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Methods of measuring gallbladder motor functions--the need for standardization: scintigraphy.

Emptying the gallbladder is part of the complex process of food digestion. The gallbladder interacts with other gastrointestinal organs and its movements are coordinated and modified by functions of the stomach, intestine and pancreas. Many factors can modify gallbladder motility, for example, sex and age of the subject, their body mass, the kinds of food ingested and stimulus used. The assumption that the gallbladder progressively empties during meals and refills during fasting is incorrect. Using a combination of ultrasonography and cholescintigraphy, it is possible to measure absolute and net gallbladder emptying. In this way we demonstrated that the gallbladder begins to refill immediately after emptying begins, and the difference between net and absolute emptying of the gallbladder indicates the refilling of bile and provides a measure of bile turnover rate, an accurate index to assess gallbladder motility.

Cholecystokinin↗

Phenotypically selected mutations in myosin's actin binding domain demonstrate intermolecular contacts important for motor function.

Here, we biochemically characterize Dictyostelium myosin II mutants that were previously phenotypically selected following random mutagenesis and shown to lie in the actin binding domain [Patterson, B., & Spudich, J. A. (1996) Genetics 143, 801-810]. We show that the conditional loss of myosin-dependent activity in vivo, which results from the mutations E531Q, P536R, and R562L, is likely due to the loss of important contacts with actin. Purified wild-type and mutant myosin subfragments 1 (S1), expressed in Dictyostelium, are alike in binding to actin and releasing it in an ATP-dependent manner. Furthermore, the rates of ATP hydrolysis without actin are similar for the mutant and wild-type S1s. Thus, the mutations in the actin binding site have little effect on ATP binding or product release in the absence of actin. All three mutants, however, have impaired actin-activated ATPase activity, with apparent second-order rate constants for actin interactions that are 4-25-fold smaller than that of wild-type S1 at 30 degrees C. The mutations also cause defects in the ability to move actin, as measured by in vitro motility assays of full-length myosins. On the basis of motility of a mixture of wild-type and mutant myosins, there appears to be at least two classes of mutations, with the primary defect in either a weak or a strong actin binding state. In summary, the activities in vitro of myosins with mutations in the actin binding site suggest losses of important contacts with actin.

Actins↗

Modulation of actomyosin motor function by 1-hexanol.

This study examines the effects of 1-hexanol as a perturbing agent on actomyosin ATPase and its related functions in the concentration range between 0 and 20 mM. In this range the denaturation of myosin subfragment 1 (S1), as measured by the inactivation rate of its K-EDTA-ATPase, and depolymerization of F-actin were insignificant. Major findings showed that hexanol had the following effects which were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10-fold at 20 mM) without greatly affecting the enhancement of tryptophan fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity; (c) an increase in the affinity of S1 for actin in the presence of ATP and a decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in the sliding velocity of actin filaments in in vitro motility assays with myosin, and (e) a decrease in isometric tension of single skinned muscle fibers. Thus, the effects of hexanol on actomyosin interaction are distinct for the weak and strong binding states, consistent with a change in the hydrophobic interaction in the interface between myosin and actin accompanying the transition from the weak to the strong binding state. Hexanol also accelerates the Pi release from S1.ADP.Pi, which is the transition step from the weak to the strong binding state. The fact that hexanol accelerates Pi release suggests that this alcohol perturbs the S1.ADP.Pi conformation. We speculate that this intermediate-specific structural perturbation is related to the inhibition of the maximum actin-activated ATPase, in vitro motility, and isometric tension.

Actins↗

Review article: control of gall-bladder motor function.

Muscular contraction of the gall-bladder is the primary determinant of bile delivery into the duodenum. Where bile goes following its secretion by the liver depends upon a co-ordinated series of pressure interrelations between the hepatic secretory pressure at the entrance to the biliary system, a low pressure conduit, and the pressure differences between the gall-bladder, cystic duct and sphincter of Oddi. During fasting, the relatively higher tone in the sphincter of Oddi fosters the entry of bile into the gall-bladder. The gall-bladder accommodates this influx without an increase in intravesicular pressure through its compliance or distensibility, which consists of active muscle relaxation and passive fibroelastic components. The concentrating function of the gall-bladder keeps the volume small. Once about every 120 min during the interdigestive period, gall-bladder emptying occurs coincident with intense duodenal contractions; all part of the migratory myoelectric complex. This helps maintain the enterohepatic circulation of bile salts. Motilin, which mediates these events during fasting, acts by stimulating intrinsic cholinergic nerves. Cholecystokinin is the major determinant of gallbladder emptying with eating. Cholecystokinin acts through pre-ganglionic cholinergic nerves, to initiate gall-bladder contraction. Agonists like cholecystokinin and acetylcholine cause contraction of gall-bladder smooth muscle through signal transduction, which increases intracellular calcium levels and so initiates the contractile machinery. Cholecystokinin also acts on the sphincter of Oddi via pre-ganglionic cholinergic nerves to release vasoactive intestinal polypeptide and nitric oxide, and so lower tone. These events are co-ordinated with motility and secretory events in the upper gastrointestinal tract, delivering bile at appropriate times into the duodenum.

Cholecystokinin↗

Review: low caloric intake and gall-bladder motor function.

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall-bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall-bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall-bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall-bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall-bladder stasis, as a consequence of reduced gall-bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall-bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall-bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall-bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall-bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.

Bile Acids and Salts↗

Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects.

BACKGROUND: Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of gamma-aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors. AIM: To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro-oesophageal reflux. METHODS: Thirteen healthy subjects underwent 2-h post-prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo. RESULTS: Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. 9.9 +/- 2.0 mmHg after placebo, P<0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 +/- 1.0/h vs. 8.2 +/- 0.9/h after placebo), the number of reflux episodes or gastro-oesophageal reflux. CONCLUSIONS: Non-selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors.

Adult↗

Social dancing: a way to support intellectual, emotional and motor functions in persons with dementia.

Dementia causes serious impairments and the inability to perform those activities which give meaning to a person's life. Therefore, these persons are in need of professional nursing care interventions as well as a special supporting environment. In this study, social dancing has been regarded as a nursing intervention that supports persons with dementia in nursing home settings. The aim was to find out how persons with dementia functioned in social dance sessions, in order to understand the reasons behind the use of social dancing as a nursing intervention in a nursing home setting. Six persons with dementia were videotaped during four dance sessions in one nursing home. The qualitative content analyses were carried out deductively, using a guide developed from the variables in the Gottfries, Bråne and Steen rating scale (GBS scale). The findings show that, for persons with dementia, retained abilities were prominent in dancing. It was obvious that social dancing was supportive and seemed to have meaning to both patients and their carers. Social dancing seems to be a nursing intervention that supports patients' positive feelings, communication and behaviour. The carers' preunderstanding of the patients' levels of dementia and the wholeness of the situation was of importance.

Aged↗

Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function.

The present experiments evaluate the effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64 kDa or less). In ketamine-anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg-1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred. In the cat, an o-raffinose cross-linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.

Animals↗

Effect of training on muscle strength and motor function in the elderly.

Overall muscle strength and mass decline 30-50% between the ages of 30 and 80. The loss of muscle mass, the so called sarcopenia, accounts for most of the observed loss of strength. A reduced specific muscle force has also been observed but its contribution to the decrease in strength with age remains unclear. The loss of muscle tissue is due to a decrease in the number of muscle fibres and atrophy of the type II muscle fibres. The declining strength reduces the capacity to carry out basic activities of daily life and puts people at risk for falls and dependence. Resistive strength training greatly increases muscle strength even in very old people. It produces muscle fibre hypertrophy and improves neural factors involved in force production. The recovered strength in turn enhances the physical performance and allows a more active and independent life towards the end of the life span.

Adult↗

Obesity does not increase effects of synthetic ghrelin on human gastric motor functions.

BACKGROUND & AIMS: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. METHODS: After intravenous bolus synthetic human ghrelin (0.33 mug/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined (99m)Tc-single-photon emission computed tomography and scintigraphy ((111)In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. RESULTS: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 +/- 4 kg/m(2)) and 13 female normal-weight (BMI, 22 +/- 2 kg/m(2)) subjects of similar ages, ghrelin increased GH levels (15.0 +/- 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. CONCLUSIONS: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.

Adolescent↗

Cerebral magnetic resonance imaging (MRI) and mental and motor function of very low birth weight infants at one year of corrected age.

Thirty-one (77.5%) of a year cohort of 40 surviving infants with birth weight < 1500 grams were seen on follow-up examination at one year of corrected age. At neurological evaluation 20 infants were normal (Group 1), seven infants were considered at risk (Group 2), and four infants had cerebral palsy (Group 3). Assessment on the Bayley Scales gave significantly lower mean scores in Group 3 compared with Group 1, both on the Mental Index (63 versus 102, p < 0.001) and on the Psychomotor Index (PDI) (60 versus 94, p < 0.005). Mean PDI score in Group 2 was significantly lower than in Group 1 (74 versus 94, p < 0.005). Cerebral MRI was performed in 27 infants. Of the 19 infants in Group 1 examined with MRI, 14 infants showed deviating changes in both myelin deposition and maturation (2). In all 14 infants the central occipital white matter was affected and in three infants also the centrum semiovale, both areas correspond to predilection sites for periventricular leukomalacia (PVL). Five infants had irregular shape of the occipital horns of the lateral ventricles. These findings may also represent the end stages of PVL (4). Only four out of seven infants were examined with MRI in Group 2. However, three infants had deviating myelination and three had irregular shape of the posterior horns. In Group 3 all infants were examined with MRI and all had deviating myelination and irregular and slightly dilated posterior horn. There was a significant correlation between abnormally dilated occipital horns seen with MRI, and cerebral palsy and low scores on the Denver and the Bayley tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy↗

Effects of cisapride on symptoms and postcibal small-bowel motor function in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.

Adult↗

Improved motor function in tetraplegics following neuromuscular stimulation-assisted arm ergometry.

The effectiveness of neuromuscular stimulation (NMS)-assisted arm ergometry for strengthening triceps brachii was evaluated in 34 cervical spinal cord injured persons. Group I (n = 12) received eight weeks of NMS-assisted ergometry. Group II (n = 11) received four weeks of NMS-assisted ergometry followed by four weeks of arm ergometry alone. Group III (N = 11) received only arm ergometry (control group). Seventeen of 24 muscles in Group I subjects had improved manual muscle test scores after eight weeks, compared with 10 of 22 Group II muscles and five of 22 Group III muscles. Including only muscles with initial scores < or = 3, Group I demonstrated significant improvements versus Group III after four weeks (p < .003) and after eight weeks (p < .0005) of exercise. A difference was also found between Groups II and III (p < .03) after eight weeks. These results suggest that NMS-assisted ergometry is effective for strengthening voluntary triceps muscle contractions in tetraplegics.

Adolescent↗

Serotonin-related enhancement of recovery of hind limb motor functions in spinal rats after grafting of embryonic raphe nuclei.

Recently, we demonstrated improvements in hind limb locomotor-like movements following grafting of embryonic raphe nuclei cells into the spinal cord below the level of total transection in adult rats. The purpose of the present study was to clarify whether this improvement was due to newly established serotonergic innervation between the graft and the host. Two months after intraspinal grafting of the embryonic raphe nuclei, the spinalized rats, when put on a treadmill, could be induced to walk with regular alternating hind limb movements with the plantar contact with the ground during the stance phase, and ankle dorsiflexion during the swing phase of each step cycle. In the same situation the spinal rats, that did not receive the graft, were not able to initiate the dorsiflexion of the ankle joint during the swing phase and very often the dorsal surface of the foot was dragged along the ground. Intraperitoneal application of directly acting 5-HT2 antagonist Cyproheptadine (1 mg/kg) impaired reversibly the hind limb locomotor-like movements in grafted rats. This impairment lasted for 2-3 h. The same procedure in control rats did not markedly alter the hind limb locomotor-like movements. The effect of Cyproheptadine in grafted rats was reversed by i.p. injections of the 5-HT2 agonist Quipazine (0.5 mg/kg). These results show that the graft-induced restitution of hind limb locomotor abilities in adult spinal rats is brought about by the new serotonergic innervation of the host spinal cord circuitry from the grafted neurons and is mediated by 5-HT2 receptors.

Animals↗