Anionic copolymerization of acrolein with aldehydes

Unsaturated copolyacetals have been prepared by anionic copolymerization of acrolein with aldehydes, such as, acetaldehyde, benzaldehyde, propionaldehyde, pivaldehyde and others. The dependence of the structure of the copolymers on the dielectric constant of the solvent, and on the temperature, the aldehyde, the catalyst and the extension of the reaction has been studied.     

Recovery of mouse neuromuscular junctions from single and repeated injections of botulinum neurotoxin A

Botulinum neurotoxin type A (BoNT/A) paralyses muscles by blocking acetylcholine (ACh) release from motor nerve terminals. Although highly toxic, it is used clinically to weaken muscles whose contraction is undesirable, as in dystonias. The effects of an injection of BoNT/A wear off after 3–4 months so repeated injections are often used. Recovery of neuromuscular transmission is accompanied by the formation of motor axon sprouts, some of which form new synaptic contacts. However, the functional importance of these new contacts is unknown. Using intracellular and focal extracellular recording we show that in the mouse epitrochleoanconeus (ETA), quantal release from the region of the original neuromuscular junction (NMJ) can be detected as soon as from new synaptic contacts, and generally accounts for > 80% of total release. During recovery the synaptic delay and the rise and decay times of endplate potentials (EPPs) become prolonged approximately 3-fold, but return to normal after 2–3 months. When studied after 3–4 months, the response to repetitive stimulation at frequencies up to 100 Hz is normal. When two or three injections of BoNT/A are given at intervals of 3–4 months, quantal release returns to normal values more slowly than after a single injection (11 and 15 weeks to reach 50% of control values versus 6 weeks after a single injection). In addition, branching of the intramuscular muscular motor axons, the distribution of the NMJs and the structure of many individual NMJs remain abnormal. These findings highlight the plasticity of the mammalian NMJ but also suggest important limits to it.     

Metabolism of intracellular zinc and copper following single and repeated injections of gold sodium thiomalate

Repeated injections of gold sodium thiomalate were given to Wistar rats and the effect of gold on the binding of endogenous zinc and copper to the cytosolic proteins in the liver and kidneys was studied. The tissue levels of gold and the tissue uptake of zinc and copper as a function of gold dose was also studied. The result of the multiple-dose study show that in the liver the tissue gold levels rose rapidly following the first five gold injections (one injection/week) and then stabilized. In the kidneys the gold concentrations continued to increase with each additional dose. Uptake of zinc into the high molecular weight proteins (MW>60,000 daltons) and the superoxide dismutase fractions were significantly increased following the repeated gold injections in the liver and kidney cytosol. The uptake of copper into the high MW proteins were decreased in the liver as well as the kidneys. Copper levels in the superoxide dismutase and the low MW (<4000 daltons) fractions initially increased then decreased from the sixth gold dose onwards (possibly related to the overall decrease in tissue copper levels in the liver). The incorporation of copper into the hepatic metallothioneins appeared to be unaltered. In the kidney cytosol, the uptake of copper was significantly increased into the metallothionein fractions. The uptake into the other fractions decreased over the multiple-dose period. Gold sodium thiomalate increased the tissue concentration of zinc in the liver as well as the kidneys. The level of copper in the liver was decreased and that in the kidneys increased. Practically all the additional copper in the kidneys was incorporated in the thioneins. These observations indicate that gold sodium thiomalate has a major role in providing a stimulus for the liver, kidney and perhaps other cells to bring about a redistribution of body zinc and copper. The various cytosolic proteins, including the inducible metalloproteins, superoxide dismutase and metallothioneins, seem to help the cell carry out this task. In view of the importance of these essential metals in physiological processes of relevance to rheumatoid arthritis, it is suggested that gold salts may mediate, to some extent, their antiarthritic activity through an effect on the metabolism of zinc and copper.     

Kinetics of [14C]phenazepam excretion in albino rats after single and repeated injections of the drug

During the 5 days after intraperitoneal injection of [¹⁴C] phenazepam into albino rats, both intact animals and animals previously receiving phenazepam injections for 15 days, about 77% of the total radioactivity was excreted with the urine and feces. The excretion processes can be described by a first-order equation. The rate of total excretion of phenazepam was identical after single or repeated injections of the drug. Meanwhile, after a single injection of phenazepam into the animals, it was excreted mainly with the urine, whereas after repeated injections it was excreted mainly with the feces. The process of excretion of phenazepam with the urine after repeated injection is biexponential in character.Laboratory of Psychotropic Drugs, I. I. Mechnikov Odessa University. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 561–563, June, 1979.     

Developmental effects of oxytocin on stress response: single versus repeated exposure

Both exogenous and endogenous oxytocin (OT) are associated with an attenuated stress response. Increased levels of OT in the early postnatal period have been shown to affect behavior and physiology in rodents, and these effects last into adulthood, suggesting an organizational role for OT during development. We investigated the effects of neonatal exposure to OT on the development of the stress response in male and female prairie voles (Microtus ochrogaster). OT or an OT antagonist (OTA) was administered either on postnatal day 1 (single, D1) or days 1-7 (repeated, D1-7) and then on day 8 the response to social isolation was assessed by quantifying ultrasonic vocalizations (USVs) and measuring plasma corticosterone (CORT). Treatment effects were observed only in females. A single treatment with OTA was associated with a decrease in vocalizations, while repeated treatment produced an increase in vocalizations. A single treatment with either saline or OTA increased basal CORT. The results suggest that endogenous OT may be involved in the development of the stress response in females.     

The effects of intracellular injections of phosphate on intracellular calcium and force in single fibres of mouse skeletal muscle

Intracellular inorganic phosphate increases during muscle fatigue and may be responsible for certain of the changes in muscle function observed in fatigue. To test this hypothesis inorganic phosphate was micro-injected in single mouse muscle fibres which were also injected with indo-1 to measure intracellular Ca²⁺. Following phosphate injection, intracellular Ca²⁺, both at rest and during tetani, was reduced as was tetanic force. The rate at which the sarcoplasmic reticulum (SR) pumped Ca²⁺ out of the myoplasm was accelerated following phosphate injection. Intracellular Ca²⁺ and force recovered over 1-h. The changes in maximum Ca²⁺-activated force and Ca²⁺ sensitivity which would be expected if the phosphate remained in the myoplasm were largely absent. The most likely interpretation is that inorganic phosphate enters the SR where it precipitates with Ca²⁺ and thereby reduced release of Ca²⁺ from the SR and accelerated the rate of uptake of Ca²⁺ by the pump. The 1-h recovery may represent the entry of additional Ca²⁺ into the cell to reestablish the normal gradient of Ca²⁺ across the sarcolemma. Received: 21 August 1995 /Received after revision: 23 October 1995 /Accepted: 6 November 1995     

Comparison of the effects of physical exercise, cold acclimation and repeated injections of isoprenaline on rat muscle enzymes.

The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.     

The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats

Repeated administration of amphetamine-like psychostimulants produce a progressive and long-lasting hypersensitivity to their behavioural effects known as behavioural sensitization. Previous studies have shown that administration of the purinergic P2 receptor agonist 2-methylthio ATP into the nucleus accumbens of rats raises the extracellular level of dopamine accompanied with enhanced locomotion in a similar manner. Furthermore, the quantitative EEG after application of 2-methylthio ATP or amphetamine was characterized by an elevation of the alpha1-power. However, purinergic P2 receptor antagonists decreased the basal level of dopamine in the NAc and in addition prevented the effects of 2-methylthio ATP. The purpose of the present study was to investigate, whether endogenous ATP acting via purinergic P2 receptors is involved in the process of amphetamine-induced sensitization. Rats were treated systemically for five successive days with d-amphetamine (1.5 mg/kg) and tested in an open field with respect to their locomotor response. The enhanced locomotor activity after the first injection of amphetamine was diminished by the previous intracerebroventricular application of the purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS; 0.6 nmol) (P<0.05). The challenge with a lower dose of amphetamine (0.75 mg/kg) produced an increased locomotion in comparison to the response after the first amphetamine application indicating the expression of a behavioural sensitization. Pretreatment with PPADS prior to each amphetamine administration prevented the increase of locomotor activity after the challenge with amphetamine (P<0.05). In summary, the present study demonstrates that PPADS blocks both the acute locomotor effects of amphetamine and the development of behavioural sensitization to the psychostimulant. We suggest that the activation of purinergic P2 receptors by endogenous ATP is necessary for the expression of these effects.     

糖皮质激素注射建立小鼠行为抑郁症模型

目的研究糖皮质激素注射小鼠抑郁症样情感行为变化。方法C57/B6雄性小鼠18只随机分为3组,模型组以20 mg/kg剂量每日1次注射皮质酮,持续21 d,另有生理盐水对照组每日注射等剂量生理盐水21 d,空白对照组不做任何处置,观察小鼠体重变化,用敞箱实验及糖水消耗试验测定动物行为。结果抑郁模型组小鼠代表焦虑行为的敞箱试验得分明显降低、反应快感行为的奖赏糖水消耗百分比明显降低。结论糖皮质激素持续注射法可用于制作行为小鼠抑郁模型,以及探究抑郁症行为变化发病机制以及寻找更适合治疗抑郁症的药物。     

The effects of acute or repeated cocaine administration on nerve terminal glutamate within the rat mesolimbic system

Cocaine administration alters glutamate function within several brain regions. Using quantitative electron microscopic immunocytochemistry, the present study investigated the effect of repeated intermittent cocaine (resulting in behavioral sensitization) or acute cocaine administration on the density of glutamate immunogold labeling within nerve terminals. Rats were treated daily with saline or cocaine for 7 days. Following a 14-day withdrawal animals were challenged with saline or cocaine. On the challenge day, most (75%) animals that received cocaine repeatedly showed a heightened locomotor response to cocaine compared to the first day of cocaine administration, and were considered behaviorally sensitized.Three days after the challenge, glutamate immunogold labeling was quantified in nerve terminals making asymmetrical synaptic contacts within the core and shell of the nucleus accumbens, ventral tegmental area and medial prefrontal cortex. There was a decrease in such labeling in the nucleus accumbens in the group receiving acute cocaine. Locomotor activity was positively correlated with glutamate immunolabeling within nerve terminals in the nucleus accumbens core only for the cocaine-sensitized group. Nerve terminal glutamate immunolabeling in the nucleus accumbens core, but not the shell, was increased in the non-sensitized compared to the cocaine-sensitized group. In the ventral tegmental area, glutamate immunolabeling was significantly higher in the cocaine-sensitized compared to the acute cocaine group. In the prefrontal cortex, there were no significant differences in glutamate immunogold labeling between treatment groups.This study indicates that acute cocaine administration significantly decreases nerve terminal glutamate immunoreactivity in the nucleus accumbens. We suggest that sensitization results in differential changes in the nucleus accumbens core versus the shell, and may alter presynaptic mechanisms regulating glutamate release or re-uptake in the core.