Simvastatin decreases concentration of interleukin-2 in hypercholesterolemic patients after treatment for 12 weeks.

UNLABELLED: Statins, HMG-CoA reductase inhibitors are drugs with a potent lipid-lowering effect. They are also able to inhibit proliferation of smooth muscle cells, T-lymphocytes, to restore endothelial activity and to inhibit inflammatory responses. These effects have been called the pleiotropic effect of statins. Statins have demonstrated contrast to the inflammatory activity of macrophages. The aim of the study was to assess the influence of simvastatin on serum levels of proinflammatory cytokines such as IL-2 and TNFalpha in hypercholesterolemic patients. METHODS: In 58 non-smoking men with total cholesterol (TC) >7.8 mmol/L, LDL-cholesterol>5.5 mmol/L and fasting triglycerides<4.6 mmol/L serum IL-2 and TNFalpha were determined at the beginning of the study, after 3 months diet and after 3 months of simvastatin therapy (20 mg/day). The control group was composed of 10 healthy volunteers with correct lipid values: TC<5.2 mmol/L, LDL-cholesterol <2.3 mmol/L, HDL-cholesterol >1.5 mmol/L and triglycerides<2.3 mmol/L. RESULTS: There were significant reductions in IL-2 concentration after 3 months diet (p=0.0059) and significant (p=0.0003) decrease of IL-2 after 3 months of simvastatin therapy. Meanwhile we observed a significant decrease of TNFalpha concentration after 3 months diet (p=0.0001) and no significant decrease after 3 months of simvastatin therapy.

Circadian fluctuations of melatonin, tumor necrosis factor-alpha and its soluble receptors in the circulation of patients with advanced gastrointestinal cancer.

The objective of the study was to investigate the dynamic changes of melatonin (MLT), tumor necrosis factor alpha (TNFalpha), soluble TNFalpha receptors ( type I and type II) in serum of advanced cancer patients during 24 hours. The examined group consisted of 42 patients suffering from advanced gastrointestinal neoplasms (colorectal, gastric and pancreatic cancer). Blood samples were collected 6 times a day (8 a.m., 2 p.m., 6 p.m., 10 p.m., 2 a.m., and again 8 a.m.) as well as in healthy controls. Serum levels of TNFalpha and both its receptors were measured using ELISA type and the radioimmunoassay method was used to assess MLT levels. The circadian rhythm of MLT was altered because MLT reached its peak level at 8.50 a.m. with 5 hours delay in respect to average peak time in healthy humans. The presence of circadian rhythm of TNFalpha was proved (acrophase-1.40 a.m.), and no diurnal rhythm of soluble TNF receptors was observed. The concentration of soluble type I (p-55) receptor was distinctly lower than soluble type II (p-75). The peak of soluble type I receptor value appeared at 10.00 p.m. while the type II receptor reached its minimum level at the same time. Although there was no statistical correlation between the receptor concentrations, the shapes of both curves remained inversely proportional. The present results may suggest the presence of complex self-regulation mechanisms between the neuroendocrine system and the cytokine network in advanced gastrointestinal cancer patients.

[The effect of gamma-aminobutyric acid injected into lateral brain ventricle of rats after prenatal cadmium intoxication on flash visual evoked potentials (FVEP)]. / Wplyw kwasu gamma-aminomaslowego (GABA) podanego do komory bocznej mózgu szczurów po prenatalnej intoksykacji kadmem na odpowiedzi wzrokowych potencjalów wywolanych blyskami (FVEP).

PURPOSE: To find out any influence of gamma-aminobutyric acid (GABA) injected into lateral brain ventricle in newborn rats prenatally exposed to cadmium (Cd). METHOD: 18 white, Wistar, offspring rats were divided into 3 groups, each consisting of 6 rats (control, 5 ppm and 50 ppm of Cd in drinking water). Newborns were examined when they were 3-6 months old. FVEP were recorded before and after GABA injections. Two doses of GABA were used, 10 and 100 nmols. The statistic analysis with the test of t-Student was performed to estimate the amplitudes and latencies of the negative wave N1 and the next positive one P2. p < 0.05 was used to indicate significant difference. RESULTS: No significant changes in the latencies of peak N1 and P2 in the control and Cd 5 ppm groups (101-103%) after 10 nmols GABA were observed. However, the shortened (91-97%) of them was observed after both doses of GABA in Cd 50 ppm group. The mean value of amplitude of N1 in control rats increased to 127% after 10 nmols GABA and 142% after 100 nmols GABA. Moreover, the mean amplitude of P2 in this group increased to 108% and 146%, respectively. The high significant increase of the amplitudes of N1 (181-280%) and P2 (160-177%) waves were received after both doses of GABA in Cd groups. CONCLUSION: Cadmium increased the sensitivity of GABA-receptors in the OUN.

Influence of alternating low frequency magnetic fields on reactivity of central dopamine receptors in neonatal 6-hydroxydopamine treated rats.

The aim of this study was to evaluate the influence of extremely low frequency magnetic field (ELF MF) on the reactivity of the central dopamine D(1) receptor in rats with dopamine neurons chemically damaged by 6-hydroxydopamine (6-OHDA), an animal model of human's Parkinson's disease. The experiment was carried out on male Wistar rats. On day 3 of postnatal life, a lasting and selective chemical damage of the central dopamine system was induced in the rats by infusion of 6-OHDA HBr (133.4 microg intracerebroventricular, base form) given bilaterally into lateral ventricles of the brain. Control animals received similar treatments injecting only vehicle. At 2 months of age, both 6-OHDA treated and control rats were randomly divided into two groups. Rats from the first group were exposed to 10 Hz sinusoidal, 1.8-3.8 mT magnetic field one hour daily for 14 days. Rats of the second group were sham exposed, with the applicator solenoid turned off. On the day after the final exposure the evaluations were made of the rat's spontaneous irritability, oral activity, and catalepsy. The MF exposed rat with chemically induced dopamine neurons damage exhibited a reduction of irritability and oral activity when stimulated with SKF 38393 (the agonist of central dopamine D(1) receptor) and some increase of catalepsy after administration of SCH 23390(the antagonist of central dopamine D(1) receptor). These results indicate that ELF MF reduce the reactivity of central dopamine D(1) receptors in rats.

[Selenium plasma concentration level in children with food allergy]. / Ocena stezenia selenu w surowicy u dzieci z alergia pokarmowa.

Selenium (Se) is an essential component of many mammalian enzymes and therefore plays an important role in different metabolic processes. Se deficiency occurs in inadequate diet consumption as well as in some digestive tract and allergic diseases. In this research we showed that Se plasma concentration levels in healthy children was 71.8 mg/l, whereas in those with food allergy 54.1 mg/l (with smaller intestinal villus atrophy) or 50.4 mg/l (with greater intestinal villus atrophy). Obtained results indicate that children with food allergy display higher risk of Se deficiency. Antioxidative and immunomodulatory action of Se, connecting with promising literature data of Se supplementation, promote us to state, that this trace element could be used for accessory food allergies treatment.

Reversal of stress-induced memory changes by moclobemide: the role of neurotransmitters.

Studies on animals have shown that chronic stress is able to evoke behavioral changes such as locomotor activity deficit, decreased sleep, reduced food and water consumption and impaired memory. Chronic stress produces changes in concentrations of neurotransmitters, mainly in the hippocampus. The hippocampus is a vulnerable brain structure that is involved in learning and memory functions. In this study, we investigated the effects of chronic stress procedure and moclobemide in rats, and the influence of chronic stress on the levels of monoamines: noradrenaline (NE), dopamine (DA) and serotonin (5-HT) in the rat hippocampus [as well as their metabolites: dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA)]. It was found out that chronic 21-day stress caused worsening of memory: the well trained rats after stress procedure lost their ability to find food quickly. Because of many errors in finding the way, the time these animals needed was on average 2.4-times longer than that of the control group. Single, as well as prolonged (21 days) treatment with moclobemide (10 mg/kg/day) counteracted the deficit of memory induced by chronic stress. In stressed animals, we observed an increase in DA, decrease in DOPAC, 5-HT and 5-HIAA and decrease in NE levels. Moclobemide modulated the changes in the levels of neurotransmitters in the hippocampus, decreasing their turnover. The results demonstrate that moclobemide improves memory impaired by stress. They suggest also that moclobemide has a modulatory effect on stress-induced neurotransmitter changes which may be of importance for the protective effect of the drug with regard to memory impairment.

7-OH-DPAT, unlike quinpirole, does not prime a yawning response in rats.

Repeated treatment in ontogeny with the dopamine (DA) D(2)/D(3) receptor agonist quinpirole is associated with enhanced quinpirole-induced yawning and other behaviors such as vacuous chewing, vertical jumping, and antinociception. To determine if the reputedly DA D(3) agonist (+/-)-2-(dipropylamino)-7-hydroxy-1,2,3, 4-tetrahydronaphthalene (7-OH-DPAT) would prime for yawning in a manner analogous to that for quinpirole, rats were treated for the first 11 days after birth with an equimolar dose of either quinpirole or 7-OH-DPAT (195.4 nmol/kg/day) and tested for agonist-induced yawning in adulthood. While enhanced quinpirole-induced and 7-OH-DPAT-induced yawning was observed in quinpirole-primed rats, acute treatments with quinpirole and 7-OH-DPAT did not produce an enhanced yawing response in 7-OH-DPAT-"primed" rats. Our findings indicate that 7-OH-DPAT, unlike quinpirole, does not prime for quinpirole- or 7-OH-DPAT-induced yawning in rats.

[The effect of dopamine injected into the lateral brain ventricle on flash visual evoked potential (FVEP) after prenatal intoxication with cadmium]. / Wplyw dopaminy podawanej do komory bocznej mózgu szczurów na modulowanie odpowiedzi wzrokowych potencjalów wywolanych blyskami (FVEP) po prenatalnej intoksykacji kadmem.

PURPOSE: Earlier studies demonstrated that exposure, especially prenatal, of mammalians to cadmium (Cd) results in disorders of visual evoked potentials (FVEP). The purpose of this study is to find out any influence of cadmium intoxications on the effect of dopamine (DA) on FVEP. METHOD: 18 Wistar albino rats in 3-6 months of age were divided into 3 groups: control (drinking tap water only), prenatal exposure of 5 ppm, and 50 ppm Cd. Flash visual evoked potentials (FVEP) were recorded before and after injections of dopamine (DA) 100 and 200 nmols into the lateral brain ventricle. The amplitude and latency of N1 and P2 were statistically analysed by the test of t-Student. p < 0.05 was used to indicate significant difference. RESULTS: There were no statistical differences of mean latency of P2 waves between initial records of FVEP and after both doses of DA in all observed groups. The amplitudes of both waves increased after DA injections compared to initial values in all groups. The differences were statistically significant. The mean latencies of N1 peak were prolonged after both DA doses (106-109%) compared to the initial records (100%) in the control group; however, there were no changes of it in the Cd-treated groups before and after DA injections. CONCLUSION: Cadmium blocked the dopamine effect on the latencies of N1 and P2 of FVEP (because it prolonged them alone); however, cadmium increased the stimulative effect of dopamine on their amplitudes.

Nitro-l-arginine attenuates SKF 38393-induced oral activity in neonatal 6-hydroxydopamine-lesioned rats.

Nitric oxide (NO) in brain has been implicated in neuronal regulatory processes and in neuropathologies. Previously we showed that NO modified quinpirole-induced yawning, a behavioral measure of dopamine (DA) D3 receptor activation in rats. The aim of this study was to characterize the effect of nitro-L-arginine methyl ester HCl (NAME) and L-arginine HCl on reactivity of rats to the DA D1 receptor agonist SKF 38393 and DA D1 antagonist SCH 23390 in intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (134 micrograms of base ICV at 3rd day after birth). L-arginine HCl (300 mg/kg i.p.) increased the oral activity response in 6-OHDA-lesioned rats, like SKF 38393, and induced catalepsy in intact control rats, like SCH 23390. In contrast, NAME had no effect on oral activity or catalepsy, but fully attenuated SKF 38393-induced oral activity. These findings indicate that L-arginine HCl has no apparent effect at the DA D1 receptor, but that NAME is effective in attenuating a DA D1 agonist-induced effect. Consequently NO may be an intracellular second messenger for supersensitized receptors associated with DA D1 agonist-induced oral activity.

Nitric oxide (NO) and central dopamine (DA) D3 receptor reactivity to quinpirole in rats.

Nitric oxide (NO) has been implicated in large number of pathologies and in normal physiological function of the brain. The aim of this study was to recognize the effect of Nitro-L-Arginine Methyl Ester.HCl (NAME) and L-Arginine Ethyl Ester.HCl (ARGININE) on reactivity of the central DA D3 receptor to agonist (Quinpirole) in rats. For this reason we have been used specific behavioural procedure such yawning behaviour which is mediated via central DA D3 receptors. Experiments were perform in adult male Wistar rats treated daily with quinpirole (0.05 mg/kg IP) or vehicle (0.9% NaCl) for the first 11 days from birth to obtain of the central D3 receptor supersensitivity. NAME and ARGININE in different way modified response of the central DA receptor to quinpirole estimated by means yawning behavioural procedure.

Prenatal ethanol diminishes reactivity of presumed dopamine D3 receptors in rats.

Ethanol abuse in pregnancy is known to produce serious damage to the developing central nervous system of mammalian species. As with several other classes of nerves, the ontogenetic influence of ethanol on dopamine (DA) nerves is long-lived. To test whether reactivity of DA receptors might be altered by prenatal ethanol administration, rats were given 10% (v/v) ethanol in their drinking water, starting 10 days before mating and continuing to the end of pregnancy. Male offspring were tested at 3 months for behavioral effects known to be induced by DA agonists acting at specific subtypes of DA receptors. The oral activity dose-effect curve for SKF 38393, a DA D1 agonist, was not altered from control. However, quinpirole-induced yawning behavior, reputedly a DA D3-associated event, was markedly impaired in the male rats that had been exposed in utero to ethanol. These findings indicate that prenatal ethanol exposure may predominately produce diminished reactivity of the DA D3, but not DA D1 subtype of DA receptor.

Ethanol inhibits cadmium accumulation in brains of offspring of pregnant rats that consume cadmium.

The present study was designed to test the effect of ethanol on cadmium accumulation in tissues of pregnant rats and their offspring. Starting 10 days before mating and continuing until parturition, ethanol (10% v/v) was present in the drinking water of half the rats. Cadmium chloride (CdCl2; 50 ppm) was present in the water of half the rats (+/- ethanol) from the fist day after mating until parturition. On the day of parturition cadmium accumulated to a moderate level in bone (7.3 micrograms/g tissue, wet weight; this and other values, P < 0.05 vs. control), liver (12.9 micrograms/g) and kidney (13.0 micrograms/g) of dams, while the brain had only a low level of cadmium (0.45 microgram/g). In offspring at 6 weeks cadmium accumulated in high amounts in the brain (34.0 micrograms/g), bone (15.9 micrograms), kidney (78.2 micrograms/g) and particularly the liver (227.3 micrograms/g). Ethanol, given simultaneously with cadmium, inhibited cadmium accumulation in brain (1.8 micrograms/g), bone (3.28 micrograms/g) and kidney (61.3 micrograms/g), but enhanced cadmium accumulation in liver (408.7 micrograms/g). At 12 weeks there were only residual levels of cadmium in all tissues of offspring. These findings demonstrate an interaction between 2 known teratogenic agents, with ethanol conferring protection of the brain from cadmium accumulation. The nature of this interaction is not known, but is likely to be related to ethanol induction of metallothionein in the liver and placenta.

[Diazepam (Relanium)--current views on its action with special reference to developmental age]. / Diazepam (Relanium)--wspólczesne poglady na dzialanie, ze szczególnym uwzglednieniem okresu rozwojowego.

In a survey of the pertinent literature the pharmacological and toxicodynamic, effects, metabolism and mechanism of action of diazepam in experimental animals and humans are discussed. Particular attention is paid to the effects of diazepam given during the developmental age on the development and function of the central nervous system in mammals.

[Ethanol: current theories on its toxic effect with special reference to the effect on the central nervous system of adult mammals and during individual development]. / Etanol: wspólczesne poglady na dzialanie toksyczne ze szczególnym uwzglednieniem wplywu na osrodkowy uklad nerwowy ssakow doroslych i w okresie rozwoju osobniczego.

Present-day views on the molecular mechanism of ethanol action upon the central nervous system of adult mammals as well as consequences of the brain exposure to ethanol during fetal life, and upon the development and function of this organ in postnatal life are reviewed. Mechanisms of teratogenic effect of ethanol are also discussed.

Effect of ethanol and diazepam given to pregnant rats on the behavior and catecholamine content in the brain of offspring.

Effect of separate and combined treatment with ethanol and diazepam applied to pregnant rats upon the behavior of 3- and 6-week old and 3 month old rats, as well as on the content of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in various brain areas was investigated. It has been shown that separate application of ethanol and diazepam causes slight changes in the behavior and content of amines on the brain of offsprings. Combined application of ethanol and diazepam to pregnant rats exerts marked effects upon the behavior of offsprings and causes a decreased content mainly of 5-HT and 5-HIAA in the investigated areas of the brain.

Basic pharmacological properties of a novel antiinflammatory drug tryptamide.

In rats and mice the basic pharmacological properties of tryptamide (TRP), a novel antiinflammatory substance were studied. The LD50 doses were for male rats 1260 mg/kg ip or 8.5 g/kg po, for male mice: 1980 mg/kg ip or 9.3 g/kg po. TRP produced evident antiinflammatory effects of potency comparable with those of phenylbutazone when studied by means of carrageenin-induced rat paw oedema and prostaglandin synthetase activity in vitro. TRP reversed pyrogen-induced hyperthermia in rats, elicited analgesic effects in rats, but not in mice, prolonged the time of hexobarbital sleep in rats and inhibited locomotor activity in rats and mice. TRP has not elicited side effects on the circulatory system of rats and cats. It is concluded that TRP may undergo clinical trials as a potential antiinflammatory drug. During these trials the attention should be paid to possible central side effects the drug.

Free amino acids in cytosol of rat brain after intraventricular administration of 5,6-dihydroxytryptamine and 6-hydroxydopamine.

Levels of 24 free amino acids were estimated in the brain after administration of 5,6-dihydroxytryptamine and 6-hydroxydopamine into the lateral brain ventricles of male Wistar rats. These neurotransmitters caused serotoninectomy and sympathectomy in the diencephalon, striatum, brain stem and medulla, thalamus and hypothalamus, cerebral cortex and cerebellum. The most abundant amino acids in these brain structures were: glutamic acid, serine, aspartic acid, cystine, gamma-aminobutyric acid, glycine, tryptophan and alanine. We detected and quantified changes in the levels of these and other amino acids in the investigated regions of the rat central nervous system, under the influence of these two neurotransmitters.

Behavior of rats during one-year administration of fluphenazine and subsequent withdrawal period.

During one-year administration of fluphenazine [FLU], 1 or 5 mg/kg/d ip. two phases in the behavior of rats were observed. During the first four months of treatment the locomotor and exploratory activities were depressed, while during the following months the reversal of this phenomenon was observed, and the activity of FLU-treated rats increased, particularly in the open-field test. The irritability of rats showed a triphasic change during one year treatment with 5 mg/kg/d FLU. Catalepsy declined with the increase in length of treatment and dose of FLU during the first three months of experiment. During the first 2 weeks of FLU withdrawal the locomotor and exploratory activities and irritability of rats increased. The behavioral differences between controls and FLU-pretreated rats were observed between the 6th and 8th day of withdrawal period. The results demonstrated the occurrence of multiphasic changes in the behavior of rats during one year administration of FLU and after its withdrawal. They warrant further studies on the central nervous system reactivity during a prolonged neuroleptic therapy and after its cessation in man.