis by macrophages was studied by using co-culture experiments with autologous thymocytes. Results. R-MC46 mAb stained thymic macrophages more strongly than peritoneal macrophages. After in vivo treatment of peritoneal macrophages with Pristane, a significant up-regulation of the R-MC46 antigen expression was observed. Western blot analysis showed that the mAb recognized a low molecular weight antigen of about 5.5 kDa. R-MC46 mAb significantly enhanced binding and phagocytosis of thymocytes by both thymic and peritoneal macrophages. These processes were completely blocked by WT.3 (anti-CD18 mAb. The stimulation of binding thymocyte to macrophages was higher with the use of thymic macrophages,while the phagocytosis of these cells was higher in the presence of peritoneal macrophages. Conclusion. R-MC46 mAb recognized a new molecule expressed by rat macrophages. The antigen is most probably involved in β2 integrin-mediated adhesion and phagocytosis, as well as proinflammatory functions of macrophages.

  2. Therapeutic ultrasound to stimulate osteoconduction - A placebo controlled single blind study using e-PTFE membranes in rats

    NARCIS (Netherlands)

    Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B

    2004-01-01

    To decrease heating time of bone defects covered with osteoconductive membranes, an attempt was made to stimulate the osteoconductive process with therapeutic ultrasound. In 72 rats, a circular mandibular defect was created and covered on both sides with an e-PTFE membrane. A control group, an ultra

  3. The acute and chronic effect of vagus nerve stimulation in genetic absence epilepsy rats from Strasbourg (GAERS)

    NARCIS (Netherlands)

    S Dedeurwaerdere; K. Vonck; P Hese van; W.J. Wadman; P Boon

    2005-01-01

    PURPOSE: The aim of this study was to evaluate the efficacy of acute and chronic vagus nerve stimulation (VNS) in genetic absence epilepsy rats from Strasbourg (GAERS). This is a validated model for absence epilepsy, characterized by frequent spontaneous absences concomitant with spike and wave disc

  4. D-2-like receptor stimulation decreases effective renal plasma flow and glomerular filtration rate in spontaneously hypertensive rats

    NARCIS (Netherlands)

    de Vries, PAM; de Jong, PE; de Zeeuw, D; Navis, GJ

    2002-01-01

    In spontaneously hypertensive rats (SHRs) the dopaminergic D-1-like renal vasodilator response is impaired. The renal vascular response to D-2-like receptor stimulation in vivo is incompletely known. Therefore, renal hemodynamics were studied in conscious SHRs during continuous infusion of D-2-like

  5. Ultrasound to stimulate mandibular bone defect healing : A placebo-controlled single-blind study in rats

    NARCIS (Netherlands)

    Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B

    2004-01-01

    Purpose: Because of the limitations of the body to heal large maxillofacial bone defects, an attempt was made to stimulate mandibular defect healing with low intensity pulsed ultrasound in rats. This ultrasound consists of a 1.5-MHz pressure wave administered in pulses of 200 musec, with an average

  6. The thymus atrophy inducing organotin compound DBTC stimulates TCRalfabeta-CD3 signalling in immature rat thymocytes

    NARCIS (Netherlands)

    Pieters, R.H.H.; Punt, P.; Bol, M.; Dijken, J.M. van; Seinen, W.; Penninks, A.H.

    1995-01-01

    In the present study, we show that the thymus atrophy inducing compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together

  7. Ser-2030, but not Ser-2808, is the major phosphorylation site in cardiac ryanodine receptors responding to protein kinase A activation upon beta-adrenergic stimulation in normal and failing hearts.

    Science.gov (United States)

    Xiao, Bailong; Zhong, Guofeng; Obayashi, Masakazu; Yang, Dongmei; Chen, Keyun; Walsh, Michael P; Shimoni, Yakhin; Cheng, Heping; Ter Keurs, Henk; Chen, S R Wayne

    2006-05-15

    We have recently shown that RyR2 (cardiac ryanodine receptor) is phosphorylated by PKA (protein kinase A/cAMP-dependent protein kinase) at two major sites, Ser-2030 and Ser-2808. In the present study, we examined the properties and physiological relevance of phosphorylation of these two sites. Using site- and phospho-specific antibodies, we demonstrated that Ser-2030 of both recombinant and native RyR2 from a number of species was phosphorylated by PKA, indicating that Ser-2030 is a highly conserved PKA site. Furthermore, we found that the phosphorylation of Ser-2030 responded to isoproterenol (isoprenaline) stimulation in rat cardiac myocytes in a concentration- and time-dependent manner, whereas Ser-2808 was already substantially phosphorylated before beta-adrenergic stimulation, and the extent of the increase in Ser-2808 phosphorylation after beta-adrenergic stimulation was much less than that for Ser-2030. Interestingly, the isoproterenol-induced phosphorylation of Ser-2030, but not of Ser-2808, was markedly inhibited by PKI, a specific inhibitor of PKA. The basal phosphorylation of Ser-2808 was also insensitive to PKA inhibition. Moreover, Ser-2808, but not Ser-2030, was stoichiometrically phosphorylated by PKG (protein kinase G). In addition, we found no significant phosphorylation of RyR2 at the Ser-2030 PKA site in failing rat hearts. Importantly, isoproterenol stimulation markedly increased the phosphorylation of Ser-2030, but not of Ser-2808, in failing rat hearts. Taken together, these observations indicate that Ser-2030, but not Ser-2808, is the major PKA phosphorylation site in RyR2 responding to PKA activation upon beta-adrenergic stimulation in both normal and failing hearts, and that RyR2 is not hyperphosphorylated by PKA in heart failure. Our results also suggest that phosphorylation of RyR2 at Ser-2030 may be an important event associated with altered Ca2+ handling and cardiac arrhythmia that is commonly observed in heart failure upon beta

  8. Ser-2030, but not Ser-2808, is the major phosphorylation site in cardiac ryanodine receptors responding to protein kinase A activation upon β-adrenergic stimulation in normal and failing hearts

    Science.gov (United States)

    Xiao, Bailong; Zhong, Guofeng; Obayashi, Masakazu; Yang, Dongmei; Chen, Keyun; Walsh, Michael P.; Shimoni, Yakhin; Cheng, Heping; ter Keurs, Henk; Chen, S. R. Wayne

    2006-01-01

    We have recently shown that RyR2 (cardiac ryanodine receptor) is phosphorylated by PKA (protein kinase A/cAMP-dependent protein kinase) at two major sites, Ser-2030 and Ser-2808. In the present study, we examined the properties and physiological relevance of phosphorylation of these two sites. Using site- and phospho-specific antibodies, we demonstrated that Ser-2030 of both recombinant and native RyR2 from a number of species was phosphorylated by PKA, indicating that Ser-2030 is a highly conserved PKA site. Furthermore, we found that the phosphorylation of Ser-2030 responded to isoproterenol (isoprenaline) stimulation in rat cardiac myocytes in a concentration- and time-dependent manner, whereas Ser-2808 was already substantially phosphorylated before β-adrenergic stimulation, and the extent of the increase in Ser-2808 phosphorylation after β-adrenergic stimulation was much less than that for Ser-2030. Interestingly, the isoproterenol-induced phosphorylation of Ser-2030, but not of Ser-2808, was markedly inhibited by PKI, a specific inhibitor of PKA. The basal phosphorylation of Ser-2808 was also insensitive to PKA inhibition. Moreover, Ser-2808, but not Ser-2030, was stoichiometrically phosphorylated by PKG (protein kinase G). In addition, we found no significant phosphorylation of RyR2 at the Ser-2030 PKA site in failing rat hearts. Importantly, isoproterenol stimulation markedly increased the phosphorylation of Ser-2030, but not of Ser-2808, in failing rat hearts. Taken together, these observations indicate that Ser-2030, but not Ser-2808, is the major PKA phosphorylation site in RyR2 responding to PKA activation upon β-adrenergic stimulation in both normal and failing hearts, and that RyR2 is not hyperphosphorylated by PKA in heart failure. Our results also suggest that phosphorylation of RyR2 at Ser-2030 may be an important event associated with altered Ca2+ handling and cardiac arrhythmia that is commonly observed in heart failure upon

  9. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    Science.gov (United States)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  10. The effects of electrical and optical stimulation of midbrain dopaminergic neurons on rat 50-kHz ultrasonic vocalizations

    Directory of Open Access Journals (Sweden)

    Tina eScardochio

    2015-12-01

    Full Text Available AbstractRationale Adult rats emit ultrasonic vocalizations (USVs at around 50-kHz ; these commonly occur in contexts that putatively engender positive affect. While several reports indicate that dopaminergic (DAergic transmission plays a role in the emission of 50-kHz calls, the pharmacological evidence is mixed. Different modes of dopamine (DA release (i.e. tonic and phasic could potentially explain this discrepancy.Objective To investigate the potential role of phasic DA release in 50-kHz call emission.Methods In Experiment 1, USVs were recorded in adult male rats following unexpected electrical stimulation of the medial forebrain bundle (MFB. In parallel, phasic DA release in the nucleus accumbens (NAcc was recorded using fast-scan cyclic voltammetry. In Experiment 2, USVs were recorded following response-contingent or non-contingent optogenetic stimulation of midbrain DAergic neurons. Four 20-s schedules of optogenetic stimulation were used: fixed-interval, fixed-time, variable-interval and variable-time.Results Brief electrical stimulation of the MFB increased both 50-kHz call rate and phasic DA release in the NAcc. During optogenetic stimulation sessions, rats initially called at a high rate comparable to that observed following reinforcers such as psychostimulants. Although optogenetic stimulation maintained reinforced responding throughout the 2-hour session, the call rate declined to near zero within the first 30 minutes. The trill call subtype predominated following both electrical and optical stimulation.Conclusion The occurrence of electrically-evoked 50-kHz calls, time-locked to phasic DA (Experiment 1, provides correlational evidence supporting a role for phasic DA in USV production. However, in Experiment 2, the temporal dissociation between calling and optogenetic stimulation of midbrain DAergic neurons suggests that phasic mesolimbic DA release is not sufficient to produce 50-kHz calls. The emission of the trill subtype of 50-k

  11. Stimulating effects of quercetin on sperm quality and reproductive organs in adult male rats

    Institute of Scientific and Technical Information of China (English)

    Ladachart Taepongsorat; Prakong Tangpraprutgul; Noppadon Kitana; Suchinda Malaivijitnond

    2008-01-01

    Aim: To investigate effects of quercetin on weight and histology of testis and accessory sex organs and on sperm quality in adult male rats. Methods: Male Sprague-Dawley rats were injected s.c. with quercetin at the dose of 0, 30,90, or 270 mg/kg body weight/day (hereafter abbreviated Q0, Q30, Q90 and Q270, respectively), and each dose was administered for treatment durations of 3, 7 and 14 days. Results: From our study, it was found that the effects of quercetin on reproductive organs and sperm quality depended on the dose and duration of treatment. After Q270 treatment for 14 days, the weights of testes, epididymis and vas deferens were significantly increased, whereas the weights of seminal vesicle and prostate gland were significantly decreased, compared with those of Q0. The histo-logical alteration of those organs was observed after Q270 treatment for 7 days as well as 14 days. The sperm motility, viability and concentration were significantly increased after Q90 and Q270 injections after both of 7 and 14 days. Changes in sperm quality were earlier and greater than those in sex organ histology and weight, respectively.Conclusion: Overall results indicate that quercetin might indirectly affect sperm quality through the stimulation of the sex organs, both at the cellular and organ levels, depending on the dose and the duration of treatment. Therefore, the use of quercetin as an alternative drug for treatment of male infertility should be considered.

  12. Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex.

    Science.gov (United States)

    Sgaravatti, Angela M; Magnusson, Alessandra S; de Oliveira, Amanda S; Rosa, Andréa P; Mescka, Caroline Paula; Zanin, Fernanda R; Pederzolli, Carolina D; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir; Dutra-Filho, Carlos Severo

    2009-09-01

    Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism especially in tyrosinemia type II which is caused by deficiency of tyrosine aminotransferase (TAT) and provokes eyes, skin and central nervous system disturbances. We have recently reported that tyrosine promoted oxidative stress in vitro but the exact mechanisms of brain damage in these disorder are poorly known. In the present study, we investigated the in vivo effect of L-tyrosine (500 mg/Kg) on oxidative stress indices in cerebral cortex homogenates of 14-day-old Wistar rats. A single injection of L-tyrosine decreased glutathione (GSH) and thiol-disulfide redox state (SH/SS ratio) while thiobarbituric acid-reactive substances, protein carbonyl content and glucose-6-phosphate dehydrogenase activity were enhanced. In contrast, the treatment did not affect ascorbic acid content, and the activities of superoxide dismutase, catalase and glutathione peroxidase. These results indicate that acute administration of L-tyrosine may impair antioxidant defenses and stimulate oxidative damage to lipids and proteins in cerebral cortex of young rats in vivo. This suggests that oxidative stress may represent a pathophysiological mechanism in hypetyrosinemic patients.

  13. High-frequency transcutaneous electrical nerve stimulation alters thermal but not mechanical allodynia following chronic constriction injury of the rat sciatic nerve.

    Science.gov (United States)

    Somers, D L; Clemente, F R

    1998-11-01

    To determine if daily transcutaneous electrical nerve stimulation (TENS) can alter the thermal and mechanical allodynia that develops after chronic constriction injury (CCI) to the right sciatic nerve of rats. A completely randomized experimental design was used. Four groups of rats underwent CCI surgery to the right sciatic nerve and either were not treated with TENS or received TENS starting at different times after the CCI surgery. TENS was delivered daily for 1 hour to CCI rats through self-adhesive electrodes applied to skin innervated by the right dorsal rami of lumbar spinal nerves L1-6. Rats of different groups received daily TENS starting immediately, 20 to 30 hours, or 3 days after the CCI surgery. Thermal and mechanical pain thresholds of hind paws were assessed bilaterally in all rats twice before the CCI surgery (baseline) and then 2, 7, 12, and 14 days after surgery. Thermal and mechanical allodynia were expressed as difference scores between the pain thresholds of right and left hind paws. These values were normalized to differences that existed between the two paws at baseline. Daily TENS beginning immediately after CCI surgery prevented the development of thermal allodynia at all assessment times (p < .05). Daily TENS starting 1 day after surgery reduced thermal allodynia, but only on days 2 and 14 (p < .05). Daily TENS beginning 3 days after surgery had no effect on the development of thermal allodynia. Regardless of when it was started, daily TENS did not consistently alter mechanical allodynia in CCI rats. It appears that daily TENS can prevent thermal but not mechanical allodynia in this model. However, early intervention with the treatment is critical if it is to be effective at all.

  14. δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice.

    Science.gov (United States)

    Kaneko, Kentaro; Mizushige, Takafumi; Miyazaki, Yuri; Lazarus, Michael; Urade, Yoshihiro; Yoshikawa, Masaaki; Kanamoto, Ryuhei; Ohinata, Kousaku

    2014-02-15

    The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat diet intake as well. [D-Pen(2,5)]-enkephalin (DPDPE), an agonist selective for the δ-receptor, increased normal diet intake after central administration to nonfasted male mice. The orexigenic activity of DPDPE was inhibited by blockade of cyclooxygenase (COX)-2, lipocalin-type prostaglandin D synthase (L-PGDS), D-type prostanoid receptor 1 (DP(1)), and neuropeptide Y (NPY) receptor type 1 (Y1) for PGD(2) and NPY, respectively, suggesting that this was mediated by the PGD(2)-NPY system. In contrast, DPDPE decreased high-fat diet intake in mice fed a high-fat diet. DPDPE-induced suppression of high-fat diet intake was blocked by antagonists of melanocortin 4 (MC(4)) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. These results suggest that central δ-opioid receptor activation suppresses high-fat diet intake via the MC-CRF system, independent of the orexigenic PGD(2) system. Furthermore, orally administered rubiscolin-6, an opioid peptide derived from spinach Rubisco, suppressed high-fat diet intake. This suppression was also blocked by centrally administered naltrindole, an antagonist for the δ-receptor, suggesting that rubiscolin-6 suppressed high-fat diet intake via activation of central δ-opioid receptor.

  15. Consecutive 15 min is necessary for focal low frequency stimulation to inhibit amygdaloid-kindling seizures in rats.

    Science.gov (United States)

    Liu, Yang; Wang, Yi; Xu, Zhenghao; Xu, Cenglin; Ying, Xiaoying; Wang, Shuang; Zhang, Shihong; Xiao, Bo; Chen, Zhong

    2013-09-01

    Low-frequency stimulation (LFS) is emerging as a new option for the treatment of intractable epilepsy. The stimulation duration may influence the anti-epileptic effect of LFS but is poorly studied. The present study was designed to evaluate the anti-epileptic effect of focal LFS with different stimulation duration on amygdaloid-kindling seizures in rats. We found 15 and 30 min but not 1 or 5 min LFS delivered immediately after the kindling stimulation slowed the progression of behavioral seizure stages and reduced mean afterdischarge duration (ADD) during kindling acquisition. In fully kindled animals, 15 and 30min rather than 1 and 5 min LFS decreased the incidence of generalized seizures and the average seizure stage as well as shortened the cumulative generalized seizure duration (GSD). Meanwhile, EEG analysis showed 15 and 30 min LFS specifically lowered the power in delta band. However, if 15min LFS delivered intermittently by 5 min interval, it had no suppressing effect on kindling rat. Thus, it is likely that consecutive 15 min is necessary for LFS to inhibit amygdaloid-kindling seizures in rats, indicating the stimulation duration may be a key fact affecting the clinical effect of LFS on epilepsy.

  16. Tranexamic acid induces kaolin intake stimulating a pathway involving tachykinin neurokinin 1 receptors in rats.

    Science.gov (United States)

    Kakiuchi, Hitoshi; Kawarai-Shimamura, Asako; Kuwagata, Makiko; Orito, Kensuke

    2014-01-15

    Tranexamic acid suppresses post-partum haemorrhage and idiopathic menorrhagia through its anti-fibrinolytic action. Although it is clinically useful, it is associated with high risks of side effects such as emesis. Understanding the mechanisms underlying tranexamic acid-induced emesis is very important to explore appropriate anti-emetic drugs for the prevention and/or suppression of emesis. In this study, we examined the receptors involved in tranexamic acid-induced kaolin intake in rats, which reflects the drug's clinical emetogenic potential in humans. Further, we examined the brain regions activated by administration of tranexamic acid and elucidated pivotal pathways of tranexamic acid-induced kaolin intake. We examined the effects of ondansetron, a 5-hydroxytryptamine 3 receptor antagonist, domperidone, a dopamine 2 receptor antagonist, and aprepitant, a tachykinin neurokinin 1 (NK1) receptor antagonist, on tranexamic acid-induced kaolin intake in rats. Then, we determined the brain regions that showed increased numbers of c-Fos immunoreactive cells. Finally, we examined the effects of an antagonist(s) that reduced tranexamic acid-induced kaolin intake on the increase in c-Fos immunoreactive cells. Aprepitant significantly decreased tranexamic acid-induced kaolin intake. However, neither ondansetron nor domperidone decreased kaolin intake. Tranexamic acid significantly increased c-Fos immunoreactive cells by approximately 5.5-fold and 22-fold in the area postrema and nucleus of solitary tract, respectively. Aprepitant decreased the number of c-Fos immunoreactive cells in both areas. Tranexamic acid induced kaolin intake possibly via stimulation of tachykinin NK1 receptors in rats. The tachykinin NK1 receptor could be targeted to prevent and/or suppress emesis in patients receiving tranexamic acid. © 2013 Published by Elsevier B.V.

  17. Levodopa enhances immobility induced by spinal cord electromagnetic stimulation in rats.

    Science.gov (United States)

    Sales, Paulo M G; de Andrade, Loraine M S; Pitcher, Meagan R; Rola, Francisco H; Gondim, Francisco de A A

    2016-10-28

    The repetitive ElectroMagnetic Stimulation (rEMS) is an innocuous method applied to modulate neurocircuits in real-time to study the physiology of the central nervous system and treat neuropsychiatric conditions. Preliminary data suggest that spinal rEMS induces behavioral changes in awake rats. However, the mechanisms behind this phenomenon remain largely unknown. Twenty-five male Wistar rats were divided into five subgroups of five animals each: one subgroup was drug-free, two subgroups received Levodopa+Benserazide 250+25mg/kg for two or seven days, and the remaining two subgroups received Haloperidol 0.1 or 0.3mg/kg for two days. The animals were restrained during sham rEMS (day 1) followed by real rEMS of the cervicothoracic region at a different day (day 2 or 7, depending on subgroup). Four behavioral parameters were quantified: Walking, Climbing, Grooming, and Cornering. rEMS reduced Walking and increased Cornering duration when applied over the cervicothoracic region of drug-free animals. A pretreatment with Levodopa+Benserazide for two or seven days induced an additional decrease in Walking after rEMS. This reduction was maximum after the treatment for seven days and associated with extinction of Climbing and increase in Cornering. A pretreatment with Haloperidol 0.1mg/kg reduced Grooming after rEMS, but did not prevent the reduction in Walking. Cervicothoracic rEMS induced complex immobility responses that are in part modulated by dopaminergic pathways in rats. Further studies are necessary to determine the specific mechanisms involved. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Can transcutaneous electrical nerve stimulation improve achilles tendon healing in rats?

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    Roberta A. C. Folha

    2015-12-01

    Full Text Available BACKGROUND: Tendon injury is one of the most frequent injuries in sports activities. TENS is a physical agent used in the treatment of pain but its influence on the tendon's healing process is unclear. OBJECTIVE: To evaluate the influence of TENS on the healing of partial rupture of the Achilles tendon in rats. METHOD: Sixty Wistar rats were submitted to a partial rupture of the Achilles tendon by direct trauma and randomized into six groups (TENS or Sham stimulation and the time of evaluation (7, 14, and 21 days post-injury. Burst TENS was applied for 30 minutes, 6 days, 100 Hz frequency, 2 Hz burst frequency, 200 µs pulse duration, and 300 ms pulse train duration. Microscopic analyses were performed to quantify the blood vessels and mast cells, birefringence to quantify collagen fiber alignment, and immunohistochemistry to quantify types I and III collagen fibers. RESULTS: A significant interaction was observed for collagen type I (p=0.020 where the TENS group presented lower percentage in 14 days after the lesion (p=0.33. The main group effect showed that the TENS group presented worse collagen fiber alignment (p=0.001 and lower percentage of collagen III (p=0.001 and the main time effect (p=0.001 showed decreased percentage of collagen III at 7 days (p=0.001 and 14 days (p=0.001 after lesion when compared to 21 days. CONCLUSIONS: Burst TENS inhibited collagen I and III production and impaired its alignment during healing of partial rupture of the Achilles tendon in rats.

  19. Can transcutaneous electrical nerve stimulation improve achilles tendon healing in rats?

    Science.gov (United States)

    Folha, Roberta A. C.; Pinfildi, Carlos E.; Liebano, Richard E.; Rampazo, Érika P.; Pereira, Raphael N.; Ferreira, Lydia M.

    2015-01-01

    BACKGROUND: Tendon injury is one of the most frequent injuries in sports activities. TENS is a physical agent used in the treatment of pain but its influence on the tendon's healing process is unclear. OBJECTIVE: To evaluate the influence of TENS on the healing of partial rupture of the Achilles tendon in rats. METHOD: Sixty Wistar rats were submitted to a partial rupture of the Achilles tendon by direct trauma and randomized into six groups (TENS or Sham stimulation) and the time of evaluation (7, 14, and 21 days post-injury). Burst TENS was applied for 30 minutes, 6 days, 100 Hz frequency, 2 Hz burst frequency, 200 µs pulse duration, and 300 ms pulse train duration. Microscopic analyses were performed to quantify the blood vessels and mast cells, birefringence to quantify collagen fiber alignment, and immunohistochemistry to quantify types I and III collagen fibers. RESULTS: A significant interaction was observed for collagen type I (p=0.020) where the TENS group presented lower percentage in 14 days after the lesion (p=0.33). The main group effect showed that the TENS group presented worse collagen fiber alignment (p=0.001) and lower percentage of collagen III (p=0.001) and the main time effect (p=0.001) showed decreased percentage of collagen III at 7 days (p=0.001) and 14 days (p=0.001) after lesion when compared to 21 days. CONCLUSIONS: Burst TENS inhibited collagen I and III production and impaired its alignment during healing of partial rupture of the Achilles tendon in rats. PMID:26647744

  20. Effect of Electroacupuncture on Rat Ischemic Brain Injury: Importance of Stimulation Duration

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    Fei Zhou

    2013-01-01

    Full Text Available We explored the optimal duration of electroacupuncture (EA stimulation for protecting the brain against ischemic injury. The experiments were carried out in rats exposed to right middle cerebral artery occlusion (MCAO for 60 min followed by 24-hr reperfusion. EA was delivered to “Shuigou” (Du 26 and “Baihui” (Du 20 acupoints with sparse-dense wave (5/20 Hz at 1.0 mA for 5, 15, 30, and 45 min, respectively. The results showed that 30 min EA, starting at 5 minutes after the onset of MCAO (EA during MCAO or 5 minutes after reperfusion (EA after MCAO, significantly reduced ischemic infarct volume, attenuated neurological deficits, and decreased death rate with a larger reduction of the ischemic infarction in the former group. Also in the group of EA during MCAO, this protective benefit was positively proportional to the increase in the period of stimulation, that is, increased protection in response to EA from 5- to 30-min stimulation. In all groups, EA induced a significant increase in cerebral blood flow and promoted blood flow recovery after reperfusion, and both blood flow volume and blood cell velocity returned to the preischemia level in a short period of time. Surprisingly, EA for 45 min did not show reduction in the neurological deficits or the infarct volume and instead demonstrated an increase in death rate in this group. Although EA for 45 min still increased the blood flow during MCAO, it led to a worsening of perfusion after reperfusion compared to the group subjected only to ischemia. The neuroprotection induced by an “optimal” period (30 min of EA was completely blocked by Naltrindole, a δ-opioid receptor (DOR antagonist (10 mg/kg, i.v.. These findings suggest that earlier EA stimulation leads to better outcomes, and that EA-induced neuroprotection against ischemia depends on an optimal EA-duration via multiple pathways including DOR signaling, while “over-length” stimulation exacerbates the ischemic

  1. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    Science.gov (United States)

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17β-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  2. Effect of Intermittent Low-Frequency Electrical Stimulation on the Rat Gastrocnemius Muscle

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    Arata Tsutaki

    2013-01-01

    Full Text Available Low-frequency neuromuscular electrical stimulation (NMES has been used as an endurance exercise model. This study aimed to test whether low-frequency NMES increases the phosphorylation of anabolic signaling molecules and induces skeletal muscle hypertrophy, as seen with high-frequency NMES. Using Sprague-Dawley rats, 1 bout of exercise (with dissection done immediately (Post0 and 3 h (Post3 after exercise and another 6 sessions of training were performed. All experimental groups consisted of high- and low-frequency stimulation (HFS: 100 Hz; LFS: 10 Hz. Periodic acid-Schiff (PAS staining was conducted to investigate type II fiber activation, and western blot analysis (WB was conducted to examine whether NMES leads to anabolic intracellular signaling. At first, we examined the acute effect of exercise. PAS staining revealed that glycogen depletion occurred in both type I and type II fibers. WB results demonstrated that p70S6K phosphorylation was significantly increased by HFS, but there was no significant difference with LFS. In contrast, ERK 1/2 phosphorylation was increased by LFS at Post0. In the 6-session training, the wet weight and myofibrillar protein were significantly increased by both HFS and LFS. In conclusion, LFS has a similar anabolic effect for skeletal muscle hypertrophy as HFS, but the mediating signaling pathway might differ.

  3. Leucaena leucocephala fruit aqueous extract stimulates adipogenesis, lipolysis, and glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Kuppusamy, Umah Rani; Arumugam, Bavani; Azaman, Nooriza; Jen Wai, Chai

    2014-01-01

    Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro "insulin-like" activities of Leucaena leucocephala (Lam.) deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1) involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  4. Leucaena leucocephala Fruit Aqueous Extract Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in Primary Rat Adipocytes

    Directory of Open Access Journals (Sweden)

    Umah Rani Kuppusamy

    2014-01-01

    Full Text Available Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro “insulin-like” activities of Leucaena leucocephala (Lam. deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1 involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  5. Lesions of rat skeletal muscle after local block of acetylcholinesterase and neuromuscular stimulation.

    Science.gov (United States)

    Mense, S; Simons, D G; Hoheisel, U; Quenzer, B

    2003-06-01

    In skeletal muscle, a local increase of acetylcholine (ACh) in a few end plates has been hypothesized to cause the formation of contraction knots that can be found in myofascial trigger points. To test this hypothesis in rats, small amounts of an acetylcholinesterase inhibitor [diisopropylfluorophosphate (DFP)] were injected into the proximal half of the gastrocnemius muscle, and the muscle nerve was electrically stimulated for 30-60 min for induction of muscle twitches. The distal half of the muscle, which performed the same contractions, served as a control to assess the effects of the twitches without DFP. Sections of the muscle were evaluated for morphological changes in relation to the location of blocked end plates. Compared with the distal half of the muscle, the DFP-injected proximal half exhibited significantly higher numbers of abnormally contracted fibers (local contractures), torn fibers, and longitudinal stripes. DFP-injected animals in which the muscle nerve was not stimulated and that were allowed to survive for 24 h exhibited the same lesions but in smaller numbers. The data indicate that an increased concentration of ACh in a few end plates causes damage to muscle fibers. The results support the assumption that a dysfunctional end plate exhibiting increased release of ACh may be the starting point for regional abnormal contractions, which are thought to be essential for the formation of myofascial trigger points.

  6. Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

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    Akira Marine

    2014-01-01

    Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

  7. Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.

    Science.gov (United States)

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Yang, Qing; Wang, Yajie; Guo, Yan; Zhou, Bingbing; Weng, Xiaogang; Liu, Xuchen; Li, Yujie; Zhu, Xiaoxin; Dong, Yu

    2015-10-01

    Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.

  8. Vasopressin content in the cerebrospinal fluid and fluid perfusing cerebral ventricles in rats after the afferent vagus nerve fibres stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    Experiments were carried out on male rats in urethane anaesthesia. Cerebroventricular system was perfused with McIlwain-Rodniht`s solution from lateral ventricles to cerebellomedullary cistern. Both vagus nerves were cut and the central ends of the nerves were electrically stimulated during the collection of the third 30-min portion of perfusing fluid. Vasopressin (AVP) was determined by radioimmunoassay in samples of the cerebrospinal fluid (CSF) (the first portion) and in five successive samples of the perfusing fluid. AVP concentration in the CSF was several times greater than in the fluid perfusing cerebral ventricles. Alternate electrical stimulation of both vagus nerves did not change considerably the release of AVP into the fluid perfusing the cerebral ventricles in rat, although a certain upward tendency could be observed. It seems that only AVP raised in circulating blood and not in CSF, after vagus nerves stimulation may act on the central nervous structures. (author). 37 refs, 3 figs, 1 tab.

  9. Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats.

    Science.gov (United States)

    Xiao, Zhao; Juan, Long; Song, Yun; Zhijian, Zhang; Jing, Jin; Kun, Yu; Yuna, Hao; Dongfa, Dai; Lili, Ding; Liuxin, Tan; Fei, Liang; Nan, Liu; Fang, Yuan; Yuying, Sun; Yongzhi, Xi

    2015-01-01

    A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4(+)CD29(+)T cells to systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3 mg/kg, vaccination of normal rats with 300 μg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P > 0.05). However, transforming growth factor (TGF)-β levels were significantly increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P 0.05), with the exception of Treg cells, which were significantly

  10. Receptors involved in moxonidine-stimulated atrial natriuretic peptide release from isolated normotensive rat hearts.

    Science.gov (United States)

    Mukaddam-Daher, Suhayla; Menaouar, Ahmed; Gutkowska, Jolanta

    2006-07-10

    Imidazoline I1-receptors are present in the heart and may be involved in atrial natriuretic peptide (ANP) release. The following studies investigated whether moxonidine (an antihypertensive imidazoline I1-receptor and alpha2-adrenoceptor agonist) acts directly on the heart to stimulate ANP release, and to characterize the receptor type involved in this action. Perfusion of rat (200-225 g) isolated hearts with moxonidine (10(-6) and 10(-5) M), for 30 min, resulted in ANP release (83+/-29 and 277+/-70 ng/30 min, above basal, respectively), significantly (Palpha1-adrenoceptors), and prazosin (alpha1>alpha2-adrenoceptors), but increased by rauwolscine (alpha2-adrenoceptors). Perfusion with 10(-5) M brimonidine (full alpha2-adrenoceptor agonist) inhibited moxonidine-stimulated ANP release. Similarly, moxonidine (10(-6) M) tended to reduce coronary flow, but significantly increased coronary flow in the presence of brimonidine, which was vasoconstrictive when perfused alone. Coronary flow was reduced by 10(-5) M each, brimonidine>clonidine>moxonidine; while similar bradycardia was observed with clonidine and moxonidine, but not with brimonidine. In conclusion, these results argue in favor of moxonidine acting primarily on imidazoline I1-receptors to release ANP, with both alpha2-adrenoceptor and imidazoline I1-receptors exerting inhibitory inter-relation. In contrast, the coronary vasodilatory effect of moxonidine requires full activation of alpha2-adrenoceptor. The sympatholytic and ANP-releasing effects of moxonidine appear to be mediated by cardiac imidazoline receptors that may be differentially localized. Most importantly, moxonidine can stimulate ANP release from the heart without contribution of the central nervous system.

  11. Suppression of axonal conduction by sinusoidal stimulation in rat hippocampus in vitro

    Science.gov (United States)

    Jensen, A. L.; Durand, D. M.

    2007-06-01

    Deep brain stimulation (DBS), also known as high frequency stimulation (HFS), is a well-established therapy for Parkinson's disease and essential tremor, and shows promise for the therapeutic control of epilepsy. However, the direct effect of DBS on neural elements close to the stimulating electrode remains an important unanswered question. Computational studies have suggested that HFS has a dual effect on neural elements inhibiting cell bodies, while exciting axons. Prior experiments have shown that sinusoidal HFS (50 Hz) can suppress synaptic and non-synaptic cellular activity in several in vitro epilepsy models, in all layers of the hippocampus. However, the effects of HFS on axons near the electrode are still unclear. In the present study, we tested the hypothesis that HFS suppresses axonal conduction in vitro. Sinusoidal HFS was applied to the alvear axon field of transverse rat hippocampal slices. The results show that HFS suppresses the alvear compound action potential (CAP) as well as the CA1 antidromic evoked potential (AEP). Complete suppression was observed as a 100% reduction in the amplitude of the evoked field potential for the duration of the stimulus. Evoked potential width and latency were not significantly affected by sinusoidal HFS. Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic transmission. The frequency dependence of sinusoidal HFS is similar to that observed in clinical DBS, with maximal suppression between 50 and 200 Hz. HFS produced not only suppression of axonal conduction but also a correlated rise in extracellular potassium. These data provide new insights into the effects of HFS on neuronal elements, and show that HFS can block axonal activity through non-synaptic mechanisms.

  12. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    Science.gov (United States)

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  13. Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model.

    Science.gov (United States)

    Yamakawa, Kazuma; Matsumoto, Naoya; Imamura, Yukio; Muroya, Takashi; Yamada, Tomoki; Nakagawa, Junichiro; Shimazaki, Junya; Ogura, Hiroshi; Kuwagata, Yasuyuki; Shimazu, Takeshi

    2013-01-01

    This study was performed to gain insights into novel therapeutic approaches for the treatment of heatstroke. The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation (VNS) reportedly suppresses pro-inflammatory cytokine release in several models of inflammatory disease. Here, we evaluated whether electrical VNS attenuates severe heatstroke, which induces a systemic inflammatory response. Anesthetized rats were subjected to heat stress (41.5°C for 30 minutes) with/without electrical VNS. In the VNS-treated group, the cervical vagus nerve was stimulated with constant voltage (10 V, 2 ms, 5 Hz) for 20 minutes immediately after completion of heat stress. Sham-operated animals underwent the same procedure without stimulation under a normothermic condition. Seven-day mortality improved significantly in the VNS-treated group versus control group. Electrical VNS significantly suppressed induction of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in the serum 6 hours after heat stress. Simultaneously, the increase of soluble thrombomodulin and E-selectin following heat stress was also suppressed by VNS treatment, suggesting its protective effect on endothelium. Immunohistochemical analysis using tissue preparations obtained 6 hours after heat stress revealed that VNS treatment attenuated infiltration of inflammatory (CD11b-positive) cells in lung and spleen. Interestingly, most cells with increased CD11b positivity in response to heat stress did not express α7 nicotinic acetylcholine receptor in the spleen. These data indicate that electrical VNS modulated cholinergic anti-inflammatory pathway abnormalities induced by heat stress, and this protective effect was associated with improved mortality. These findings may provide a novel therapeutic strategy to combat severe heatstroke in the critical care

  14. Oral insulin stimulates intestinal epithelial cell turnover following massive small bowel resection in a rat and a cell culture model.

    Science.gov (United States)

    Ben Lulu, Shani; Coran, Arnold G; Shehadeh, Naim; Shamir, Raanan; Mogilner, Jorge G; Sukhotnik, Igor

    2012-02-01

    We have recently reported that oral insulin (OI) stimulates intestinal adaptation after bowel resection and that OI enhances enterocyte turnover in correlation with insulin receptor expression along the villus-crypt axis. The purpose of the present study was to evaluate the effect of OI on intestinal epithelial cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS) and in a cell culture model. Caco-2 cells were incubated with increasing concentrations of insulin. Cell proliferation and apoptosis were determined by FACS cytometry. Cell viability was investigated using the Alamar Blue technique. Male rats were divided into three groups: Sham rats underwent bowel transection, SBS rats underwent a 75% bowel resection, and SBS-OI rats underwent bowel resection and were treated with OI given in drinking water (1 U/ml) from the third postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real time PCR was used to determine the level of bax and bcl-2 mRNA and western blotting was used to determine bax, bcl-2, p-ERK and AKT protein levels. Statistical analysis was performed using the one-way ANOVA test, with P statistically significant. Treatment of Caco-2 cells with insulin resulted in a significant increase in cell proliferation (twofold increase after 24 h and 37% increase after 48 h) and cell viability (in a dose-dependent manner), but did not change cell apoptosis. In a rat model of SBS, treatment with OI resulted in a significant increase in all parameters of intestinal adaptation. Elevated cell proliferation rate in insulin treated rats was accompanied by elevated AKT and p-ERK protein levels. Decreased cell apoptosis in SBS-INS rats corresponded with a decreased bax/bcl-2 ratio. Oral insulin stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat model of SBS and a cell culture model.

  15. Granulocyte colony-stimulating factor (G-CSF protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.

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    Ryo Kadota

    Full Text Available BACKGROUND: Granulocyte colony-stimulating factor (G-CSF is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. METHODS: Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne. Recombinant human G-CSF (15.0 µg/kg was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. RESULTS: Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. CONCLUSIONS: G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

  16. Expression of rat Multidrug Resistance Protein 2 (Mrp2) in male and female rats during normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny.

    Science.gov (United States)

    Johnson, David R; Guo, Grace L; Klaassen, Curtis D

    2002-09-16

    The normal maturation of biliary organic anion excretion in newborn rats can be enhanced by microsomal enzyme-inducing chemical treatment, yet the mechanism for this phenomenon is not known. Multidrug Resistance Protein 2 (Mrp2) is a biliary efflux transporter that is inducible by select microsomal enzyme-inducing chemicals. Thus, the aims of this study were to compare the normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny of Mrp2 in male and female rats. Mrp2 protein increased in an age-dependent manner in both sexes between 0 and 90 days of age. At birth, Mrp2 protein in both male and female rats was the same, approximately 70% of adult levels. Mrp2 protein in both sexes reached maximal expression levels that were higher than adult levels (male: days 25-40; female: day 45), then decreased to adult levels, at which age Mrp2 protein expression in male and female rats was the same. Second, male and female rats of various ages were treated with PCN (75 mg/kg, ip) or corn oil for 4 days, after which livers were removed and analyzed for Mrp2 protein and mRNA expression. PCN accelerated the expression of Mrp2 protein in male and female rats as early as 10 days of age, whereas, PCN did not affect male and female Mrp2 mRNA ontogeny. These data suggest that PCN increased Mrp2 protein by a sex-independent posttranscriptional mechanism.

  17. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

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    Greisen, Mia H; Altar, C Anthony; Bolwig, Tom G; Whitehead, Richard; Wörtwein, Gitta

    2005-03-15

    Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.

  18. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

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    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J. [Institute of Microcirculation, Hebei North University, Zhangjiakou, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

    2014-02-17

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na{sup +}-K{sup +}-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na{sup +}-K{sup +}-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na{sup +}-K{sup +}-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  19. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    Directory of Open Access Journals (Sweden)

    Z.G. Zhao

    2014-02-01

    Full Text Available The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL on lipopolysaccharide (LPS-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1, myeloperoxidase (MPO, and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  20. Intravitreal injection of IGFBP-3 restores normal insulin signaling in diabetic rat retina.

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    Youde Jiang

    Full Text Available Diabetes-induced changes in growth factor binding protein 3 (IGFBP-3 and tumor necrosis factor alpha (TNFα have been linked to decreased insulin receptor signaling in diabetic retinopathy. Our previous studies in retinas of diabetic rats have shown that Compound 49b, a novel β-adrenergic receptor agonist, prevented diabetic changes by increasing IGFBP-3 and decreasing TNFα, thus restoring insulin signaling and protection against diabetic retinopathy. The current study was designed to determine whether boosted expression of IGFBP-3 NB (a non-IGF-1 binding form of IGFBP-3 alone is sufficient to mimic the full actions of Compound 49b in protecting against diabetic retinopathy, as well as testing whether IGFBP-3 NB is linked to a restoration of normal insulin signal transduction. Two months after initiation of streptozotocin-induced diabetes, rats received a single intravitreal injection of IGFBP-3 NB plasmid in the right eye. Four days after injection, electroretinogram (ERG analyses were performed prior to sacrifice. Whole retinal lysates from control, diabetic, diabetic + control plasmid, and diabetic+ IGFBP-3 NB were analyzed for IGFBP-3, TNFα, suppressor of cytokine signaling 3 (SOCS3, and insulin receptor signaling partners using Western blotting or ELISA. Data show that a single intraocular injection of IGFBP-3 NB in diabetic animals significantly reduced TNFα levels, concomitant with reductions in IRS-1Ser307, SOCS3, and pro-apoptotic markers, while restoring insulin receptor phosphorylation and increasing anti-apoptotic marker levels. These cellular changes were linked to restoration of retinal function. Our findings establish IGFBP-3 as a pivotal regulator of the insulin receptor/TNFα pathway and a potential therapeutic target for diabetic retinopathy.

  1. Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylenetetrazol model.

    Science.gov (United States)

    Nishida, Namiko; Huang, Zhi-Li; Mikuni, Nobuhiro; Miura, Yoshiki; Urade, Yoshihiro; Hashimoto, Nobuo

    2007-05-01

    Deep brain stimulation (DBS) is a promising therapy for intractable epilepsy, yet the optimum target and underlying mechanism remain controversial. We used the rat pentylenetetrazol (PTZ) seizure model to evaluate the effectiveness of DBS to three targets: two known to be critical for arousal, the histaminergic tuberomammillary nucleus (TMN) and the orexin/hypocretinergic perifornical area (PFN), and the anterior thalamic nuclei (ATH) now in clinical trial. TMN stimulation provided the strong protection against the seizure, and PFN stimulation elicited a moderate effect yet accompanying abnormal behavior in 25% subjects, while ATH stimulation aggravated the seizure. Power density analysis showed EEG desynchronization after DBS on TMN and PFN, while DBS on ATH caused no effect with the same stimulation intensity. EEG desynchronization after TMN stimulation was inhibited in a dose-dependent manner by pyrilamine, a histamine H(1) receptor selective antagonist, while the effect of PFN stimulation was inhibited even at a low dose. In parallel, in vivo microdialysis revealed a prominent increase of histamine release in the frontal cortex after TMN stimulation, a moderate level with PFN and none with ATH. Furthermore, antiepileptic effect of DBS to TMN was also blocked by an H(1) receptor antagonist. This study clearly indicates that EEG desynchronization and the activation of the histaminergic system contributed to the antiepileptic effects caused by DBS to the posterior hypothalamus.

  2. Comparison of premodulated interferential and pulsed current electrical stimulation in prevention of deep muscle atrophy in rats.

    Science.gov (United States)

    Tanaka, Minoru; Hirayama, Yusuke; Fujita, Naoto; Fujino, Hidemi

    2013-04-01

    The goal of this study was to compare the effects of electrical stimulation using pulsed current (PC) and premodulated interferential current (IC) on prevention of muscle atrophy in the deep muscle layer of the calf. Rats were randomly divided into 3 treatment groups: control, hindlimb unloading for 2 weeks (HU), and HU plus electrical stimulation for 2 weeks. The animals in the electrical stimulation group received therapeutic stimulation of the left (PC) or right (IC) calf muscles twice a day during the unloading period. Animals undergoing HU for 2 weeks exhibited significant loss of muscle mass, decreased cross-sectional area (CSA) of muscle fibers, and increased expression of ubiquitinated proteins in the gastrocnemius and soleus muscles compared with control animals. Stimulation with PC attenuated the effects on the muscle mass, fiber CSA, and ubiquitinated proteins in the gastrocnemius muscle. However, PC stimulation failed to prevent atrophy of the deep layer of the gastrocnemius muscle and the soleus muscle. In contrast, stimulation with IC inhibited atrophy of both the gastrocnemius and soleus muscles. In addition, the IC protocol inhibited the HU-induced increase in ubiquitinated protein expression in both gastrocnemius and soleus muscles. These results suggest that electrical stimulation with IC is more effective than PC in preventing muscle atrophy in the deep layer of limb muscles.

  3. [Comparison of the brain pharmacokinetics of nasal tetramethylpyrazine phosphate pH-sensitive in situ gel in normal rats and model rats].

    Science.gov (United States)

    Liu, Hong-Wei; Yan, Yi-Lin; Zhou, Li-Ling

    2012-05-01

    The study is to investigate the brain pharmacokinetics change of nasal tetramethylpyrazine phosphate (TMPP) pH-sensitive in situ gel in normal and model rats. Acute cerebral ischemia rat model was successfully established by middle cerebral artery occlusion (MCAO) method. Both normal and model rats were given nasal TMPP pH-sensitive in situ gel (10 mg x kg(-1)). Perfusates of brain striatum area were collected at each time point by microdialysis. The content of TMPP was determined by HPLC. The pharmacokinetics parameters were calculated by Kinetica 4.4 software at each time point of the brain drug concentration. The main pharmacokinetics parameters of TMPP were fitted with compartments 2. After nasal TMPP pH-sensitive in situ gel the values of C(max) and AUC of both components in brain showed as follows: the value of model group > that of normal group. Significant difference can be observed in the process of brain pharmacokinetics in normal and model rats after giving nasal TMPP pH-sensitive in situ gel.

  4. The Difference in the Profile of Working Memory, Auditory Working Memory, and Spatial Working Memory between Drug, Stimulant, and Methadone Abusers and Normal People

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    Ahmad Alipour

    2015-06-01

    Full Text Available Objective: The present study was an attempt to examine the difference in the profile of working memory, auditory working memory, and spatial working memory between drug, stimulant, and methadone abusers and normal people. Method: This study was a causal-comparative one with between-group comparison methodology. All the individuals addicted to opiates, stimulants, and methadone who had referred to Khomeini treatment centers of the city from September 2013 to February 2014 constituted the statistical population of the study. The number of 154 abusers (54 drug abusers, 50 stimulant abusers, and 50 methadone abusers and the number of 50 normal participants were chosen as the sample of the study by purposive sampling method. The participants responded to Wechsler Memory Scale—third edition (WMS-III. Results: There was a significant difference between the normal group and drug, stimulant, and methadone abusers in terms of working memory, auditory working memory, and spatial working memory. Conclusion: Drug and stimulant use leads to sustained damage in cognitive processes such as working memory. However, research indicates that these cognitive processes will improve with the passage of time.

  5. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats.

    Science.gov (United States)

    Ríos-Lugo, María J; Cano, Pilar; Jiménez-Ortega, Vanesa; Fernández-Mateos, María P; Scacchi, Pablo A; Cardinali, Daniel P; Esquifino, Ana I

    2010-11-01

    Melatonin effect on body weight progression, mean levels and 24-hr pattern of circulating adiponectin, leptin, insulin, glucose, triglycerides and cholesterol were examined in rats fed a normal or a high-fat diet. In experiment 1, rats fed a normal diet were divided into two groups: receiving melatonin (25 μg/mL drinking water) or vehicle for 9 wk. In experiment 2, animals were divided into three groups: two fed with a high-fat diet (35% fat) and melatonin (25 μg/mL) or vehicle in drinking water for 11 wk, while a third group was given a normal diet (4% fat). At the end of experiments, groups of eight rats were killed at six different time intervals throughout a 24-hr period. Melatonin administration for 9 wk decreased body weight gain from the 3rd wk on without affecting food intake. A significant reduction in circulating insulin, glucose and triglyceride mean levels and disrupted daily patterns of plasma adiponectin, leptin and insulin were observed after melatonin. In high fat-fed rats, melatonin attenuated body weight increase, hyperglycemia and hyperinsulinemia, as well as the increase in mean plasma adiponectin, leptin, triglycerides and cholesterol levels. The high-fat diet disrupted normal 24-hr patterns of circulating adiponectin, insulin and cholesterol, the effects on insulin and cholesterol being counteracted by melatonin. Nocturnal plasma melatonin concentration in control and obese rats receiving melatonin for 11 wk attained values 21-24-fold greater than controls. The results indicate that melatonin counteracts some of the disrupting effects of diet-induced obesity in rats. © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

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

    Science.gov (United States)

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

    2007-02-01

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

  7. Effects of remifentanil on intracellular Ca2+ and its transients induced by electrical stimulation and caffeine in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ye; Michael G. Irwin; LI Rui; CHEN Zhiwu; Tak-Ming Wong

    2009-01-01

    Background Preconditioning with remifentanil confers cardioprotection. Since Ca2+ overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca2+ ([Ca2+]I) and its transients induced by electrical stimulation and caffeine, which reflects Ca2+ handling by Ca2+ handling proteins, in rat ventricular myocytes. Methods Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca]I was determined by spectrofluorometry. Remifentanil at 0.1-1000 μg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca2+]I, and the amplitude, time resting and 50% decay (t50) of both transients induced by electrical stimulation (E[Ca2+]I) and caffeine (C[Ca2+]I) were determined.Results Remifentanil (0.1-1000.0 μg/L) decreased the [Ca2+]I in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t50 of both transients dose-dependently.Conclusion Remifentanil reduced the [Ca2+]I and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

  8. The left ventricular contractility of the rat heart is modulated by changes in flow and a1-adrenoceptor stimulation

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    P.F. Vassallo

    1998-10-01

    Full Text Available Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP and flow as well as on a1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10 submitted to phenylephrine (PE stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo a1-adrenergic stimulation increases left ventricular-developed pressure (Pa1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.

  9. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    Science.gov (United States)

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

  10. Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem.

    Science.gov (United States)

    Rijkers, K; Majoie, H J M; Aalbers, M W; Philippens, M; Doenni, V M; Vles, J S H; Steinbusch, H M W; Moers-Hornikx, V M P; Hopkins, D A; Hoogland, G

    2012-12-01

    Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygda