Inhibitory effect of ouabain on epinephrine-induced stimulation of adrenal corticosterone secretion in rats.

Chronic administration of ouabain (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) definitely inhibited epinephrine-induced increase of adrenal corticosterone secretion. The inhibition rate increased along with frequency of ouabain administration. Increase in adrenal corticosterone synthesis and secretion by ACTH (20-50 mU/rat) administration was partially suppressed by pretreatment with chronic ouabain administration. A slight but significant increase of adrenal corticosterone secretion caused by epinephrine administration in hypophysectomized rats was also inhibited by pretreatment with ouabain administration. Chronic administration of neither phentolamine (1 mg/rat, intraperitoneally, once daily for consecutive 15 days) nor propranolol (3 mg/Kg body weight, subcutaneously, once daily for consecutive 15 days) caused significant changes in adrenal corticosterone secretion in response to ACTH as well as to epinephrine. Chronic administration of ouabain in rats causes not only elevated secretion of ACTH from anterior pituitary but also functional change in adrenals leading to suppression of corticosterone secretion in response to ACTH or epinephrine administration.     

Convulsive Activity of α-Guanidinoglutaric Acid and the Possible Involvement of 5-Hydroxytryptamine in the α-Guanidinoglutaric Acid-Induced Seizure Mechanism

alpha-Guanidinoglutaric acid (alpha-GGA) was first found in cobalt-induced epileptogenic focus tissue in the cerebral cortex of cats. We examined the effect of alpha-GGA on the electroencephalogram and on the brain 5-hydroxytryptamine (5-HT) level after intraventricular administration into rats. Sporadic low-voltage spikes appeared 4 min after the administration of alpha-GGA. Spikes increased in voltage 6 min after the administration. Multiple spikes appeared 10 min after the administration, and they reached maximal frequency 30 min after the administration. The epileptic discharges disappeared 100 min after the administration. The 5-HT level increased in the right and left cortices 3 min after the administration. The 5-HT level decreased in the mid-brain 5 min after the administration and subsequently in all regions of the brain 10 min after the administration. No change in the 5-HT level was found 30 min and 100 min after the administration. These results show that alpha-GGA induces epileptic seizures in rats after intraventricular administration. The results also suggest that alpha-GGA-induced seizures are associated with abnormal serotonergic function and that they are initiated by a decrease in the 5-HT level.     

The Incorporation of Orally Administered Radioiodine Into Hens’ Eggs and Follicles

Incorporation of radioiodine into eggs and follicles was studied by oral administration of I131 to hens. With the single dose administration of I131 the shell, including the shell membranes, reached a maximal concentration of 0.017 % of the given amount per g of shell in eggs laid within one day after administration. The white reached a maximal concentration of 0.01 % per g in eggs laid about one day after administration. The subsequent reduction in concentration both in the shell and white from later laid eggs showed a rapid course. In the yolk, radioiodine began to appear in eggs laid about one day after administration. A maximal concentration of 2.78 % of the given amount per yolk was reached in eggs laid about five days after administration. The subsequent reduction in concentration could be followed in the yolk from eggs laid up to and including the ninth day after administration; then the concentration was about 1/50 of the maximal concentration. With continuous administration of I131 once daily for 16 days, the concentration in the shell and white was in the same amount as corresponding maximal concentration in single dose administration as long as the daily supply continued. Following cessation of administration, the concentration decreased in the shell and white with a course simliar to that obtained in the single dose administration. In the yolk, the concentration increased in eggs laid up to and including the ninth day after commencement of the continuous dosing; thereafter, the equilibrium remained as long as the administration continued. About 13 % of the daily given dose of I131 was recovered per yolk. After discontinuation of administration, an obvious concentration reduction was first obtained in the yolks from eggs laid five days later. A calculation of the results for the yolks from the single dose administration to be valid for the daily continuous dosing showed good agreement with the results obtained in the present multiple dose experiments. The follicular uptake of I131 in single dose administration was rapid, with the greatest uptake by the follicle which was in the most rapid phase of growth at the time of administration. During autoradiography of the follicles and eggs following single dose administration of I131, most of the radioiodine was recovered in the growth zone which corresponded to the follicle’s development during the first day after administration.     

Hormonal control of metabolism of gamma-aminobutyric acid in the rat hypothalamus and hippocampus

It has been established that hydrocortisone administration increased the amount of total, free, bound and synaptosomal GABA in the hypothalamus, glutamate decarboxylase activity in the homogenate and synaptosomes and time of the mediator turnover. ACTH administration increased the GABA content and glutamate decarboxylase activity in synaptosomes. The total amino acid content and time of its turnover got higher only with single hormone administration. In the hippocamp hydrocortisone administration increased the total and free GABA contents, its turnover time, glutamate decarboxylase activity in the homogenate and decreased GABA-aminotransferase activity in the homogenate and synaptosomes. The GABA level in synaptosomes grew only with multiple hormone administration. Single administration of ACTH decreased the total GABA content, glutamate decarboxylase activity in the homogenate, while its multiple administration increased the GABA level in synaptosomes followed by a decrease of GABA-aminotransferase activity in the homogenate and synaptosomes. The GABA turnover time fell with single hormone administration and grew with the multiple one. Adrenalectomy induced no changes in the GABA content and activity of its metabolism enzymes in the hypothalamus, however the bound GABA level decreased, while the turnover time increased. In the hippocamp adrenalectomy decreased total, free and synaptosomal GABA contents, glutamate decarboxylase activity in a homogenate and turnover time. Subsequent hydrocortisone administration only partly normalized the revealed changes of the GABA metabolism in the brain structures under adrenalectomy.     

Formation of gamma-aminobutyric acid from glutamate and putrescine in rat hypothalamic and hippocampal synaptosomes and regulation of these processes by glucocorticoids]

It has been shown that single or multiple hydrocortisone and ACTH administrations to intact rats increased GABA content and its synthesis from glutamate and putrescine in synaptosomes of hypothalamus. The letter content was increased by single hormonal administration while multiple hormonal administration and adrenalectomy decreased it. Ornithine decarboxylase activity was increased by single hydrocortisone administration to intact animals, following adrenalectomy, and it was decreased by single hormonal administration to adrenalectomized rats. GABA synthesis in synaptosomes of hippocampus from putrescine was increased by single hydrocortisone and multiple hormonal administrations. GABA content was increased by multiple administration of both hormones and was decreased by adrenalectomy. Putrescine level was decreased by multiple hydrocortisone administration to intact and single administration to adrenalectomized rats; ornithine decarboxylase activity was decreased by multiple administration of both hormones.     

Clinical pharmacokinetics of kanamycin in endolymphatic therapy of peritonitis]

The pharmacokinetics of kanamycin in patients with peritonitis was studied after its intramuscular, endolymphatic and lymphotropic administration. Endolymphatic administration of kanamycin provided an increase in its activity in the inflamed tissues of the peritoneum and omentum and markedly prolonged its halflife as compared to those after the routine intramuscular administration of the drug. Lymphotropic administration of kanamycin failed to provide the same effect. Endolymphatic therapy of the patients during the postoperative period provided a decrease in the lethality, development of complications and the terms of the treatment in the hospital. The therapeutic effect of the endolymphatic administration of kanamycin to the patients with peritonitis proved to be high. The more efficient antibiotic therapy of the cases was likely due to favourable shifts in the pharmacokinetics of kanamycin after its endolymphatic administration.     

Specific binding of H3-GABA by synaptic membranes of hypothalamus and hippocampus in rats after adrenalectomy and administration of hydrocortisone and corticosterone]

It has been shown that single hydrocortisone administration increased 3H-GABA binding by hypothalamic synaptic membranes. ACTH administration enhanced binding in both studied brain structures. Multiple hydrocortisone administration did not effect 3H-GABA binding by hypothalamic and hippocampal membranes, while multiple ACTH administration caused the decrease in mediator binding by hypothalamic membranes and increased its level in hippocampal membranes. Adrenalectomy did not change 3H-gaba binding and single hydrocortisone administration to adrenalectomized rats increased 3H-GABA binding only by hypothalamic synaptic membranes.     

Effect of intraventricular administration of noradrenaline and dopamine on the levels of corticosterone in rats and denervation hypersensitivity resulting from intraventricular administration of 6-hydroxydopamine.

The effects of intraventricular administration of noradrenaline (NA) on the resting levels, stress-induced rises and dexamethasone-induced decreases of plasma corticosterone (B) were studied in rats. The effect of pretreatment with intraventricular administration of 6-hydroxydopamine (6-OHDA) on the effects of NA or dopamine (DA), which was injected intraventricularly, was also examined. The results obtained were as follows: 1) Intraventricular administration of 1.0 μg of NA did not cause a decrease in concentrations of plasma B. 2) Ten μg of NA injected intraventricularly resulted in a rise of the levels of plasma B. 3) The stimulating action of centrally administered NA was more marked when the pre-injection concentrations of B were lower. 4) Pretreatment with intraventricular administration of 6-OHDA facilitated the action of intraventricularly administered NA in the regulation of pituitary-adrenocortical functions. The result suggests a development of denervation hypersensitivity caused by the pretreatment. 5) Intraventricular administration of NA did not block stress-induced rises of plasma B. 6) Intraventricular administration of NA counteracted dexamethasone-induced decrements of plasma B. 7) This counteraction was enhanced by pretreatment with intraventricular administration of 6-OHDA. This also suggests a development of denervation hypersensitivity resulting from intraventricular administration of 6-OHDA. 8) Intraventricular administration of 1.0 μg of DA caused no change in the concentrations of plasma B in either control or 6-OHDA treated animals.     

Nootropic and analgesic effects of Semax following different routes of administration

Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.     

Influence of choline and ethanolamine administration on choline and ethanolamine phosphorylating activities of mouse liver and kidney.

The administration of ethanolamine to adult male mice resulted in a significant increase in ethanolamine kinase activity in liver and kidney. Similarly, choline administration resulted in a significant increase in choline kinase activity in liver and kidney. The administration of ethanolamine resulted in enhancement of choline kinase activity concomitantly with ethanolamine kinase activity in liver and kidney. The administration of choline, however, did not result in any significant increase in ethanolamine kinase activity in liver or kidney. Cycloheximide administration along with choline-ethanolamine prevented the increase in kinase activity in liver and kidney. The results obtained have been discussed in relation to the regulatory role of choline kinase and ethanolamine kinase by de novo synthesis in response to enhanced substrate concentration, the secondary nature of choline kinase induction on ethanolamine administration, and possible distinction between choline kinase and ethanolamine kinase.     

Increased tolerance of the dopamine- and serotoninergic systems during chronic administration of haloperidol and levomepromazine

In experiments on male albino rats single administration of haloperidol produced catalepsy, increase in dopamine turnover, enhancement of main dopamine metabolite homovanilinic acid in the forebrain. After single administration of the levomepromazine the cataleptogenic effect was accompanied by an enhanced 5-hydroxyindole acetic acid level, and no influence on the dopamine metabolism was observed. During chronic administration of haloperidol and levomepromazine their ability to induce catalepsy and to increase homovanilinic acid or 5-hydroxyindoleacetic acid concentration diminished. Thus, it appears that chronic administration of haloperidol reduces the sensitivity of dopamine receptors, and chronic administration of levomepromazine--reduces the sensitivity of dopamine and serotonin receptors in the brain.     

Intranasal administration of ACTH(1-24) stimulates catecholamine secretion.

Previously, we reported that intranasal (IN) ACTH(1-24) administration stimulates adrenocortical steroid secretion in normal subjects. To determine the efficiency of transmucosal absorption of ACTH into the adrenal medulla, we measured serum cortisol, aldosterone, epinephrine, norepinephrine and dopamine levels after IN vs. intravenous (IV) administration of 250 microg ACTH(1-24) in 7 healthy adult men (mean age 21.7 +/- 1.2 yr; range, 21 - 24 yr). Blood was collected at 0, 30, 60 and 120 min after administration of ACTH(1-24), and the levels of adrenocortical steroids and catecholamines were measured by specific RIA and HPLC methods, respectively. There were no side effects associated with IN or IV ACTH administration. Consistent with the previous study, serum cortisol and aldosterone increased after IN administration of ACTH(1-24), peaking 30 min after administration. Sixty minutes after IN and IV administration of ACTH, epinephrine levels increased by 41.9 +/- 13.1 % and 63.3 +/- 11.8 %, respectively, and remained elevated throughout the sampling period. Thirty minutes after IN or IV administration of ACTH(1-24), plasma norepinephrine levels increased by 55.9 +/- 13.4 % and 73.7 +/- 15.0 %, respectively, peaking 30 min after ACTH(1-24) administration, and decreasing to basal levels within 60 min. Plasma dopamine levels did not change after IN administration of ACTH(1-24). Adrenocortical steroid and catecholamine levels did not increase after IN administration of saline. These results demonstrate that IN administration of ACTH(1-24) not only stimulates adrenocortical steroids, but also epinephrine and norepinephrine.     

Effect of acute and chronic administration of L- thyroxine and methimazole on blood levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in plasma of rats]

The effects of hyperthyreosis induced by the administration of thyroxine and hypothyreosis induced by the administration of methimazole on the levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in low-platelet blood plasma have been studied in Wistar rats. Thyroxine administration (120 micrograms/kg/24 h, intraperitoneally) lasting 7 days caused a decrease in serotonin concentration by 38 per cent. The level of this amine in rats receiving thyroxine during three months was elevated by almost three times. Tryptophane concentration did not change following thyroxine administration. Methimazole administration lasting 14 days (oral dose 15 mg/kg/24 h) caused an increase in tryptophane concentration by 34 per cent and in serotonin concentration by 24 per cent. Long-term hypothyreosis induced by methimazole administration lasting three months caused an 39 per cent increase in tryptophane and 38 per cent increase in serotonin concentration. Neither hyperthyreosis induced by thyroxine administration nor hypothyreosis induced by methimazole++ caused any changes in the concentration of 5-hydroxyindoleacetic acid. The importance of serotonin in pathogenesis of clinical symptoms accompanying the states of deficit or excess of thyroid hormones needs further elucidation.     

Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice

—Effects of acute or chronic administration of ethanol and its withdrawl on the steady-state levels and turnover rates of certain neurotransmitters have been investigated in mice. The influence of long-term administration of ethanol on the activities of enzymes involved in the metabolism of these transmitters has also been studied. Acute administration of ethanol or acetaldehyde or chronic administration of ethanol resulted in a decrease in the cerebral contents of acetylcholine, acetylCoA and CoA. Brain levels of 5-hydroxytryptamine, norepinephrine and choline remained unchanged after acute administration of ethanol. However, chronic administration of ethanol resulted in a decrease in the norepinephrine content without significantly affecting 5-hydroxytryptamine or choline contents. Cerebral levels of γ-aminobutyric acid increased with both acute or chronic administration of ethanol. The total incorporation of [³H]choline into acetylcholine in brain was depressed upon acute administration of ethanol. After withdrawal of ethanol for one day cerebral levels of norepinephrine returned to normal; however, γ-aminobutyric acid and acetylcholine returned to normal levels at 2 and 4 days after ethanol withdrawal, respectively. Pretreatment of mice with pyrazole, an inhibitor of alcohol dehydrogenase, prevented the ethanol-induced decrease in cerebral acetylcholine levels. The activities of cerebral choline acetyltransferase and glutamic decarboxylase were decreased after 2 weeks of chronic ethanol administration. However, the activities of acetyl cholinesterase and GABA-transaminase remained unaffected after 2 weeks of ethanol treatment     

Effects of Capsaicin and Isoflavone on Blood Pressure and Serum Levels of Insulin-Like Growth Factor-I in Normotensive and Hypertensive Volunteers with Alopecia

Insulin-like growth factor-I (IGF-I) reduces arterial blood pressure. Since administration of capsaicin and isoflavone increases serum levels of IGF-I by sensory neuron stimulation in subjects with alopecia, it is possible that administration of capsaicin and isoflavone reduces arterial blood pressure in patients with hypertension. Systolic and diastolic blood pressure (BP) and serum levels of IGF-I were determined before and at 1, 3, and 5 months after administration of capsaicin and isoflavone in 42 volunteers with alopecia, 29 normotensive and 13 hypertensive volunteers. Neither systolic nor diastolic BP changed in the normotensive volunteers after combined administration of capsaicin and isoflavone. In contrast, systolic and diastolic BP was significantly reduced in hypertensive volunteers after administration of capsaicin and isoflavone. Serum levels of IGF-I significantly increased in both normotensive and hypertensive volunteers after administration of capsaicin and isoflavone. These observations suggest that administration of capsaicin and isoflavone might reduce BP in hypertensive, but not in normotensive subjects, probably by increasing serum levels of IGF-I.     

Effect of Acute and Chronic Administration of Methylphenidate on Mitochondrial Respiratory Chain in the Brain of Young Rats

Methylphenidate is commonly used for the treatment of attention deficit/hyperactivity disorder. There are still few works regarding the effects of methylphenidate on brain energy metabolism. Thus, in the present study we evaluated the effect of chronic administration of methylphenidate on the activities of mitochondrial respiratory chain complexes I and III in the brain of young rats. The effect of acute administration of methylphenidate on mitochondrial respiratory chain complexes I, II, III and IV in the brain of young rats was also investigated. For acute administration, a single injection of methylphenidate was given to rats on postnatal day 25. For chronic administration, methylphenidate injections were given starting at postnatal day 25 once daily for 28 days. Our results showed that complexes I and III were not affected by chronic administration of methylphenidate. Moreover, the acute administration of methylphenidate decreased complex I activity in cerebellum and prefrontal cortex, whereas complexes II, III and IV were not altered.     

Concentrations of nitric oxide in equine preovulatory follicles before and after administration of human chorionic gonadotropin

In the present study, follicular fluids of estrous mares treated with saline solution (Control) or nitric oxide synthase (NOS) inhibitors were analyzed for nitric oxide (NO), estradiol-17beta (E2) and progesterone (P4) concentrations before and 36h after administration of human chorionic gonadotropin (hCG). Follicular fluids obtained before (0h) hCG administration from control mares had lower concentrations of NO than those obtained 36h after administration of hCG (58.3+/-17.8 micromol versus 340.4+/-57.7 micromol; P<0.05). A similar pattern was also noted for intrafollicular P4 in control mares, which had lower concentrations of intrafollicular P4 before hCG than 36h post-hCG administration (P<0.05). As expected, E2 concentrations of control follicles sampled before hCG administration were higher than those sampled 36h post-hCG administration (P<0.05). However, the E2 concentrations in follicles of mares treated with the NOS inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine (AG) did not decrease after hCG administration, unlike those in control mares (P>0.10). In addition, mares treated with NOS inhibitors had lower intrafollicular concentrations of NO and P4 than control mares, both before and after hCG administration (P<0.05). Increased intrafollicular concentrations of NO in control, hCG-stimulated mares provide evidence for the presence of an NO-generating system in the equine preovulatory follicle that is likely upregulated following administration of hCG.     

Alterations of lithium clearance in rats by different modes of lithium administration

This study examines the effects of acute versus dietary lithium administration on proximal tubular fluid output (Vprox) and sodium clearance in 6 groups of unrestrained, conscious rats. Vprox was estimated on the basis of the renal lithium clearance. The aim was to find the mode of lithium administration which least influences the proximal and distal reabsorption of sodium. The lithium doses used resulted in serum lithium concentrations between 0.2 and 0.3 mmol/l with no difference between the groups. Acute intravenous lithium administration increased lithium clearance by 40% and sodium clearance by 109%. Administration by gastric tube increased lithium clearance by 22% and sodium clearance by 78% in comparison to dietary administration of lithium. Potassium excretion did not change by acute lithium administration. The data presented indicate that prior to measurements of lithium clearance, lithium should be administered in the diet for 2 days, since acute lithium administration, intravenously or by gastric tube, causes great changes in renal tubular reabsorption.     

Sublingual administration of Delta9-tetrahydrocannabinol/beta-cyclodextrin complex increases the bioavailability of Delta9-tetrahydrocannabinol in rabbits

The bioavailability of Delta(9)-tetrahydrocannabinol (THC) was determined after its sublingual administration as solid THC/beta-cyclodextrin (THC/beta-CD) complex, and was compared to oral administration of ethanolic THC, in rabbits. The absolute bioavailability of THC after sublingual administration of solid THC/beta-CD complex powder (16.0 +/- 7.5%; mean +/- SD; n = 4) is higher than the bioavailability of THC after oral administration of ethanolic THC solution (1.3 +/- 1.4%; mean +/- SD; n = 4). The results suggest that sublingual administration of THC/beta-CD complex is a useful tool in improving absolute bioavailability of THC.     

Factors influencing the serum levels of cholesterol and beta-lipoproteins in starving rabbits]

The influence of starvation on the lipid metabolism was studied on male rabbits under usual conditions and in the presence of pyroxidine deficiency (4-deoxypyridoxine administration) and of thiamine (oxythiamine administration), and also in administration of neurotropic preparations (phenamine, seduxen). Starvation for 7 to 10 days led to increase of cholesterol and beta-lipoproteins level in the serum. Pyridoxine deficiency and phenamine administration caused a greater increase of cholesterol and especially or beta-lipoproteins. On the other hand, thiamine deficiency and seduxen administration limited an increase of cholesterol and beta-lipoproteins during hungry stress. Administration of aerovit for prophylactic purpose promoted a decrease of the metabolic shifts. The amount of cholesterol increased in the liver of hungry animals, especially after the phenamine administration and in the presence of pyridoxine deficiency; aerovit administration prevented increased cholesterol accumulation in the liver. The differences in the cholesterol level in the serum and and the liver can be explained by the changes of its biosynthesis during hungry stress.