The effect of flumazenil on CNS oxygen toxicity in the rat

The effect of afferent cutaneous electrical stimulation on the spasticity of leg muscles was studied in 20 patients with chronic hemiplegia after stroke. Stimulation electrodes were placed over the sural nerve of the affected limb. The standard method of cutaneous stimulation, TENS with impulse frequency of 100 Hz, was applied. The tonus of the leg muscles was measured by means of an electrohydraulic measuring brace. The EMG stretch reflex activity of the tibialis anterior and triceps surae muscles was detected by surface electrodes and recorded simultaneously with the measured biomechanical parameters. In 18 out of 20 patients, a mild but statistically significant decrease in resistive torques at all frequencies of passive ankle movements was recorded following 20 min of TENS application. The decrease in resistive torque was often (but not always) accompanied by a decrease in reflex EMG activity. This effect of TENS persisted up to 45 min after the end of TENS. The results of the study support the hypothesis that TENS applied to the sural nerve may induce short-term post-stimulation inhibitory effects on the abnormally enhanced stretch reflex activity in spasticity of cerebral origin.     

Caffeine attenuates vasovagal reactions in female first-time blood donors.

The experience of vasovagal reactions during blood donation (e.g., faintness, dizziness, lightheadedness) can be a deterrent to repeat donation. Because these reactions are associated with decreases in blood pressure, caffeine was examined as a potential modulator of vasovagal reactions by virtue of its pressor effects. Using a randomized, double-blind design, 62 female undergraduate 1st-time blood donors received either 0, 125, or 250 mg of caffeine prior to blood donation. Participants who received 250 mg of caffeine had lower scores on the Blood Donation Reactions Inventory, required fewer interventions by phlebotomists for negative reactions, and reported a greater likelihood of repeat donation than participants who received placebo. These findings suggest that a moderate dose of caffeine attenuates negative reactions in novice female blood donors and may increase the likelihood of repeat donations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lithium protection against oxygen toxicity in rats: ammonia and amino acid metabolism

1. The use of Li pre-treatment in rats before high pressure oxygen exposure has been reported effective in controlling convulsions. This is an effect which is better demonstrated if exposure to oxygen follows shortly after Li injection than exposure following several hours later. 2. This study has investigated the hypothesis that the protective action of Li may be exerted, in the short term, by its removing ammonia from the blood and alleviating the latter's known toxic action. 3. A normal Li distribution time profile in unstressed rat brain and blood following intraperitoneal injection has been established. Brain and blood ammonia, amino acids and Li concentrations were also measured in Li-treated animals exposed and convulsed by oxygen. These measurements were made both shortly (15 min) and also several hours after (24 hr) Li treatment. Ammonia and amino acid values in Li-protected groups were compared to normal unstressed animal values and also to values in animals convulsed by oxygen unprotected by Li pre-treatment. 4. In rat brain abd blood significant (P less than 0-001) elevation of ammonia and glutamine and depression of gamma-amino butyric acid (brain only) and glutamate was noted following oxygen treatment in unprotected animals. Prior injection of Li 15 min before high pressure oxygen exposure delayed convulsions twice as long. Additionally if these animals were only exposed to oxygen for a period of time equal to that which would normally produce convulsions in unprotected animals, brain and blood ammonia and amino acids were maintained near to unstressed animal levels. Concomitantly, blood Li concentrations were considerably depressed below the values one would expect from the previously determined Li distribution time profile. 5. In rats exposed to high pressure oxygen 24 hr after Li treatment there was no protective action against high pressure oxygen convulsion, rather a potentiating effect for convulsion was seen. 6. These data present compelling evidence for the controlling effect of Li in rats, on rising blood ammonia concentration which occurs in high pressure oxygen exposure. The effect might well be due to the known chelating properties of Li with ammonia.     

Cholecystokinin attenuates incentive learning in rats.

The hypothesis that endogenous cholecystokinin (CCK) reduces the incentive value assigned to food was examined by training undeprived rats to lever press and chain pull, with one action earning food pellets and the other maltodextrin solution. All animals were then food deprived and reexposed to one outcome after an injection of CCK-8 and the other after an injection of vehicle (VEH). When maintained food deprived and given a choice between the lever and chain in an extinction test, the rats performed fewer of the action trained with the outcome that was reexposed under CCK whether tested under CCK or VEH. In a subsequent experiment, this preference was attenuated by coadministration of the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2(di-n-propylamino)tetralin during reexposure, suggesting that CCK interacts with 5-HT to modify incentive value. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phosphatidylcholine synthesis and pulmonary oxygen toxicity

That organisms cannot remember events occurring during infancy may be the result of common forgetting processes exacerbated by the organism's increase in size during development or a unique process such as insufficient neurological development at the time of the early experience. To establish the uniqueness of infantile forgetting, size change was made irrelevant by exposing infant rats to "off-baseline" Pavlovian fear conditioning and assessing the effect of an apparatus-free conditioned stimulus upon independently established bar pressing. In Experiment 1, bar pressing by rats exposed to Pavlovian contingencies when 20-22 days old was substantially suppressed by the conditioned stimulus both 1 and 42 days after conditioning. In Experiment 2, pups conditioned when 17-19 and 20-22 days old again showed excellent retention, whereas pups conditioned when 11-13 and 14-16 days old showed total forgetting 42 days later. In Experiment 3, pups conditioned when 14-16 days old remembered well after 5 days, less well 10 days later, and not at all after 20 days. These findings suggest that size change may contribute to the forgetting of events occurring late in development, but that neurological immaturity may underly the forgetting of earlier events.     

Exercise attenuates oral intake of amphetamine in rats

The effects of wheel running on oral intake of amphetamine were examined in six male Sprague-Dawley rats given a 0.075-mg/ml amphetamine sulfate solution as their sole source of liquid, six rats given a 0.15-mg/ml amphetamine solution, and four rats given water as their sole source of liquid. All animals were housed in Wahmann running wheels and adjoining cages, and had ad lib access to ground Purina Chow. For the first 7 days of the experiment, the doors to the running wheels were closed; the wheels were then opened for 6 days. This cycle was repeated a second time. Animals drinking the 0.15-mg/ml amphetamine solution consumed significantly less food and gained less weight than animals in the other two groups. Although there was no difference in food intake between rats drinking water and rats drinking the 0.075-mg/ml amphetamine solution, rats in the water group gained significantly more weight than rats in the 0.075-mg/ml amphetamine group. With respect to drug intake, rats consumed significantly less amphetamine when running in the wheels than when access to the wheels was prohibited. Access to running wheels did not alter water intake. These latter results suggest that drug intake can be reduced by the provision of an alternate behavior.     

Low-dose midazolam attenuates predatory odor avoidance in rats

Based on the premise that optimal drug delivery might improve the efficacy of locoregional treatment for solid tumors, the authors set up an experimental model for isolation perfusion in surgical specimens from patients resected for carcinoma of the colon. Ten surgical specimens were cannulated, washed internally and externally with saline solution, promptly cooled to 4 degreesC, connected to a circuit, and perfused with Krebs-Henselait modified solution, concentrated red blood cells, albumin, desamethasone, glucose, and heparin for 60 minutes at a target temperature of 37 degreesC. Organ temperature, flow rate, perfusion pressure, and metabolic and functional parameters were checked at 5, 20, and 60 minutes of perfusion. A paraphysiologic perfusion procedure was achieved. Mean values (and ranges) were as follows: temperature 37 degreesC (35. 1-39.6 degreesC); flow rate 10.2 (5.6-17.9) ml/min/100 g; arterial pressure 96 (42-154) mmHg; arterial pH 7.3 (7.1-7.5); arterial PO2 183 (78-304) mmHg; arterial PCO2 36 (31-46) mmHg. No important signs of tissue damage were found at histology. Autonomous or stimulated peristalsis (or both) was present throughout the experiment. Mean O2 extraction was 7.9 ml/min/100 g (range 3.1-11.0). Mean glucose consumption was 229 mg/100 g (range 174-252). The model worked well and appears promising, particularly for future use in various pharmacokinetic and pharmacodynamic studies of antiblastic agents.     

CNS regulation of blood lactate concentration in anesthetized rats

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.     

Dietary L-arginine attenuates blood pressure in mineralocorticoid-salt hypertensive rats

The present study was designed to investigate the influence of dietary L-arginine supplementation on blood pressure and on ex vivo vascular reactivity in mineralocorticoid-salt (DOCA-salt) hypertensive rats. Systolic blood pressure and heart rate were determined throughout the experimental period in unanaesthetized rats. Plasma and urine electrolyte levels were measured. Vasoconstrictor response to noradrenaline and vasodilator responses to acetylcholine and sodium nitroprusside were evaluated in the isolated perfused mesenteric vascular bed. DOCA-salt hypertensive rats were divided into 2 groups: a control group and a treated group receiving 0.8% L-arginine supplementation in drinking water. Dietary L-arginine supplementation attenuated systolic blood pressure in conscious DOCA-salt hypertensive rats, but did not modify heart rate. Plasma calcium and sodium concentrations and urinary magnesium excretion were decreased by L-arginine supplementation. Noradrenaline-induced vasoconstriction decreased and acetylcholine-induced vasodilatation increased, whereas sodium nitroprusside-induced vasodilatation was not modified, in the L-arginine-supplemented rats. It is concluded that dietary L-arginine supplementation in the diet lowers systolic blood pressure in DOCA-salt hypertensive rats, probably through vascular action.     

Long-term toxicity study quillaia extract in rats

Tannic acid fixation reveals differences in the number of protofilaments between microtubules (MTs) in the nematode Caenorhabditis elegans. Most cells have MTs with 11 protofilaments but the six touch receptor neurons (the microtubule cells) have MTs with 15 protofilaments. No 13-protofilament (13-p) MT has been seen. The modified cilia of sensory neurons also possess unusual structures. The cilia contain nine outer doublets with A subfibers of 13 protofilaments and B subfibers of 11 protofilaments and a variable number of inner singlet MTs containing 11 protofilaments. The 15-p MTs but not the 11-p MTs are eliminated by colchicine-treatment or by mutation of the gene mec-7. Concomitantly, touch sensitivity is also lost. However, whereas colchicine treatment leads to the loss of all MTs from the microtubule cells, mutations in mec-7 result in the partial replacement of the 15-p MTs with 11-p MTs. Benzimidazoles (benomyl and nocodazole) have more general effects on C. elegans (slow growth, severe uncoordination, and loss of processes from the ventral cord) but do not affect the 15-p MTs. Benomyl will, however, disrupt the replacement 11-p MTs found in the microtubule cells of mec-7 mutants. The 11-p and 15-p MTs also respond differently to temperature and fixation conditions. It is likely that either type of MT will suffice for the proper outgrowth of the microtubule cell process, but only the 15-p MT can function in the specialized role of sensory transduction of the microtubule cells.     

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice

We evaluated ethanol- and HCl-induced mucosal damages in developing rats. The degree of damage induced by ethanol and HCl was greatest in 1-week-old rats and decreased significantly with age until 4 weeks; thereafter it increased again. To evaluate the effect of weaning on the maturational changes in mucosal defense, we compared ethanol-induced mucosal damage among three groups of newborn rats: (1) receiving milk only; (2) receiving only rat chow from 14 days of age, and (3) having free access to milk and chow. There were no significant differences at 18 and 21 days of age. The mucus thickness increased with age until 8 weeks and was not affected by weaning. In conclusion, developmental changes occur in gastric mucosal protection in rats. Weaning does not have a significant effect on these changes.     

Neuropeptide Y antibody attenuates 2-deoxy-D-glucose induced feeding in rats

2-deoxy-D-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake.     

Chlordiazepoxide attenuates activity-induced anorexia and weight loss in rats.

Studied the effects of chlordiazepoxide (CDP) on body weight and food intake in male rats. In Exp 1, the effect of repeated injections of 2.5, 5.0, or 10.0 mg/kg of CDP on food intake and body weight was studied in rats on an activity anorexia (AA) regimen. For several days before CDP testing began, rats lived in activity wheels and had one 60-min meal/day. During CDP testing, this regimen continued except that each rat was injected with an appropriate dose of CDP or saline 30 min before each meal. CDP enhanced food intake; 5.0 mg/kg seemed most effective. However, the CDP-induced increase in eating did not noticeably stem weight loss. In Exp 2, after several days of AA training, CDP (5.0 mg/kg) was tested under less severe conditions; food remained restricted, but access to the wheels was discontinued. Rats given CDP ate more and gained more weight than controls. These findings suggest that benzodiazepines such as CDP may help in treating anorexia nervosa and other anorectic conditions in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Twenty-six-week oral toxicity study of benzalazine in rats

A 26-week toxicity study by oral gavage administration was performed in Sprague-Dawley rats with benzalazine (2-hydroxy-5-[(4-carboxyphenyl) azo] benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, as a part of a safety evaluation program. Dosages of 0 (control), 300, 900 and 2700 mg/kg b.w./d were selected for this study. Except slight changes in the urinary status (decreased pH value and increased specific gravity) from 900 mg/kg b.w./d p.o. onwards, which were probably substance related, no further intolerance reactions were observed. The urine had a dark-yellow colour which was probably an indication of metabolites of benzalazine or benzalazine itself which were excreted via the urine. Behaviour, external appearance, body weight gain, food and water consumption, haematology, clinical biochemistry, organ weight analysis, macroscopic and microscopic examinations revealed no substance-related influence. Therefore, on the basis of the results obtained, it is concluded that the non-toxic dose level in this study is considered to be 300 mg benzalazine/kg b.w./d p.o. following daily administration for 26 weeks.     

Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity

OBJECTIVE: To study type IV collagen of skin and serum in patients with ALS. BACKGROUND: Collagen abnormalities of skin have been reported in ALS patients. However, little is known concerning type IV collagen in ALS. METHODS: We studied type IV collagen immunoreactivity of skin and measured serum levels of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in patients with ALS and control subjects. RESULTS: The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for type IV collagen as compared with those of diseased control subjects. This weak immunostaining became more pronounced as ALS progressed. The optical density for type IV collagen immunoreactivity in ALS patients was significantly lower (p < 0.001) than in diseased control subjects and was significantly decreased with duration of illness (r = -0.85, p < 0.01). Serum 7S collagen levels in patients with ALS were significantly decreased (p < 0.01) as compared with those in diseased and healthy control subjects and were negatively and significantly associated with duration of illness (r = -0.81, p < 0.001). There was an appreciable positive correlation between concentrations of serum 7S collagen and the density for type IV collagen immunoreactivity in ALS patients (r = 0.81, p < 0.02). CONCLUSIONS: These data suggest that a metabolic alteration of type IV collagen may take place in the skin of ALS patients and that the decreased levels of serum 7S collagen may reflect a decreased type IV collagen immunoreactivity of skin in patients with ALS.     

BDNF attenuates functional and structural disorders in nerves of galactose-fed rats

Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.     

Conditioned brain-stimulation reward attenuates the acoustic startle reflex in rats.

The acoustic startle reflex (ASR) in rats is attenuated by a light paired with food or, in humans, by "pleasant" pictures. Rats were trained to barpress for lateral hypothalamus (LH) stimulation. ASR amplitudes were then measured at 4 intensities, with or without a light. Control rats that did not receive brain-stimulation reward (BSR) showed initially lower ASR amplitudes than did rats exposed to BSR, but both groups responded similarly with or without light. Next, experimental rats were given BSR in the presence of light but not in its absence. After conditioning, ASR amplitudes were reduced, and ASR thresholds were raised by a mean of 2.6 dB in the light but remained at preconditioning levels without light. No such change was found for control rats or rats with placements outside the LH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glycine attenuates Fanconi syndrome induced by maleate or ifosfamide in rats

It has become widely recognized that glycine (Gly) depletion predisposes isolated proximal tubules (PT) to necrotic cell damage induced by diverse insults and that Gly replacement in vitro is highly cytoprotective. However, the effectiveness of supplementation with Gly in vivo, where blood and tissue Gly normally are maintained at high levels, is incompletely defined. Our aim was to assess whether: (a) supplementation of Gly in drinking water of rats would attenuate the proximal tubule damage and the Fanconi syndrome (FS) induced by maleate (Mal), a classical proximal tubule toxin, or ifosfamide (IFO), an antineoplastic drug; and (b) to explore the mechanisms responsible for such effects, since Gly supplementation might be especially beneficial in treating the FS, where the kidney tends to waste amino acids. Rats received daily injection of Mal (2 mmol/kg) for two days without or with oral supplementation of 2% Gly. IFO, 50 mg/kg, was injected daily for five days without or with oral Gly. Control rats were injected with saline, without or with oral Gly. The results demonstrated that both Mal and IFO induced a FS characterized by wasting of amino and organic acids, glucose, and electrolytes, along with elevated plasma creatinine (Crn) and BUN, and decreased Crn clearance rate. Light microscopy revealed a necrotic lesion in the proximal tubules of the Mal group, but no necrosis after IFO. Gly strongly ameliorated the severity of renal necrosis and/or dysfunction induced by Mal or IFO, with significant decreases in total and fractional excretion of Na+, K+, PO4(3-) and glucose, decreased plasma BUN and Crn, and increased Crn clearance. Analysis of freeze-clamped cortical tissue showed substantial depletion of [Gly], [ATP] and [GSH] along with increased GSSG in Mal or IFO groups and correction of [Gly] and [ATP] with Gly supplementation, but no improvement with Gly of reduced gluthatione [GSH] or the ratio of reduced to oxidized gluthatione (GSH/GSSG). 31P-NMR analysis of the renal cortex indicated a decrease in Pi and various membrane phospholipids in Mal and IFO rats and prevention of this damage with Gly. These observations demonstrate that oral supplementation of Gly can provide protection against Mal or IFO-induced renal tubular cell dysfunction and structural damage. The lack of effect on glutathione oxidation and depletion suggests an action distal to toxin uptake and intracellular interactions, which is similar to the characteristics of Gly cytoprotection against diverse insults in vitro. The results also suggest modification by Gly of the primary toxicity of the agents and effects on phospholipid synthesis that could contribute to repair.