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A single re-implanted ventral root exerts neurotropic effects over multiple spinal cord segments in the adult rat.

Spinal cord injuries, particularly traumatic injuries to the conus medullaris and cauda equina, are typically complex and involve multiple segmental levels. Implantation of avulsed ventral roots into the spinal cord as a repair strategy has been shown to be neuroprotective and promote axonal regeneration by spinal cord neurons into an implanted root. However, it is not well known over what distance in the spinal cord an implanted ventral root can exert its neurotropic effect. Here, we investigated whether an avulsed L6 ventral root acutely implanted into the rat spinal cord after a four level (L5-S2) unilateral ventral root avulsion injury may exert neurotropic effects on autonomic and motor neurons over multiple spinal cord segments at 6 weeks postoperatively. Using retrograde labeling techniques and stereological quantification methods, we demonstrate that autonomic and motor neurons from all four lesioned spinal cord segments, spanning more than an 8 mm rostro-caudal distance, reinnervated the one implanted root. The rostro-caudal distribution suggested a gradient of neurotropism, where the axotomized neurons closest to the implanted site had the highest probability of root reinnervation. These results suggest that implantation of a single ventral root may provide neurotropic effects to injured neurons at the site of lesion as well as in the adjacent spinal cord segments. Our findings may be of translational research interest for the development of surgical repair strategies after multi-level conus medullaris and cauda equina injuries, in which fewer ventral roots than spinal cord segments may be available for implantation.

Amidines↗

Plasma Hsp72 is higher in runners with more serious symptoms of exertional heat illness.

Exertional heat illness is a potentially fatal disorder that primarily affects fit young men. Plasma Hsp72 may be important in the aetiology of this disorder, acting as a danger signal to the organism and leading to an inflammatory response. The aim of this study was to determine whether patients with exertional heat illness following a 14 km run show a difference in their plasma Hsp72 concentration compared with control subjects who completed the event without incident. Patients (n = 22) and controls (n = 7) were all male. The patients were subdivided into two groups, one of which exhibited more serious symptoms indicating neurological impairment such as confusion (n = 13) (CNS) while the other group exhibited mild symptoms (MILD) (n = 9). The CNS group had a higher rectal temperature (T(rec)) compared with the control group (41.0 +/- 0.3 vs. 39.8 +/- 0.2 degrees C, P < 0.05, mean +/- SE). Immediately after the run plasma Hsp72 was higher in the CNS group compared to controls and patients with mild symptoms (37.9, 17.0, and 20.9 ng/ml, respectively, P < 0.005). There was a correlation between plasma Hsp72 and T(rec) measured immediately after the race (r = 0.597, P < 0.001, n = 29). However, core temperature was not the only factor leading to increased plasma Hsp72 immediately post race. Plasma Hsp72 was still higher in CNS patients compared with the control group (P < 0.05) when T(rec )was included as a covariate. In conclusion, plasma Hsp72 was elevated immediately after a 14 km run with higher levels in patients with more serious symptoms of heat illness.

Adult↗

Electromyography of superficial cervical muscles with exertion in the sagittal, coronal and oblique planes.

The purpose of the current study was twofold: (1) to determine the isometric force and electromyographic (EMG) relationship of the sternocleidomastoid, splenii and trapezii muscles bilaterally in graded and maximal exertions in the sagittal, coronal and oblique planes. and (2) to develop regression equations to predict force based on the EMG scores. A newly designed and validated cervical isometric strength testing device was used to measure the cervical muscle isometric strength and force/EMG relationship in cervical flexion, extension, bilateral lateral flexion, bilateral anterolateral flexion, and bilateral posterolateral extension, all beginning with an upright seated neutral posture. A group of 40 healthy subjects were asked to exert their cervical motions in the directions of interest, while the force output and EMG from the sternocleidomastoids, splenii, and trapezii were sampled bilaterally at 1 kHz. ANOVA, correlation, and regression analyses were carried out. The force and EMG scores were significantly different between the directions of effort (P<0.01). All regressions were significant (P<0.01). All subjects registered the highest forces in pure extension and the lowest in pure flexion, showing a gradual decrease from the posterior to anterior direction. There was a modest correlation between EMG of the investigated muscles and force (r=0.15-0.76, P<0.01). EMG output was, for example, approximately 66% higher in flexion than in extension (while force output was roughly 30% less in flexion than extension) - thus relatively more muscle activity was required in flexion than extension to generate a given force. The intermediate positions (i.e. anterolateral flexion) revealed force/EMG ratio scores that were intermediate in relation to the force/EMG ratios for pure flexion and pure extension. The cervical muscle strength and cervical muscle EMG are therefore dependent on the direction of effort.

Acceleration↗

Long-term study of high-dose diltiazem in chronic stable exertional angina.

The efficacy of a calcium slow channel-blocking drug, diltiazem (360 mg/day), was compared to placebo in 15 men with exertional angina during a 21-week study. Symptom-limited exercise testing was used to evaluate the effects of the drug. Analysis of variance indicated the increase in the values of three time-related variables, time to onset of angina, time to onset of 1 mm ST depression, and total duration of exercise, were highly significant (all p less than 0.001). The increase from the second week of placebo to the last week of diltiazem was 4 X 1 minutes for time to angina, 2 X 4 minutes for time to 1 mm ST depression, and 2 X 3 minutes for total duration. In addition, the differences between mean values of these variables for placebo and corresponding diltiazem period at weeks 3 and 4 were significant (p less than 0.01, p less than 0.01, p less than 0.05) and for diltiazem week 20 and placebo week 21 were significant (p less than 0.005, p less than 0.01, p less than 0.005). Weekly angina frequency was reduced from a mean of 17 episodes/week during placebo to one episode/week during diltiazem (p less than 0.001). Submaximal pressure-rate product was reduced significantly during diltiazem (p less than 0.001), and the ECG evidence of myocardial ischemia was reduced by diltiazem at submaximal (p less than 0.02) and maximal exercise (p less than 0.001). The drug was well tolerated and appears to be effective monotherapy for exertional angina.

Aged↗

Exertional angina pectoris caused by coronary arterial spasm: effects of various drugs.

In four patients with exertional angina induced by arm exercise, coronary arteriograms taken before, during and after the attack demonstrated that spasm appeared in the large coronary artery supplying the area of myocardium shown to be ischemic in the electrocardiogram during the attack. The spasm disappeared with subsidence of the attack after administration of nitroglycerin. Anginal attacks induced by treadmill exercise were not suppressed by propranolol, 60 mg orally, in two of the four patients. However, such attacks were suppressed in all patients by oral administration of diltiazem (90 mg, four patients) or nifedipine (20 mg, three patients) or intramuscular injection of phentolamine (0.2 mg/kg body weight, three patients). It is concluded that coronary arterial spasm can be induced by exercise and can cause exertional angina in some patients. Diltiazem and nifedipine, calcium antagonistic drugs, prevent spasm.

Adult↗

Clinical features and prognostic implications of myocardial ischemia at rest in patients with exertional angina pectoris.

The prognosis of patients with coronary artery disease (CAD) is mainly influenced by organic factors such as cardiac muscle loss and extent of CAD. The aim of this study was to investigate whether a functional factor--reversible myocardial ischemia at rest--plays an independent prognostic role. Thus, 2 groups of patients were studied and followed up for 46 +/- 32 months: 1 group (483 patients) had ischemic electrocardiographic changes only on effort and another group (224 patients) both on effort and at rest. The 2 groups did not differ significantly as to age, gender, coronary risk factors, baseline electrocardiographic abnormalities, incidence of previous myocardial infarction, angiographic left ventricular dysfunction, and extent of coronary stenoses (> or = 50% diameter reduction). There were 65 deaths (40 of which were from cardiac causes) during the 5-year follow-up. Despite the similar incidence of known predictors of prognosis, Kaplan-Meier survival analysis revealed a significantly lower 5-year survival rate in patients with mixed (84.4%) rather than exertional (92.1%) ischemia (p < 0.05 by Mantel-Haenszel test). If only cardiac causes of deaths were considered, the 5-year survival rate was still lower in patients with mixed (89.6%) rather than exertional (93.9%) ischemia. Finally, reversible ischemia at rest was an independent predictor of survival by Cox multivariate regression analysis, preceded only by the extent of CAD and left ventricular dysfunction. Thus, reversible ischemia at rest plays an independent negative role in the long-term clinical outcome of patients with CAD and positive exercise stress test results.

Aged↗

Vector representations of human strength in whole body exertion.

This paper summarises a number of studies of human strength in tasks of static whole body exertion. Measurements were made using a transducer bar which allowed the simultaneous recording of the vertical and horizontal components of any force applied to it by the subject. In each experimental condition, each subject exerted his or herself in all directions in the sagittal plane (ie, that plane which bisects an individual in the antero-posterior direction). Thirty conditions were investigated. Five heights of the bar above the ground, ranging from 1.75 m to 0.25 m, were tested. Various constraints were imposed upon the placement of the subjects' feet. In some conditions a 'ceiling' or 'wall' confined the subject. The results are presented in the form of diagrams which show the magnitude and direction of all possible force vectors in the sagittal plane.

Journal Article↗

Fermentable carbohydrates exert a more potent cholesterol-lowering effect than cholestyramine.

The purpose of this work was to assess the respective role of bile acid excretion and of the end-products of cecal fermentations in the cholesterol-lowering effect of complex carbohydrates. The effects of two different fermentable carbohydrates (guar gum, beta-cyclodextrin), and sequestrant resin (cholestyramine) have been investigated in male Wistar rats. Guar gum and beta-cyclodextrin are broken down in the large bowel, with fermentation rich in propionic acid (37% against 26% for control), whereas cholestyramine did not enhance cecal fermentation. beta-Cyclodextrin and guar gum were less potent than cholestyramine to enhance bile acids and sterol excretion. Nevertheless, fermentable carbohydrates exerted a more potent cholesterol-lowering effect than cholestyramine. beta-Cyclodextrin also depressed triacylglycerol-rich lipoprotein (TGRLP). Fermentable carbohydrates lowered cholesterol of LDL and HDL1 fractions. The induction of hepatic HMG-CoA reductase was practically proportional to rate of fecal steroid excretion. Moreover, with beta-cyclodextrin, hepatic HMG-CoA reductase induction was concomitant to a decrease in fatty acid synthase (FAS) activity. Thus, the cholesterol-lowering effect of fermentable carbohydrates could be related to a depressed lipogenesis, as well as to an accelerated removal of HDL1, in relation to an elevated hepatic demand of cholesterol. In conclusion, fermentable carbohydrates could favour cholesterol elimination and have a general lipid-lowering effect by exerting more complex physiological effects than cholestyramine.

Animals↗

Possible involvement of cholinergic and glycinergic amacrine cells in the inhibition exerted by the ON retinal channel on the OFF retinal channel.

In the frog retina, the inhibition exerted by the ON channel on the OFF channel was evidenced by the increase in transient ganglion cell OFF responses, when the ON channel was blocked by 2-amino-4-phosphonobutyrate (APB). Intraocular administration of the neurotoxic choline analog ethylcholine mustard arizidinium ion (ECMA) also provoked an increase in the number of spikes of transient ganglion cell OFF responses, without suppressing the ON responses. APB, when administrated after ECMA, abolished the ON responses, but did not modify the OFF responses already increased by ECMA. Neurons located in the inner part of the inner nuclear layer were histologically altered by the toxin, and choline acetyltransferase activity was significantly depressed in ECMA-treated retinas. A double immunostaining experiment showed that amacrine cells containing glycine bear muscarinic binding sites. These results confirm the participation of cholinergic neurons in the inhibition exerted by the ON retinal channel on the OFF retinal channel, and suggest the involvement of a cholinergic/glycinergic loop of amacrine cells in this mechanism.

Acetylcholine↗

(+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters.

The effects of the novel high affinity cannabinoid receptor agonist (+)-WIN 55,212-2 ((R)-4,5-dihydro-2-methyl-4(4-morphoinylmethyl)-1-(1-naphthalen ylcarbonyl)-6H-pyrrolo[3,2,1-ij]quinolin-6-one) on severity of dystonia were investigated in mutant Syrian hamsters with primary generalized dystonia. Following injections of (+)-WIN 55,212-2 (1.0-5.0 mg/kg i.p.) a dose-dependent reduction of the severity of dystonia was observed. At antidystonic doses (2.5 and 5.0 mg/kg i.p.) (+)-WIN 55,212-2 caused a reduction of spontaneous motor activity and catalepsy. 1 mg/kg of (+)-WIN 55,212-2 exhibited neither antidystonic effects nor any side effects. However, the coadministration of 1.0 mg/kg (+)-WIN 55,212-2 with an ineffective dose of diazepam (0.1 mg/kg i.p.) exerted antidystonic effects in the absence of severe side effects. Although psychotropic effects of cannabinoids, such as (+)-WIN 55,212-2, limit the therapeutical utility of cannabinoids, the present data indicate that cannabinoids exert antidystonic effects and that low doses of cannabinoids may increase antidystonic efficacy of benzodiazepines.

Analgesics↗

Does dopamine exert a tonic inhibitory control on the release of striatal acetylcholine in vivo?

The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D2 receptors with (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dopamine D1 receptors with 0.5 mg/kg SCH 39166 or 0.1 mg/kg SCH 23390, or by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH 39166, SCH 23390 or reserpine + alpha-methyltyrosine reduced acetylcholine release by about a maximum of 30%. Stimulation of dopamine D2 receptors with LY 171555 (quinpirole) at a low, sedative dose (0.05 mg/kg) reduced acetylcholine release by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover, LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg)- or SKF 38393 (20 mg/kg)-pretreated rats did not decrease acetylcholine release, suggesting that its effect is through a dopamine D1 receptor-mediated mechanism. In contrast, in dopamine-depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment (about 80%), thus acting independently of dopamine D1 receptor mechanisms. These results indicate that, in normal circumstances, endogenous dopamine facilitates striatal acetylcholine release through dopamine D1 receptors. The results argue against the commonly accepted view that dopamine D2 receptors exert a tonic inhibitory control on acetylcholine release. Moreover, they suggest that dopamine D2 receptors, in circumstances of dopamine depletion, may exert an inhibitory control on acetylcholine release independent of dopamine D1 receptor mechanisms.

Acetylcholine↗

Changes in estrogen receptors in the mediobasal hypothalamus mediate the facilitory effects exerted by the male's olfactory cues and progesterone on feminine behavior in the male rat.

The purpose of this study was to determine whether facilitory effects exerted by olfactory cues on lordosis behavior in the male rat involved changes in estradiol receptors at the hypothalamic level. Male rats were orchidectomized as adults. They were given either 25 micrograms estradiol benzoate (EB) alone or 25 micrograms EB and 100 micrograms progesterone (P) sequentially and exposed or not to the odor of male urine. Some of them were tested for lordosis behavior at 8 h after P. The other ones were killed 4 h after P and used for estradiol (E2) and P receptor assay in mediobasal hypothalamus (MBH). Olfactory cues were shown to increase the number of E2 receptors in both the animals given EB or EB + P. Progesterone as such appeared to be capable of increasing the number and the rate of occupancy of E2 receptors. A population of constitutive and estrogen-inducible P receptors was detected in the MBH. Since only the animals given EB + P were shown to be sensible to the facilitory effects of male urine on lordosis behavior, it may be assumed that E2 and P on one hand and olfactory cues on the other exert cumulative effects at the level of the MBH and that both a high level and a high rate of occupancy of E2 receptors are necessary for the olfactory cues to facilitate the display of lordosis behavior in the male rat.

Animals↗

The effects of lithium in vitro and ex vivo on adenylate cyclase in brain are exerted by distinct mechanisms.

The effects of lithium on basal and forskolin-stimulated activity of adenylate cyclase in membrane preparations from cerebral cortex of the rat have been studied. Chronic treatment with lithium, yielding a level of lithium in serum of 0.71 +/- 0.18 mmol/l, reduced forskolin-stimulated activity in total homogenates but exerted no effect on the basal activity. Lithium in vitro, at 2 and 10 mM, did not influence the basal enzyme activity in membranes from either control or lithium-treated animals. The sensitivity of forskolin-stimulated adenylate cyclase to lithium in vitro was unaltered after chronic treatment and the in vitro and ex vivo effects of lithium on this parameter were additive. The inhibitory ex vivo effect of lithium was not antagonized by increasing concentrations of magnesium and the inhibitory effect of lithium ex vivo was still persistent after washing of the membranes. The present results indicate that lithium exerts its ex vivo effect on the activated cyclase, independently of the in vitro effect. Both effects may, however, contribute to the in vivo effect of lithium during chronic treatment.

Adenylyl Cyclases↗

Studies on the distribution of abnormal cells in cytologic preparations. VI. Pressure exerted by the gynecologist during smearing.

A model system consisting of exfoliated abnormal cells and acellular viscous, mucus-like material was used to investigate the effect of the pressure exerted during smearing on the number of abnormal cells present in the preparations. Smears were made with a cotton swab applicator from left to right with parallel strokes, without overlapping smearing and without rotating the instrument of cell collection. Light and heavy pressures done during smearing procedure were recorded by the aid of an automatic scale. By means of the smearing technique, a gradual decrease in the total number of cells was recorded along the pathway of smearing. By using heavy pressure, however, cell accumulation also occurred at the end of the pathway of the last smearing strokes. Smears made with heavy pressure contained 13% more tumor cells than those made with light pressure. It is concluded that the pressure exerted by the operator during smearing may be an important parameter influencing both the number and the distribution of abnormal cells on smear preparations. These considerations may be of significance in screening programs for tumor cell detection.

Animals↗

Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris.

The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23-28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial. Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy. The mean (+/- SEM) exercise time to the development of angina on treadmill walking increased from 6.9 +/- 0.4 min on placebo to 9.4 +/- 0.5 min on KB-944 100 mg/day (P less than 0.001) and 9.7 +/- 0.8 min on KB-944 200 mg/day (P less than 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 +/- 0.4 min on placebo increased to 6.5 +/- 0.5 and 6.6 +/- 0.5 min on KB-944 100 and 200 mg/day, respectively (P less than 0.01 vs placebo). The heart rate at rest of 77 +/- 3 beats/min on placebo was reduced to 68 +/- 3 beats/min on KB-944 100 mg/day (P less than 0.001) and 71 +/- 2 beats/min on KB-944 200 mg/day (P less than 0.01). The maximal heart rate and the rate-pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.

Adult↗

Exertional myocardial ischemia in diabetes: a quantitative analysis of anginal perceptual threshold and the influence of autonomic function.

Patients with diabetes are prone to silent myocardial infarction and silent exertional ischemia. Although the mechanism is not clear, it may reflect a specific impairment of the sensory innervation of the heart. To test this hypothesis, anginal perceptual threshold was measured in 32 diabetic patients and 36 nondiabetic control patients, all of whom had typical exertional angina. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of chest pain during treadmill stress electrocardiography. Although ST depression occurred earlier in the diabetic than in the nondiabetic group (111 +/- 82 versus 216 +/- 162 s, p less than 0.005), the anginal perceptual threshold in the diabetic group was delayed by a mean of 86 s (149 +/- 76 versus 63 +/- 59 s, p less than 0.001), with 95% confidence intervals of 53 to 119 s. Autonomic function tests were abnormal in the diabetic group, and in both groups regression analyses (using a third order polynomial) showed marked prolongations of anginal perceptual threshold as the heart rate responses to the Valsalva maneuver decreased to below the normal range (r = 0.5, p less than 0.001). There was a similar though less pronounced relation between anginal perceptual threshold and the heart rate responses to deep breathing (r = 0.3, p less than 0.02). These data suggest that prolongation of the anginal perceptual threshold may be caused by autonomic neuropathy involving the sensory innervation of the heart. To test sensory function, median nerve conduction studies were performed in 19 patients (10 diabetic and 9 nondiabetic).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Comparison of work rates, energy expenditure, and perceived exertion during a 1-h vacuuming task with a backpack vacuum cleaner and an upright vacuum cleaner.

The purpose of this study was to evaluate two types of industrial vacuum cleaners, in terms of cleaning rates, energy expenditure, and perceived exertion. Twelve industrial cleaners (six males and six females, age 28-39 yr) performed two 1-h vacuuming tasks with an upright vacuum cleaner (UVC) and a backpack vacuum cleaner (BPVC). Measures for oxygen uptake (VO2) and ratings of perceived exertion (RPE) were collected continuously during the 1-h vacuuming tasks. Cleaning rates for the UVC and BPVC were 7.23 and 14.98 m2min(-1), respectively. On a separate day subjects performed a maximal treadmill exercise test to determine their maximal aerobic capacity (peak VO2). Average absolute energy costs (in Metabolic equivalents), relative energy costs of the vacuum task compared to the subjects' maximal aerobic capacity (% peak VO2), and RPE responses for the 1-h vacuuming tasks were similar between vacuum cleaners, but % peak VO2 and RPE values differed between genders. These results indicate that the BPVC was more efficient than the UVC. With the BPVC, experienced workers vacuumed at a cleaning rate 2.07 times greater than the UVC and had similar levels of energy expenditure and perceived effort, compared to the slower cleaning rate with the UVC.

Adult↗

Calibrating Borg scale ratings of hand force exertion.

A study was conducted to assess the efficacy of calibrating subjective worker ratings of hand exertions to reduce error in estimates of applied force. Twenty volunteer subjects applied pinch and power grip forces corresponding to their perceptions of different Borg CR-10 scale levels using both "grip-to-scale" and "guided-grip" procedures. These data were used separately to define relationships between scale ratings and actual force application. Two gripping tasks were performed and corresponding subjective hand force ratings were calibrated using the grip-to-scale calibration data. Results showed that the mean estimation error for a 44.5 N (10 lb) power grip task was significantly reduced from 142.8 (+/-69.0) to 62.3 (+/-58.3) N. The guided-grip calibration method also significantly reduced rating error for the power grip task, however the estimates were biased toward zero. Neither calibration procedure improved rating accuracy of an 8.9 N (2 lb) pinch grip task. The study results indicate that calibration of hand force ratings using the grip-to-scale procedure may improve the accuracy of hand exertion measurements using the Borg CR-10 scale.

Adult↗