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Supersensitivity to electrical stimulation for assessing physical dependence on opioids in isolated tissues.

The use of the guinea pig ileum (GPI) and mouse vas deferens (MVD) to quantify opiate tolerance and physical dependence in the same preparation was examined. In the GPI, tolerance to and physical dependence on various opiates were induced by direct incubation with an agonist and tolerance and abstinence were assessed after its rapid removal by extensive washing. Dependence, as evidenced by an increase in twitch height and after removal of the agonist as compared to that before incubation, provided an index of the degree of physical dependence. The extent of the supersensitive response after agonist removal was noted to be related directly to the agonist concentration and the degree of tolerance development. Furthermore, the supersensitive response was found to be stereospecific, naloxone reversible and preferentially mu receptor-mediated. Likewise, tolerance to opiates could be demonstrated in the MVD by direct incubation with an agonist. Unlike the GPI, rapid removal of the agonist by washing did not produce a supersensitive response to electrical stimulation. However, a supersensitive response was demonstrable in the presence of naloxone. Thus, after a tolerant/dependent state was induced by incubation of the vas with a predetermined dose of [D-Ala2, D-Leu5]enkephalin that completely abolished the twitch response, the subsequent addition of naloxone resulted in a supersensitive response to electrical stimulation that was concentration-dependent. The maximum twitch response in the presence of naloxone, compared to that obtained before incubation with the agonist, provided an index of the extent of dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Physical properties of stimulated and unstimulated tears.

It has long been assumed that unstimulated tears are more thoroughly equilibrated with epithelial secretions than stimulated tears, since they are in contact with tarsal, bulbar and corneal surfaces for longer. It was also believed from results with model solutions that soluble mucin is responsible for the observed surface tension and viscosity of tears. If longer contact means more mucin is dissolved in the aqueous tears, then the surface activity (surface tension lowered by mucin) and viscosity (raised by mucin) of tears should therefore be enhanced in unstimulated over stimulated tears. Pools of stimulated and minimally-stimulated tears were collected from a group of healthy adult volunteers by glass capillary. Viscosities were measured in the Contraves Low Shear 30 rheometer over the range of shear rates 0-130 sec-1. Surface tension was measured in the collection capillaries by a micro-technique, before and after refrigerated storage. Both surface tension and viscosity were determined for a variety of tear proteins and mucins. No significant difference was found between the viscosity/shear rate plots of stimulated and unstimulated tear samples. The viscosities of solutions of individual tear proteins were low, except for the combination of lysozyme and secretory IgA. Surface tensions were also similar in both cases, and unchanged by storage at room temperature or refrigeration, indicating no significant loss of surface-active material by adsorption on the capillary walls. Results with model mucin solutions gave a variety of results indicating either little surface activity or losses due to wall adsorption. Tear proteins, individually or in combination, did not lower surface tension to the level of tears. Tear viscosity seems not to depend on the level of dissolved mucins. This suggests either that a constant level of these is picked up even by short-term contact with ocular surfaces, or that viscosity arises from currently unknown materials which vary little with tear flow rate. This type of shear-dependent viscosity is most easily simulated in model solutions with polyionic linear macromolecules, including mucins. The contribution of individual proteins to overall viscosity is small, but combinations including lysozyme show tear-like characteristics, and may indicate that proteins whose concentration is relatively independent of tear flow rate combine with other tear components (possibly including mucins or lipids) to produce their full effect on tear viscosity. The surface tension results suggest that mucins are not of primary importance. Theories of tear film structure and performance need revision.

Adult↗

Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers.

Hormone responses to injection of corticotropin-releasing hormone following bicycle ergometry and psychological stress were studied in ten habitual smokers and ten nonsmokers. Compared to injection of saline, significant increases were found in adrenocorticotropin, prolactin, growth hormone, total serum cortisol, and salivary cortisol under all three stimulations except for salivary cortisol under ergometry. Furthermore, the smokers showed significant elevations of all five hormones investigated following the smoking of two cigarettes of the subject's preferred brand. Comparisons of hormone responses between smokers and nonsmokers revealed a general trend towards stronger responses in nonsmokers. However, due to the small number of subjects investigated and considerable variation in the individual hormone responses these differences reached statistical significance only for growth hormone responses following ergometry and salivary cortisol responses after psychological stress. In addition, the circadian rhythm of salivary cortisol was measured on two occasions between 9 a.m. and 9 p.m. in the subject's natural environment. The typical circadian pattern of decreasing cortisol levels was observed, with no significant differences between smokers and nonsmokers. We conclude that chronic nicotine consumption may lead to lower responses of multiple hormones not only to nicotine but to a variety of stimuli, and that these alterations do not necessarily affect unstimulated circadian profiles of free cortisol.

Adrenocorticotropic Hormone↗

Feeding behavior.

Problems related to feeding behavior in horses fall into three main categories: underconsumption, overconsumption, and abnormal consumption. Anorexia may be caused by a variety of diseases and overcome by removing the underlying causes (pain, fever), and physical or chemical stimulation of appetite. "Hypophagia" may be caused by poor dentition, disease, or stress. Again, removal of the cause or stimulation by physical or chemical means may improve intakes. Acute and chronic overconsumption of feeds are reflections of the normal controls (or lack thereof) of feeding in the horse. The only reliable prevention is to limit access to feeds. Abnormal eating behaviors such as pica or coprophagy are usually caused by a dietary imbalance or boredom. Coprophagey, however, is a normal behavior in young foals. Drinking disorders are rare, the only common one being the avoidance of "strange" water. Masking water at home with specific flavors such as peppermint or vinegar may encourage the horse to drink water from other sources to which the "home" flavor has been added.

Animals↗

Promoting physical activity using an activity monitor and a tailored web-based advice: design of a randomized controlled trial [ISRCTN93896459].

BACKGROUND: Ageing is associated with a decrease in physical activity. This decrease particularly occurs during specific transitional life stages. Especially during adolescence and young adulthood a steep decrease in physical activity is observed. Inactive people are often not aware of their inactivity. Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle. METHODS: In a randomized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined. Outcome measures are level of physical activity, determinants of physical activity, quality of life, empowerment, aerobic fitness and body composition. Participants are relatively inactive adolescents and young adults who are measured at baseline, after 3 months intervention and 5 months after the end of the intervention. In addition, facilitating and hindering factors for implementation of the intervention will be investigated. DISCUSSION: The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level. It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before.

Activities of Daily Living↗

Gene 4 protein of bacteriophage T7. Purification physical properties, and stimulation of T7 DNA polymerase during the elongation of polynucleotide chains.

With the use of an in vitro complementation assay to measure activity, the gene 4 protein of bacteriophage T7 has been purified 1000-fold to yield a nearly homogeneous protein. The purified gene 4 protein is a single polypeptide having a molecular weight of 58,000. In addition to being essential for T7 DNA replication in vivo and in vitro, the gene 4 protein is required for DNA synthesis by the purified T7 DNA polymerase on duplex T7 DNA templates. In the absence of ribonucleoside 5'-triphosphates, DNA synthesis by the gene 4 protein and the T7 DNA polymerase is dependent on phosphodiester bond interruptions containing 3'-hydroxyl groups (nicks) in the duplex DNA. The reaction is specific for the T7 DNA polymerase, but any duplex DNA containing nicks can serve as template. The Km for nicks in the reaction is 3 x 10(-10) M.

Coliphages↗

Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy.

BACKGROUND: Chronic reflex sympathetic dystrophy (also called the complex regional pain syndrome) is a painful, disabling disorder for which there is no proven treatment. In observational studies, spinal cord stimulation has reduced the pain associated with the disorder. METHODS: We performed a randomized trial involving patients who had had reflex sympathetic dystrophy for at least six months. Thirty-six patients were assigned to receive treatment with spinal cord stimulation plus physical therapy, and 18 were assigned to receive physical therapy alone. The spinal cord stimulator was implanted only if a test stimulation was successful. We assessed the intensity of pain (on a visual-analogue scale from 0 cm [no pain] to 10 cm [very severe pain]), the global perceived effect (on a scale from 1 [worst ever] to 7 [best ever]), functional status, and the health-related quality of life. RESULTS: The test stimulation of the spinal cord was successful in 24 patients; the other 12 patients did not receive implanted stimulators. In an intention-to-treat analysis, the group assigned to receive spinal cord stimulation plus physical therapy had a mean reduction of 2.4 cm in the intensity of pain at six months, as compared with an increase of 0.2 cm in the group assigned to receive physical therapy alone (P<0.001 for the comparison between the two groups). In addition, the proportion of patients with a score of 6 ("much improved") for the global perceived effect was much higher in the spinal cord stimulation group than in the control group (39 percent vs. 6 percent, P=0.01). There was no clinically important improvement in functional status. The health-related quality of life improved only in the 24 patients who actually underwent implantation of a spinal cord stimulator. Six of the 24 patients had complications that required additional procedures, including removal of the device in 1 patient. CONCLUSIONS: In carefully selected patients with chronic reflex sympathetic dystrophy, electrical stimulation of the spinal cord can reduce pain and improve the health-related quality of life.

Adult↗

Alcohol-induced stimulation and sedation: relation to physical aggression.

The relation between the stimulating and the sedating effects of acute alcohol consumption on human physical aggression was examined. Sixty male social drinkers were assigned to either an alcohol or a sober group. Aggression was measured using a modified version of S. Taylor's (1967) aggression paradigm, in which electric shocks are received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the intensity and the duration of the shocks selected. Stimulation and sedation were measured using a self-report inventory. Results demonstrated that stimulation was positively related to aggression, but only in the intoxicated state. Sedation was not related to aggression in either the intoxicated or the sober state.

Adult↗

Effects of physical exercise and cold stimulation on serum testosterone level in men.

The concentrations of testosterone (TS) and other related hormones in serum were examined before and after physical exercise with a bicycle ergometer (90 Watts, 20 min.) and a cold water stimulation in 32 19-year-old males. While exercising, the serum TS level significantly increased by 20.8% (p less than 0.05), the luteinizing hormone (LH) level by 3.6% (p less than 0.05) and noradrenaline (NA) level by 140.0% (p less than 0.01). During cold water stimulation, TS decreased by 10.0%, LH increased by 22.1% and NA decreased by 23.8%. Based on changes in hormone levels within the individual during the loads. there was a significant positive correlation coefficient (r) between TS and LH, and between TS and NA, with r (TS-LH) = 0.399 (p less than 0.05) and r (TS-NA) = 0.481 (p less than 0.05) for physical exercise, while r (TS-LH) = 0.403 (p less than 0.05) and r (TS-NA) = 0.431 (p less than 0.05) for cold water stimulation, respectively. These results suggest that physical exercise increases TS level in serum by increasing LH and NA levels, but these tendencies were not found with cold water stimulation.

Adult↗

Multi-whisker stimulation and its effects on vibrissa units in rat SmI barrel cortex.

Ceramic piezoelectric 'bimorphs' were used to construct multiangular mechanical stimulators which are small enough to attach to separate, adjacent vibrissae on the mystacial face pad of rodents. Use of two stimulators to independently deflect pairs of whiskers revealed that the responses of SmI cortical vibrissa units are determined by the direction in which both hairs are moved, the spatial sequence of the displacements, and the particular combination of whiskers that are stimulated. The stimulators can thus serve as the basic elements in a large array of independently controllable whisker deflectors.

Animals↗

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes.

Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.

Analgesics↗

Effect of acute and chronic spinal transection on evoked secretion of adrenal medullary catecholamines in the cat.

Eight cats were spinally transected at T3. After an acute (0-5 days) or chronic (15-37 days) period, animals were rendered decerebrate and the effects of visceral (bladder distention) and somatic (sciatic nerve stimulation) stimuli were examined. Epinephrine, norepinephrine and dopamine levels were measured in plasma collected from the left adrenolumbar vein; heart rate and blood pressure were continuously monitored. In chronic animals both visceral and somatic stimuli most frequently evoked prominent increases in blood pressure and the secretion of adrenal medullary catecholamines; the same stimuli caused little change in these parameters in acute animals. These data indicate that a condition similar to the clinical syndrome of autonomic hyperreflexia may be elicited in the chronic spinally transected cat, and that this condition is accompanied by a notable activation of the adrenal medulla.

Acute Disease↗

Preliminary study of the motility processes in the stalked heliozoan Actinocoryne contractilis.

The marine stalked heliozoan Actinocoryne contractilis is capable of rapid contraction under the effect of mechanical or electrical stimulation. A brief analysis of this movement is discussed. During this contraction, microtubules of the axopods and of the stalk are destabilized. The heliozoan transforms into an amoeboid form and can creep onto the substrate. Microfilaments are visible at this stage. Polymerization of microtubular bundles initiates the regrowth of the head. Without calcium, or in the presence of inhibitors of Ca2+, contraction is considerably slowed down or totally inhibited.

Animals↗