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Ventilatory control during exercise with peripheral chemoreceptor stimulation: hypoxia vs. domperidone.

Hypoxia potentiates the ventilatory response to exercise, eliciting a greater decrease in arterial PCO2 (PaCO2) from rest to exercise than in normoxia. The mechanism of this hypoxia-exercise interaction requires intact carotid chemoreceptors. To determine whether carotid chemoreceptor stimulation alone is sufficient to elicit the mechanism without whole body hypoxia, ventilatory responses to treadmill exercise were compared in goats during hyperoxic control conditions, moderate hypoxia (PaO2 = 38-44 Torr), and peripheral chemoreceptor stimulation with the peripheral dopamine D2-receptor antagonist, domperidone (Dom; 0.5 mg/kg iv). Measurements with Dom were made in both hyperoxia (Dom) and hypoxia (Dom/hypoxia). Finally, ventilatory responses to inspired CO2 at rest were compared in each experimental condition because enhanced CO2 chemoreception might be expected to blunt the PaCO2 decrease during exercise. At rest, PaCO2 decreased from control with Dom (-5.0 +/- 0.9 Torr), hypoxia (-4.1 +/- 0.5 Torr), and Dom/hypoxia (-11.1 +/- 1.2 Torr). The PaCO2 decrease from rest to exercise was not significantly different between control (-1.7 +/- 0.6 Torr) and Dom (-1.4 +/- 0.8 Torr) but was significantly greater in hypoxia (-4.3 +/- 0.7 Torr) and Dom/hypoxia (-3.5 +/- 0.9 Torr). The slope of the ventilation vs. CO2 production relationship in exercise increased with Dom (16%), hypoxia (18%), and Dom/hypoxia (68%). Ventilatory responses to inspired CO2 at rest increased from control to Dom (236%) and Dom/hypoxia (295%) and increased in four of five goats in hypoxia (mean 317%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dopamine receptors on intact anterior pituitary cells in culture: functional association with the inhibition of prolactin and thyrotropin.

Dopamine (DA) and the dopaminergic agonists bromocriptine and apomorphine inhibit the secretion of TSH as well as that of PRL by rat anterior pituitary (AP) cells in monolayer culture. The order of potency of the drugs is the same for the inhibition of both hormones: bromocriptine ED50 = 0.006 nM against PRL and 0.017 nM against TSH; apomorphine ED50 = 2.9 and 4.8 nM, respectively, and DA, ED50 = 30 and 370 nM, respectively. The dopaminergic antagonists domperidone (DOM) and metoclopramide prevent the inhibition of TSH and PRL by 10(-6) M DA (IC50 = 0.012 and 0.32 nM for metoclopramide against PRL and TSH, respectively; similarly, IC50 = 0.01 and 0.61 nM for DOM). The action of butaclamol is shown to be stereospecific, in that the (+) isomer is 1000-fold more potent in reversing the inhibition of both TSH and PRL by 10(-6) M DA than the (-) isomer [IC50 = 1.1 and 7200 nM for the (+) and (-) isomers against PRL; similarly, 6.3 and 2600 nM against TSH]. The use of radioligand-binding techniques with tritiated DOM ([3H]DOM) and dihydroergocriptine ([3H]DHE) has demonstrated a high affinity dopaminergic binding site upon rat AP cells under the same conditions as the cell cultures used in the hormone secretion studies. Both ligands have been shown to label a site with high affinity (Kd = 1-2 nM) and low capacity (2-3 fmol/10(5) cells). At this site, dopaminergic agonists and antagonists compete with both radioligands and display a rank order of potency which is the same as that shown against TSH and PRL secretion and which is typically dopaminergic. For [3H]DHE: bromocriptine Ki (0.04 nM) greater than metoclopramide = DOM (0.07 nM) greater than (+)butaclamol (0.7 nM) greater than apomorphine (20 nM) greater than DA (700 nM) greater than (-)butaclamol (2000 nM). Similar data were derived using [3H]DOM. The high affinity site is saturable, has rapid association and dissociation rates, as determined for both radioligands used, and is temperature dependent. In contrast, both radioligands bind to a second binding site on the cells that is of lower affinity (Kd = 244 nM for [3H]DOM and 678 nM for [3H]DHE) and larger capacity (100 fmol/10(5) cells for both ligands). This second site is neither stereospecific nor, using the methodology presented here, does it discriminate between other dopaminergic compounds. It is thus not considered to represent specific DA receptor binding. It is concluded that the dopaminergic stimulus causing the inhibition of TSH and PRL secretion from rat AP cells in culture is mediated via a high affinity DA receptor present upon lactotrophs and thyrotrophs and that this receptor has similar characteristics on the two cell types.

Animals↗

Treatment and prevention of delayed onset muscle soreness.

Eccentric exercise continues to receive attention as a productive means of exercise. Coupled with this has been the heightened study of the damage that occurs in early stages of exposure to eccentric exercise. This is commonly referred to as delayed onset muscle soreness (DOMS). To date, a sound and consistent treatment for DOMS has not been established. Although multiple practices exist for the treatment of DOMS, few have scientific support. Suggested treatments for DOMS are numerous and include pharmaceuticals, herbal remedies, stretching, massage, nutritional supplements, and many more. DOMS is particularly prevalent in resistance training; hence, this article may be of particular interest to the coach, trainer, or physical therapist to aid in selection of efficient treatments. First, we briefly review eccentric exercise and its characteristics and then proceed to a scientific and systematic overview and evaluation of treatments for DOMS. We have classified treatments into 3 sections, namely, pharmacological, conventional rehabilitation approaches, and a third section that collectively evaluates multiple additional practiced treatments. Literature that addresses most directly the question regarding the effectiveness of a particular treatment has been selected. The reader will note that selected treatments such as anti-inflammatory drugs and antioxidants appear to have a potential in the treatment of DOMS. Other conventional approaches, such as massage, ultrasound, and stretching appear less promising.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of dissolved organic matter source on acute copper toxicity to Daphnia magna.

The protective effect of dissolved organic matter (DOM) on metal toxicity to aquatic organisms has been reported by numerous authors. Bioavailability models such as the biotic ligand model (BLM) thus account for this factor to predict metal toxicity to aquatic organisms. Until now, however, few attempts have been made to assess the effect of the DOM source on metal speciation and toxicity and, accordingly, on BLM predictions. The aims of this study were to investigate to what extent DOMs differ in their ability to decrease acute copper toxicity to the cladoceran Daphnia magna and to evaluate if ultraviolet (UV) absorbance measurements may be a simple and effective method to incorporate DOM variability into the acute Cu-BLM for D. magna. Acute toxicity tests were carried out in artificial test water enriched with DOMs isolated from six locations in Europe and North America and in seven natural European surface waters. The acute Cu-BLM for D. magna was then used to estimate the copper complexing capacity of each DOM (expressed as % active fulvic acid, %AFA). A factor of 6 difference was observed between the lowest and the highest copper complexing capacity. A significant linear relationship was observed between the UV-absorbance coefficient at 350 nm (epsilon350) and the %AFA. Linking this relationship to the acute Cu-BLM resulted in a significant improvement of the predictive capacity of this BLM. Without accounting for this relationship, 90% of the predicted 48-h 50% effective concentrations (EC50) were within a factor of 2 of the observed EC50s; taking this relationship into account, 90% of the EC50s were predicted with an error of less than factor 1.3. The present study and other studies seem to indicate that UV absorbance may be a good measure of biologically and toxicologically relevant differences in copper binding behavior of DOM.

Animals↗

Molecular simulation of a model of dissolved organic matter.

A series of atomistic simulations was performed to assess the ability of the Schulten dissolved organic matter (DOM) molecule, a well-established model humic molecule, to reproduce the physical and chemical behavior of natural humic substances. The unhydrated DOM molecule had a bulk density value appropriate to humic matter, but its Hildebrand solubility parameter was lower than the range of current experimental estimates. Under hydrated conditions, the DOM molecule went through conformational adjustments that resulted in disruption of intramolecular hydrogen bonds (H-bonds), although few water molecules penetrated the organic interior. The radius of gyration of the hydrated DOM molecule was similar to those measured for aquatic humic substances. To simulate humic materials under aqueous conditions with varying pH levels, carboxyl groups were deprotonated, and hydrated Na+ or Ca2+ were added to balance the resulting negative charge. Because of intrusion of the cation hydrates, the model metal-humic structures were more porous, had greater solvent-accessible surface areas, and formed more H-bonds with water than the protonated, hydrated DOM molecule. Relative to Na+, Ca2+ was both more strongly bound to carboxylate groups and more fully hydrated. This difference was attributed to the higher charge of the divalent cation. The Ca-DOM hydrate, however, featured fewer H-bonds than the Na-DOM hydrate, perhaps because of the reduced orientational freedom of organic moieties and water molecules imposed by Ca2+. The present work is, to our knowledge, the first rigorous computational exploration regarding the behavior of a model humic molecule under a range of physical conditions typical of soil and water systems.

Hydrogen Bonding↗

Influence of decomposition on chemical properties of plant- and manure-derived dissolved organic matter and sorption to goethite.

Sorption of dissolved organic matter (DOM) plays an important role in maintaining the fertility and quality of soils in agricultural ecosystems. Few studies have examined the effects of decomposition on DOM sorption and chemical characteristics. This study investigated the sorption to goethite (alpha-FeOOH) of fresh and decomposed hydrophilic (HPL) and hydrophobic (HPB) DOM fractions extracted from the shoots and roots of crimson clover (Trifolium incarnatum L.), corn (Zea mays L.), soybean [Glycine max (L.) Merr.], hairy vetch (Vicia villosa L.), and dairy and poultry manures. Sorption was positively related to apparent molecular weight (MWAP), aromaticity as measured by absorptivity at 280 nm, and phenolic acid content. A 10-d laboratory microbial decomposition of the source organic matter generally increased the sorption of the extracted DOM onto goethite. The decomposition effect on sorption was greater for the HPL fractions than for the HPB fractions. There was a decrease in the MWAP values of the DOM samples following sorption to goethite. In many cases the reduction in MWAP was large, indicating a strong preference by goethite for the higher MWAP DOM fractions. The results of this laboratory-based research demonstrate that microbial processes affect the chemical characteristics of DOM which may affect the distribution of soil organic C pools.

Acids↗

Glutamate Release from Chick Retina Explants in Response to Domoic Acid.

Release of endogenous glutamate (GLU) evoked by an exogenous excitotoxin such as kainate can contribute to central nervous system (CNS) excitotoxicity. In this study, the possibility that this mechanism accounts for reported domoic acid (DOM) toxicity was investigated using the isolated chick retina. Exposing retinas to 0-100 µM DOM for 40 min caused an increased efflux of lactate dehydrogenase (LDH) and a dose-related release of GLU into the incubation medium. Neuronal damage following exposure to DOM was confirmed by histologic examination of the retina. DOM-induced GLU release occurred at 27 and 37 degrees C and was more pronounced in medium containing a low calcium concentration (0.1 mM). In contrast, K(+) evoked GLU release occurred only at 37 degrees C in 2 mM calcium, but not at 27 degrees C. DOM-induced GLU release was reduced in hyperosmolar medium (medium 1 100 mM sucrose). Similar to GLU release, the LDH release occurred at both 27 and 37 degrees C and was reduced in hyperosmolar medium. These results suggest that an increase in membrane permeability secondary to osmotic swelling and lysis rather than a calcium-dependent vesicular exocytosis mechanism is responsible for GLU and LDH release. GYKI 52466, a selective noncompetitive antagonist of the non-NMDA receptor, prevented neuronal degeneration and GLU/LDH release. MK-801, a highly potent noncompetitive NMDA receptor blocker, reduced neuronal injury (33% decrease in LDH release), but did not reduce DOM-evoked GLU release significantly. Typical excitotoxic lesions were produced at all concentrations tested, with amacrine cells in the inner nuclear layer being the most severely affected. Released GLU contributed to further excitotoxic injury, exacerbating the neurotoxic action of DOM in isolated embryonic chick retina.

Journal Article↗

[Cadmium adsorption in soil influenced by dissolved organic matter derived from rice straw and sediment].

Dissolved organic matter (DOM) is an active component in territorial ecosystems. Effects of two types of DOMs extracted from sediment(DOMsed) and rice straw(DOMrs) on isotherm adsorption of Cd in latosol red soil (acidic soil), paddy soil and drab soil(alkaline soil) were studied using batch equilibrium studies. The maximum adsorption of Cd in all the 3 soils used was reduced by the additions of both of DOMsed and DOMrs. The range of the maximum adsorption of Cd decreased from 17.3% to 93.9% from all the 3 soils when DOMs were added. It was found that the decreased in the maximum adsorption of Cd was in order of latosol red soil > paddy soil > drab soil when the same DOM(DOMsed or DOMrs) was added. Effects of DOMsed or DOMrs on Cd adsorption were positively related with the soil pH. The maximum adsorption of Cd in the soils was dependent on the characteristics of soil solid when no DOM was added, and decided by the DOMs in soil solution when DOM was added. The results imply that the proposed technology using organic manure to stabilize Cd in soils is not suitable for remediation of contaminated soil.

Absorption↗

[Three-dimensional excitation emission matrix fluorescence spectroscopic characterization of dissolved organic matter].

Three-dimensional excitation emission matrix fluorescence spectroscopy (3DEEM) was applied to characterize the fluorescence properties of dissolved organic matter (DOM) in lakes, rivers, streams, and ground waters. The results showed that the 3DEEM of DOM in aquatic environments mainly have four fluorescence peaks: peak A and C was referred to as fulvic-like fluorescence, and peak B and D was referred to as protein-like fluorescence. Results of river water DOM typically showed strong fulvic-like fluorescence. Polluted river waters often showed strong protein-like fluorescence. Four peaks were also found in the 3DEEM of lake DOM, which can origin from terrestrial runoff or from sources within the lakes. In Lake Baihua, strong protein-like fluorescence was found owing to the pollution by municipal wastewaters. Groundwater DOM has relatively lower DOC concentrations at 0.56-0.85 mg x L(-1) and is characterized by fulvic-like fluorescence only if it was polluted by municipal wastewaters, and then it has strong protein-like fluorescence. The authors demonstrate that for all DOM samples, fluorescence intensity at peak C and absorption at 254 nm both showed a strong correlation with DOC concentrations (r2 = 0.82 and 0.95, respectively). Also a strong linear correlation between UV-fulvic-like fluorescence and visible fulvic-like fluorescence was found (r2 = 0.96). The fulvic-like fluorescence at peak A and C varied in accordance to each other with the pH of the DOM samples, and the maximum fluorescence occurred at pH 10, while the maximum value of protein-like fluorescence (peak B) occurred at pH around 8.5.

English Abstract↗

Various treatment techniques on signs and symptoms of delayed onset muscle soreness.

Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between treatments. Therefore, we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS. In fact, the NSAID and A. montana treatments appeared to impede recovery of muscle function.

Journal Article↗

[Effects of dissolved organic matter on napropamide adsorption and transport in soil system].

Dissolved organic matter (DOM) can affect the environmental behaviors of herbicides in soil. Batch adsorption and column experiments were conducted to measure the sorption and leaching of napropamide in soils in the presence of DOM derived from green manure (GM) and sewage sludge (SS). DOM reduced sorption of napropamide significantly onto the tested soils, consequently which facilitated the transport of napropamide exhibited by soil column experiment. The sorption inhibition and the increased mobility of napropamide caused by DOM of GM origin were more significant than that of SS origin for the same soil. Within the selected concentration range of the napropamide and DOM in this study napropamide sorption isotherm could be described well by the Freundlich equation. In comparison with the control, DOM of GM and SS origins could reduce napropamide adsorption by 22.9% and 11.3% in the yellow-brown soil and 9.5% and 6.5% in the calcareous soil, respectively. Correspondingly, in the presence of DOM the leaching losses of napropamide in soil column increased by 73.42% and 26.87% in the yellow-brown soil and 43.54% and 28.29% in the calcareous soil, respectively.

Adsorption↗

Mechanisms of exercise-induced delayed onset muscular soreness: a brief review.

Delayed-onset muscular soreness (DOMS), the sensation of pain and stiffness in the muscles that occurs from 1 to 5 d following unaccustomed exercise, can adversely affect muscular performance, both from voluntary reduction of effort and from inherent loss of capacity of the muscles to produce force. This reduction in performance is temporary; permanent impairment does not occur. A number of clinical correlates are associated with DOMS, including elevations in plasma enzymes, myoglobinemia, and abnormal muscle histology and ultrastructure; exertional rhabdomyolysis appears to be the extreme form of DOMS. Presently, the best treatment for DOMS appears to be muscular activity, although the sensation again returns following the exercise. Training for the specific contractile activity that causes DOMS reduces the soreness response. The etiology and cellular mechanisms of DOMS are not known, but a number of hypotheses exist to explain the phenomenon. The following model may be proposed: 1) high tensions (particularly those associated with eccentric exercise) in the contractile/elastic system of the muscle result in structural damage; 2) cell membrane damage leads to disruption of Ca++ homeostasis in the injured fibers, resulting in necrosis that peaks about 2 d post-exercise; and 3) products of macrophage activity and intracellular contents accumulate in the interstitium, which in turn stimulate free nerve endings of group-IV sensory neurons in the muscles leading to the sensation of DOMS.

Animals↗

Dissolved organic matter status in Damietta estuary of the Nile.

The seasonal distribution of dissolved organic matter (DOM) in Damietta estuary of the Nile was investigated to show the influence of organic pollution. The DOM values increased generally with depth. The vertical values of DOM varied from 0.23-9.97 mg O/l. The average DOM values gave noticeable local variations in each month and pronounced monthly variations at each station. The maximum monthly average value in August coincided principally with elevation of temperature and the minimum in December is due mainly to the drop in temperature. The direct effect of pollution, in increasing the DOM content in the estuary, decreases relatively towards the sea, as indicated by the minimum regional average DOM value at the mouth of Damietta estuary. An inverse relationship was found generally between the averages of DOM and those of dissolved oxygen.

Egypt↗

Effects of systemic and intracerebroventricular domperidone treatment on striatal and hypothalamic dopaminergic neurons.

In this study we compared the effects of systemic administration of haloperidol (HAL), a typical dopaminergic antagonist and of domperidone (DOM), a dopamine (DA) receptor blocker which does not cross the blood brain barrier but has a potency similar to HAL at DA receptors, on hypothalamic and striatal DA system turnover (evaluated by means of HVA and DOPAC levels) and prolactin (PRL) secretion in male rats. In accordance with previous data, we found that HAL (1 mg/kg, i.p.) raised DOPAC and HVA levels whereas DOM (1 mg/kg, i.p.) did not alter DA turnover in striatum. Both DOM and HAL affected the hypothalamic DA system, increasing DOPAC levels in a pattern similar to that observed in PRL secretion. An intracerebroventricular (icv) injection of DOM and HAL (4 micrograms/10 microliters/rat) was then made to investigate its effect on DA turnover in this experimental condition at striatal and hypothalamic level. DOM stimulated DA turnover a little in the striatum though its action was delayed; no effects were seen on HVA and DOPAC concentrations in the hypothalamus at any of the tested times. On the other hand, an equal amount of HAL induced an increase in striatal HVA and DOPAC levels, with no significant effects on hypothalamic DA metabolites. These results show that systematically administered DOM and HAL may affect the hypothalamic tuberoinfundibular DA system, probably acting through PRL release. Furthermore DOM, even when injected icv, shows only weak antidopaminergic action on DA turnover in both central areas.

3,4-Dihydroxyphenylacetic Acid↗

Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.

We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT(2)) receptor (5-HT(2)R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT(2A)R antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT(2A/C)R antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT(2B/C)R antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), and several 5-HT(2)R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT(2)R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT(2A)R antagonist R93274 as well as the non-selective 5-HT(2A)R antagonists (R99647, ketanserin, risperidone, pipamperone and mianserin) significantly inhibited tryptamine-induced forepaw treading and tremors, and reversed peripherally mediated cyanosis into hyperaemia; only the 5-HT(2A/C)R antagonists R99647 and mianserin inhibited the tryptamine-induced hunched back. Intermittent DOM administration (intravenously every 48 h for 12 days) did not change the centrally mediated tryptamine-induced forepaw treading, tremors and hunched back at 1, 4 or 7 days after the last DOM pretreatment. The DOM-induced head twitch response, measured immediately after every DOM injection, was not affected. In contrast, peripherally mediated cyanosis was reversed into hyperaemia in 75, 11 and 20% of all pretreated rats at 1, 4 and 7 days, respectively, after the last DOM administration. Taken together, these finding suggest that central 5-HT(2A)Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs mediate tryptamine-induced cyanosis, and that 5-HT(2A)Rs mediate tryptamine-induced hunched back. Peripheral 5-HT(2C)Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT(2A)Rs.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Possible involvement of serotonin receptors in the facilitatory effect of a hallucinogenic phenethylamine on single facial motoneurons.

2,5-Dimethoxy-4-methylamphetamine (DOM, "STP") is a potent hallucinogen, proposed to be a serotonin receptor agonist. Its effects have not previously been tested upon central neurons where serotonin is excitatory and serotonin antagonists are effective. Extracellular single unit recordings were obtained from facial motoneurons in anaesthetized rats, and drugs were applied from five-barrelled micropipettes by iontophoresis. Facial motoneurons were commonly silent. During subthreshold application of glutamate, firing could be induced by dopamine and DOM. As reported by others, serotonin and noradrenaline also excited facial motoneurons under these conditions. Methysergide antagonized responses to serotonin and DOM but not those to noradrenaline; methysergide could not usually discriminate between responses to serotonin and dopamine. Ketanserin reversibly antagonized (but could not discriminate between) responses to serotonin, dopamine, and noradrenaline. Chlorpromazine antagonized responses to dopamine at doses that did not alter serotonin-induced excitation, and responses to DOM were not reduced by doses of chlorpromazine, that had no local anaesthetic effect on action potentials elicited by DOM and serotonin. These results suggest that DOM is an agonist on at least one type of central serotonin receptor. This receptor may also be a ketanserin (5-HT2) binding site.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Hyperbaric oxygen therapy for delayed onset muscle soreness and closed soft tissue injury.

BACKGROUND: Soft tissue injuries (including muscle damage after unaccustomed exercise) are common and are often associated with athletic activity. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere. OBJECTIVES: To assess the benefits and harms of HBOT for treating soft tissue injury, including delayed onset muscle soreness (DOMS). SEARCH STRATEGY: We searched the following in July 2004: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM and reference lists from relevant articles. Relevant journals were handsearched and researchers in the field contacted. SELECTION CRITERIA: Randomised trials comparing the effect on closed soft tissue injury (including DOMS) of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Four reviewers independently evaluated study quality and extracted data. Most of the data presented in the review were extracted from graphs in the trial reports. MAIN RESULTS: Nine small trials involving 219 participants were included. Two trials compared HBOT versus sham therapy on acute closed soft tissue injuries (ankle sprain and medial collateral knee ligament injury respectively). The other seven trials examined the effect of HBOT on DOMS following eccentric exercise in unconditioned volunteers. All 32 participants of the ankle sprain trial returned to their normal activities. There were no significant differences between the two groups in time to recovery, functional outcomes, pain, or swelling. There was no difference between the two groups in knee function scores in the second acute injury trial; however, intention-to-treat analysis was not possible for this trial. Pooling of data from the seven DOMS trials showed significantly and consistently higher pain at 48 and 72 hours in the HBOT group (mean difference in pain score at 48 hours [0 to 10 worst pain] 0.88, 95% CI 0.09 to 1.67, P = 0.03) in trials where HBOT was started immediately. There were no differences between the two groups in longer-term pain scores or in any measures of swelling or muscle strength. No trial reported complications of HBOT but careful selection of participants was evident in most trials. AUTHORS' CONCLUSIONS: There was insufficient evidence from comparisons tested within randomised controlled trials to establish the effects of HBOT on ankle sprain or acute knee ligament injury, or on experimentally induced DOMS. There was some evidence that HBOT may increase interim pain in DOMS. Any future use of HBOT for these injuries would need to have been preceded by carefully conducted randomised controlled trials which have demonstrated effectiveness.

Athletic Injuries↗

Abnormal microenvironmental signals underlie intestinal aganglionosis in Dominant megacolon mutant mice.

Dominant megacolon (Dom) is a mutation in an uncharacterized murine gene which is associated with intestinal aganglionosis and the focal absence of melanocytes in heterozygous animals. The phenotype of Dom/+ heterozygotes is similar to the lethal spotted and piebald lethal mutations, which are due to defects in endothelin-mediated intercellular signals. In this study, the DbetaH-nlacZ transgenic marker for enteric neural crest cells is used to study the distribution of enteric neurons and their precursors in Dom/+ mice and embryos. Vagal neural crest-derived cells in wild-type embryos colonize the gut in a cranial-to-caudal progression. In Dom/+ embryos, colonization was retarded from the earliest stages examined (embryonic Day 11.0), including progression through the small intestine. The early onset of this defect contrasts with impaired neural crest colonization associated with the lethal spotted and piebald lethal mutations which manifest only in the large intestine. Analysis of Dom/+ - +/+ aggregation chimeras indicated that defective colonization is not an autonomous (intrinsic) property of Dom/+ neuroblasts, but like lethal spotted and piebald lethal, the Dominant megacolon mutation directly or indirectly affects microenvironmental signals which influence the migration, proliferation, and/or survival of enteric neural crest cells.

Animals↗