The role of serotonin in ephedrine-induced stereotypy and hypermotility.

The influence of serotonin agents on stereotypy and hypermotility induced with ephedrine was studied. P-Chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, had no influence on stereotypy. In reserpinized animals, this reaction was intensified only after high doses of ephedrine (100 and 120 mg/kg), but the precursor of 5-HT synthesis, tryptophan, strongly antagonized stereotypy. Ephedrine-induced hypermotility in mice and rats was potentiated by PCPA. It is suggested that serotonin ephedrine-induced effects, similarly to previous observations with amphetamine.     

Time- and dose-related influence of dexamethasone on morphine-induced hypermotility in mice

The effect of interaction between dexamethasone (DEX) and morphine on locomotor activity in mice was investigated. DEX alone (1.0 and 10 mg/kg i.p.) did not affect the locomotor activity of mice when injected immediately before the beginning of the session. DEX (1.0 mg) injected two hours before the session did not modify the activity of mice whereas the higher dose (10 mg) increased it. Morphine alone (30 mg/kg i.p.) induced a consistent increase in the locomotor activity. DEX (1.0 mg) injected at the same time as morphine reduced the morphine hypermotility, whereas that injected two hours before morphine had no influence on morphine hypermotility. DEX (10 mg) consistently potentiated the morphine hypermotility both when administered together and two hours before morphine. We conclude that DEX exerts an important time-and dose-related influence on morphine-induced hyperactivity in mice.     

A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence

Keratinocytes become migratory to heal wounds, during early neoplastic invasion, and when undergoing telomere-unrelated senescence in culture. All three settings are associated with expression of the cell cycle inhibitor p16INK4A (p16) and of the basement membrane protein laminin 5 (LN5). We have investigated cause-and-effect relationships among laminin 5, p16, hypermotility, and growth arrest. Plating primary human keratinocytes on the gamma2 precursor form of laminin 5 (LN5') immediately induced directional hypermotility at approximately 125 microm/hour, followed by p16 expression and growth arrest. Cells deficient in p16 and either p14ARF or p53 became hypermotile in response to LN5' but did not arrest growth. Plating on LN5' triggered smad nuclear translocation, and all LN5' effects were blocked by a transforming growth factor (TGF) beta receptor I (TGFbetaRI) kinase inhibitor. In contrast, plating cells on collagen I triggered a TGFbetaRI kinase-independent hypermotility unaccompanied by smad translocation or growth arrest. Plating on control surfaces with TGFbeta induced hypermotility after a 1-day lag time and growth arrest by a p16-independent mechanism. Keratinocytes serially cultured with TGFbetaRI kinase inhibitor exhibited an extended lifespan, and immortalization was facilitated following transduction to express the catalytic subunit of telomerase (TERT). These results reveal fundamental features of a keratinocyte hyper-motility/growth-arrest response that is activated in wound healing, tumor suppression, and during serial culture.     

Time- and dose-related influence of dexamethasone on morphine-induced hypermotility in mice

The effect of interaction between dexamethasone (DEX) and morphine on locomotor activity in mice was investigated. DEX alone (1.0 and 10 mg/kg i.p.) did not affect the locomotor activity of mice when injected immediately before the beginning of the session. DEX (1.0 mg) injected two hours before the session did not modify the activity of mice whereas the higher dose (10 mg) increased it. Morphine alone (30 mg/kg i.p.) induced a consistent increase in the locomotor activity. DEX (1.0 mg) injected at the same time as morphine reduced the morphine hypermotility, whereas that injected two hours before morphine had no influence on morphine hypermotility. DEX (10 mg) consistently potentiated the morphine hypermotility both when administered together and two hours before morphine. We conclude that DEX exerts an important time-and dose-related influence on morphine-induced hyperactivity in mice.

     

Dopamine metabolism in depressions, psychoses, and Parkinson's disease: the problem of the specificity of biological variables in behaviour disorders.

The probenecid technique was used in study of the central dopamine DA metabolism in patients with depressions, psychotic disorders, and Parkinson's disease. The disturbances found were neither nosologically nor syndromally specific, but appeared to be symptom-specific. Decreased DA turnover was associated with hypomotility, and increased DA turnover with hypermotility. Decreased DA turnover was probably related aetiologically to the hypomotility: the symptoms subsided after replenishment of the DA deficiency. The relation between increased DA turnover and hypermotility is still under investigation. In view of the findings obtained, a plea is made for the development of a functional psychopathology, in which psychiatric syndromes are "dissected" into their constituent psychological dysfunctions. This development is expected to stimulate human brain and behaviour research. It can be achieved only by intensive collaboration between psychiatrists and experimental psychologists.     

Incidence of sleep apnea in a presumably healthy working population: a significant relationship with excessive daytime sleepiness

Seventy-eight workers, drawn from a population of 1502 presumably healthy working men who were interviewed about sleep habits and sleep disorders, underwent polygraphic recordings for at least 1 night. A significant association was found between the complaint of excessive daytime sleepiness and the incidence of sleep apnea. Workers with more than 10 apneas per hour of sleep complained significantly more about loud snoring, hypermotility in sleep, and frequent headaches. They had significantly more ENT findings and hypertension.     

Incidence of sleep apnea in a presumably healthy working population: a significant relationship with excessive daytime sleepiness

Seventy-eight workers, drawn from a population of 1502 presumably healthy working men who were interviewed about sleep habits and sleep disorders, underwent polygraphic recordings for at least 1 night. A significant association was found between the complaint of excessive daytime sleepiness and the incidence of sleep apnea. Workers with more than 10 apneas per hour of sleep complained significantly more about loud snoring, hypermotility in sleep, and frequent headaches. They had significantly more ENT findings and hypertension.     

Synthesis and pharmacologic properties of pyridoyl derivatives of 3-methylaminoindole 2-methyltryptamine and isotryptamine.

Six new pyridoyl derivatives of 3-methylaminoindole, 2-methyltryptamine and isotryptamine were synthesized by condensation with chlorides of nicotinic and isonicotinic acids. The central action of these compounds seems to depress the central nervous system, as they reduce spontaneous motility (I, II, IV, V, VI) and amphetamine hypermotility (II, IV, V), prolong hexobarbital sleeping time (II, IV, V, VI), display analgesic action in the "writhing test" (all compounds) and in the "hot plate test" (IV, V). The compounds do not change body temperature and display no anticonvulsant action.     

外源性硫化氢及K_(ATP)通道对大鼠慢性应激结肠高动力的调节

目的:研究外源性硫化氢(hydrogen sulfide,H2S)及ATP敏感性钾通道(ATP-sensitive potassium channels,KATP)在慢性应激结肠高动力中的作用。方法:制作慢性避水应激(water avoidance stress,WAS)和假避水应激(sham water avoidance stress,SWAS)大鼠模型,观察2组大鼠结肠肌条的收缩活性以及硫氢化钠(Na HS)和格列本脲预处理后对2组大鼠结肠肌条收缩影响并计算Na HS的半数抑制浓度(half maximal inhibitory concentration,IC50),使用免疫荧光及Western blotting法观察KATP通道各亚基在结肠中的分布及表达。结果:WAS组结肠肌条收缩活性明显高于SWAS组;Na HS浓度依赖性抑制2组大鼠纵行肌(longitudinal muscle,LM)和环形肌(circular muscle,CM)的收缩;WAS组LM和CM的Na HS IC50分别为0.2033 mmol/L和0.1438 mmol/L,均明显低于SWAS组(P0.01);格列本脲明显增加2组大鼠肌条Na HS IC50(P0.01);Kir6.1、Kir6.2和SUR-2B在2组大鼠结肠固有肌细胞膜均有分布;WAS组(去除黏膜及黏膜下层后)Kir6.1和SUR2B蛋白表达高于SWAS组(P0.01)。结论:H2S外源性供体Na HS对慢性应激结肠高动力具有潜在的治疗作用。KATP通道亚基Kir6.1/SUR2B表达增加可能是慢性应激结肠动力紊乱的一种适应性反应。     

Central action of drugs acting on the cholinergic muscarinic receptor. II. Influence of ecothiopate administered into the lateral cerebral ventricle on behavior in rats.

Ecothiopate (Etp), 10 mug injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, inhibited amphetamine-induced hypermotility and stereotypy, prolonged hexobarbital anesthesia and did not induce catalepsy. These behavioral symptoms were accompanied by lowered level of NA and elevated levels of 5-HT and 5-HIAA in the brain. No change in levels of DA were noted. Smaller doses (0-1 and 1 mug) had virtually no influence on behavior of the animals. The dose of 1 mug caused a rise in levels of 5-HIAA in the brain, but had no influence on levels of NA, DA and 5-HT.     

Diffuse esophageal intramural pseudodiverticulosis and nutcracker esophagus in a 54-year-old man

Summary Esophageal intramural pseudodiverticulosis, which was first described by Mendl et al. in 1960, is characterized by multiple small flaskshaped outpouchings in the esophageal wall. The pseudodiverticula represent dilated excretory ducts of deep mucous glands in the esophagus. The etiology of this rare condition is unknown. Hiatal hernias, gastroesophageal reflux, esophageal strictures, Candida esophagitis, herpes esophagitis, diabetes mellitus, and chronic alcoholism have been found associated with intramural pseudodiverticulosis. We report the second case of esophageal hypermotility in intramural pseudodiverticulosis.Abbreviations cm centimeter - kg kilogram - LES lower esophageal sphincter - ml/min milliliter per minute - mm millimeter - mmHg millimeter of mercury - U/l unit per liter     

Central action of drugs acting on the cholinergic muscarinic receptor I. Influence of cholinomimetic drugs administered into the lateral cerebral ventricle on behavior in rats.

Carbachol (CCh), physostigmine (Pht) and pilocarpine (Pil) injected into the lateral cerebral ventricle (ivtr), diminished spontaneous motility and open-field performance, lowered body temperature, depressed amphetamine-induced hypermotility, and inhibited amphetamine stereotypy. On the other hand, they had no effect on duration of hexobarbital anesthesia, except Pil, which slightly prolonged it, or on the action of threshold dose of pentetrazole and maximal electroshock. The compounds raised levels of "free" and "total" ACh, but not those of "bound" ACh. Level of NA in the brain was decreased, while level of DA was unaltered. These results are further evidence of an inhibitory influence of cholinomimetic drugs on behavior in animals.     

The trigeminocardiac reflex – a comparison with the diving reflex in humans

The trigeminocardiac reflex (TCR) has previously been described in the literature as a reflexive response of bradycardia, hypotension, and gastric hypermotility seen upon mechanical stimulation in the distribution of the trigeminal nerve. The diving reflex (DR) in humans is characterized by breath-holding, slowing of the heart rate, reduction of limb blood flow and a gradual rise in the mean arterial blood pressure. Although the two reflexes share many similarities, their relationship and especially their functional purpose in humans have yet to be fully elucidated. In the present review, we have tried to integrate and elaborate these two phenomena into a unified physiological concept. Assuming that the TCR and the DR are closely linked functionally and phylogenetically, we have also highlighted the significance of these reflexes in humans.     

Haloperidol discontinuation in a herpes simplex encephalitis patient with atypical abnormal movements using the herbal medicine Ukgansan-gami: A case report

Recently, the herbal medicine Ukgansan (Yigansan in China, Yokukansan in Japan) was reported to be effective in the management of movement disorders. We report the case of a 62-year-old woman with herpes simplex encephalitis exhibiting atypical abnormal movements in the chronic stage. While controlling the abnormal movements with haloperidol, an antipsychotic agent, we prescribed Ukgansan-gami, an extract of a variant of Ukgansan, at a dose of 12 g/day to prevent the recurrence of abnormal movements and allow for the discontinuation of haloperidol. The patient was successfully treated with Ukgansan-gami, with no further recurrence of symptoms, making the use of haloperidol no longer necessary. The potential mechanism of action of Ukgansan involves the inhibition of nervous system hyperexcitability through the suppression of glutamate sodium channels, as well as attenuation of hypermotility through serotonin regulation. The present case suggests that herbal medicine therapy was likely to be an alternative to antipsychotics.     

The role of embryo movement in the development of the furcula

The pectoral girdle is a complex structure which varies in its morphology between species. A major component in birds is the furcula, which can be considered equivalent to a fusion of the paired clavicles found in many mammals, and the single interclavicle found in many reptiles. These elements are a remnant of the dermal skeleton and the only intramembranous bones in the trunk. Postnatally, the furcula plays important mechanical roles by stabilising the shoulder joint and acting as a mechanical spring during flight. In line with its mechanical role, previous studies indicate that, unlike many other intramembranous bones, furcula growth during development can be influenced by mechanical stimuli. This study investigated the response of individual aspects of furcula growth to both embryo immobilisation and hypermotility in the embryonic chicken. The impact of altered incubation temperature, which influences embryo motility, on crocodilian interclavicle development was also explored. We employed whole‐mount bone and cartilage staining and 3D imaging by microCT to quantify the impact of rigid paralysis, flaccid paralysis and hypermobility on furcula growth in the chicken, and 3D microCT imaging to quantify the impact of reduced temperature (32–28 °C) and motility on interclavicle growth in the crocodile. This revealed that the growth rates of the clavicular and interclavicular components of the furcula differ during normal development. Total furcula area was reduced by total unloading produced by flaccid paralysis, but not by rigid paralysis which maintains static loading of embryonic bones. This suggests that dynamic loading, which is required for postnatal bone adaptation, is not a requirement for prenatal furcula growth. Embryo hypermotility also had no impact on furcula area or arm length. Furcula 3D shape did, however, differ between groups; this was marked in the interclavicular component of the furcula, the hypocleideum. Hypocleideum length was reduced by both methods of immobilisation, and interclavicle area was reduced in crocodile embryos incubated at 28 °C, which are less motile than embryos incubated at 32 °C. These data suggest that the clavicular and interclavicle components of the avian furcula respond differently to alterations in embryo movement, with the interclavicle requiring both the static and dynamic components of movement‐related loading for normal growth, while static loading preserved most aspects of clavicle growth. Our data suggest that embryo movement, and the mechanical loading this produces, is important in shaping these structures during development to suit their postnatal mechanical roles.     

An experimental study of gastrointestinal motility during chronic large bowel obstruction]

Gastrointestinal motility and plasma PYY levels were investigated under chronic progressive large bowel obstruction in dogs. The obstruction device was applied around the descending colon at a laparotomy and gastrointestinal motility was recorded with strain gauge force transducers in the conscious state. Complete obstruction occurred at 26 days (21-33 days). The duration of postprandial interruption of motor complex (DIMC) in the antrum and duodenum were prolonged progressively, at partial obstruction (17.7 +/- 2.7 hr; p less than 0.05) and complete obstruction (23.0 +/- 4.0 hr; p less than 0.01) vs in control (13.7 +/- 1.9 hr), while DIMC in the small bowel showed no significant changes. Progressive obstruction caused hypermotility in the proximal colon to the obstruction and hypomotility in the distal colon. These dysmotility were improved after resection of the obstructed segment and anastomosis. Plasma PYY levels in the fasting state showed no significant increase at complete obstruction (42.6 +/- 14.5 pmol/l) vs in control (32.9 +/- 10.2 pmol/l).     

Nitric oxide regenerates the normal colonic peristaltic activity in mdx dystrophic mouse

We demonstrated in vitro that the colonic peristaltic activity is modified in dystrophin-deficient mdx mouse indicating a defect in the enteric nervous system (ENS). Since nitric oxide (NO) has been proposed as a putative inhibitory mediator of ENS, here we have examined the effects of both L-Arginine (L-Arg) and Nomega-nitro-L-arginine methyl ester (L-NAME) on the peristaltic activity of mdx mouse distal colon. The motor pattern of colonic segment showed irregular peristaltic waves. L-Arg (10(-7) - 10(-5) M) induced the peristaltic activity to slow down. At a concentration of 10(-5) M, L-Arg produced hypomotility, characterised by a decrease in amplitude, frequency and ejected fluid volume. Conversely, L-NAME elicited hypermotility, this effect being reversed once again by the subsequent addition of L-Arg. Interestingly the addition of 10(-5) M L-Arg to the organ bath led to the normal progression, in an oral to aboral direction, of 90% of the peristaltic waves. This last result strongly suggests that exogenous application of L-Arg restores the integrative circuits of the ENS responsible for programming and co-ordinating peristaltic activity in the distal colon of mdx mouse.     

Effects of estradiol replacement in ovariectomized rats on conditioned avoidance responses and other behaviors

The acquisition of conditioned avoidance responses along with spontaneous behaviors were studied in ovariectomized rats. Fourteen days after ovariectomy, they were injected subcutaneously with one of the following doses of estradiol benzoate: 0.2, 2 or 20 microgram/rat. Behavioral tests were applied 3, 24, 48 or 72 hours after estradiol treatment. Although estradiol 2 microgram/rat induced a decrease in acquisition of conditioned avoidance responses at all times tested, this effect was maximum at 48 h. Estradiol 0.2, and 20 microgram/kg decreased and stimulated, respectively, the acquisition performance, as tested 3 h after injection. All doses increased global motility and rearing behavior. This hypermotility disappeared at 24 h, but it was observed again at 48 and 72 h after estradiol 0.2 and 20 microgram/rat. The hormone also induced an increase in head shaking and a decrease in grooming. Although the behavioral changes are more significant in presence of very low serum levels of estradiol, they seem to be triggered by the previous increase in the estradiol levels. The possible sites and mechanisms of action of estradiol on behavior are discussed.     

Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity

Gamma-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA) provide innervation to cortical and subcortical regions of the brain. To solidify the importance of these VTA GABA neurons in behavioral function, we employed the neurotoxin dermorphin-saporin (DS) to selectively lesion VTA GABA neurons prior to assessing spontaneous motor activity. Rats were bilaterally microinfused with DS (1.0 or 2.0 pmol/200 nl/side) or blank-saporin control (BS, 200 nl/side) into the VTA. Seven days later, DS-treated rats exhibited significantly elevated motility in comparison with BS-treated rats; this elevated motility normalized by Day 14 following pretreatment with 1.0 pmol of DS but was sustained on Day 14 after pretreatment with 2.0 pmol of DS. A selective loss of VTA GABA neurons on Day 14 was demonstrated through reduced expression of mRNA for glutamic acid decarboxylase-67 and micro-opioid receptor, but not tyrosine hydroxylase (a dopamine neuron marker), in the VTA. Thus, a dose- and time-related selective loss of VTA GABA neurons was accomplished using this novel neurotoxin. This loss of GABA VTA neurons was associated with hypermotility, further supporting their important regulatory role in the generation of behavior.     

Migratory activation of primary cortical microglia upon infection with Toxoplasma gondii

Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites in situ in the brain parenchyma. Toxoplasma gondii tachyzoites were allowed to infect primary microglia and astrocytes in vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia, Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet Toxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells in vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as "Trojan horses," paradoxically facilitating dissemination of Toxoplasma within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.