Alterations in striatal neuropeptide Y system activity of rats with haloperidol-induced behavioral supersensitivity.

The study was conducted to determine whether the expression of behavioral supersensitivity induced by haloperidol (HAL) administered once daily (2 mg/kg i.p.) for 14 days is associated with the alterations in activity of neuropeptide Y (NPY) system in the striatum (caudate-putamen) and nucleus accumbens. Dopamine supersensitivity was tested by measurement of locomotor activity and stereotyped behavior after administration of the dopamine D2/D3 receptor agonist quinpirole (1 mg/kg i.p.) on day 1, 3 and 7 after HAL withdrawal. Neuropeptide Y-like immunoreactivity (NPY-LI) was determined in the striatum and nucleus accumbens isolated 6 h after quinpirole injection on day 1, 3 and 7 after the end of HAL treatment. NPY mRNA was quantified in these structures on day 7 after HAL withdrawal. HAL increased spontaneous locomotor activity and prevalence of rearing, grooming and head-down sniffing. At the same time, striatal NPY-LI increased progressively from the reduced level found on day 1 of haloperidol withdrawal. NPY mRNA remained unchanged. In saline-treated rats, quinpirole enhanced locomotion, rearing, and induced intense head-down sniffing and oral activity. These behavioral effects were accompanied by a decrease in striatal NPY-LI. NPY mRNA was slightly increased. HAL treatment altered response to quinpirole, namely it increased locomotion, intensified oral activity and reduced rearing and head-down sniffing. The second and the third quinpirole injection decreased NPY-LI levels. NPY mRNA was unchanged. In the nucleus accumbens, apart from a decrease in NPY-LI on day 1 after the last haloperidol dose, the level of NPY-LI and NPY mRNA in any experimental group did not differ from the control value. The presented results suggest that the alterations in the activity of the striatal but not nucleus accumbens NPY system contribute to adaptive changes induced by long-term haloperidol treatment and may be of significance to the motor hyperactivity induced by intermittent stimulation of postsynaptic dopamine D2 receptors.

Progress and dilemma of contemporary clinical pharmacology.

Owing to the great progress in clinical chemistry connected with utilization of applied mathematics, pharmacokinetics came into being. The unknown objective methods of research of drugs in human were discovered, among them controlled clinical trials (CCT). These new methodologies generated a new clinical discipline called clinical pharmacology (CPH) which has its roots in basic pharmacology but was applied in clinical specialties. This field is very young, recognized by World Health organization in 1970. Up to the 90s several enthusiasts developed quickly CPH. The scope and development of this discipline is presented in the first part of this article. At the end of the 20th century the science on drugs performed in humans was in the center of interest of the public as well as an object of great pressure of pharmaceutical industry, politicians, and the public. These phenomena started to influence CPH, practiced and taught in medical university faculties and patients care, unfavourably. Government, university authorities, non-profit organizations are not interested in supporting objective research in CPH on the highest academic level. The industry considers the mentioned studies as a threat for its profit. CCT was elaborated for objective comparison of effectiveness and efficacy of old (standard) drugs with the new approved substance. The main purpose of this type of study is a rejection of null hypothesis. Since 1990, these trials caused a strong movement toward evidence-based medicine. A few years ago trials were performed in independent academic centers. These studies were in experienced hands of the teams consistent of highly competent specialists of several fields of medicine. These centers contributed to the quality, intellectual rigor and impact of such clinical trials. But as economic pressure increases, this may belong to the past. Actually pharmaceutical companies curtailed the participation of academic centers in CCT to 40%. According to EU Parliament decision the pharmaceutical industry adopted the whole control of CCT. Politicians and society demand the instant application of new observations and discoveries into practice. Then new drugs approved in 2003 are mentioned. At the end, the general proposition to improve the Status of academic CPH and creditability of CCT is suggested: to develop essential studies on mechanisms of drugs on human being. The highest academic authorities, who understand the importance of CPH, have to discuss the necessity of funding of this type of research with university authorities, non-profit organizations and the Ministry of Health. To soften unavoidable conflict of interests, laborious discussions between academic scientists, pharmaceutic company authorities and governmental authorities are necessary. There is also an urgent necessity of new legislative acts. These proposals are very general and deficient. They were presented here to conclude this article on the present status of clinical pharmacology with the statement that the real threat for this discipline exists.

Flupentixol and trifluperidol reduce interleukin-1 beta and interleukin-2 release by rat mixed glial and microglial cell cultures.

Neuroleptics penetrate into the brain, where they act not only on neurons but probably also on glial cells. In the available literature, there are no reports on the effect of neuroleptics on cytokine release in glia cultures. The aim of this study was to evaluate the effect of neuroleptics on the release of proinflammatory cytokines (IL-1beta and IL-2) by mixed glial and microglial cell cultures. Trifluperidol at 20 and 2 muM reduced IL-beta secretion by mixed glial cultures after 3 days of exposure. Trifluperidol at 20, 2 and 0.2 muM diminished IL-beta secretion after 1 day of incubation. Trifluperidol at 20 and 2 muM reduced IL-2 release after 1 and 3 days of exposure. Flupentixol at 20 and 2 muM reduced IL-1beta by mixed glial cell cultures after 3 days of exposure. Flupentixol at 20, 2 and 0.2 muM caused diminution of IL-1beta release after 1 day of exposure. Flupentixol at 20 and 2 muM reduced IL-2 release after 1 day of incubation. Flupentixol at 20, 2 and 0.2 muM diminished IL-2 release after 3 days of exposure. Flupentixol at 20, 10, 2 and 0.2 muM reduced IL-1beta release by microgial cell cultures. Flupentixol at 20, 10 and 2 muM reduced release of IL-2 by microglial cells after 1 day of exposure. The results of the present study suggest that neuroleptics have an inhibiting effect on the release of glial cytokines, but clinical significance this results remains to be elucidated.

Effect of monthly atorvastatin treatment on hemostasis.

Apart from lowering lipid levels, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) produce many other favorable effects that contribute to their clinical efficacy in the primary and secondary prevention of cardiovascular diseases. The aim of this study was to assess the effect of 30-day atorvastatin treatment on major hemostatic risk factors (fibrinogen, PAI-1 levels, factor VII coagulant activity) in patients with primary hypercholesterolemia. We studied 18 hypercholesterolemic patients and 12 matched control subjects. Compared to the control subjects, hypercholesterolemic patients exhibited increased plasma PAI-1 levels and factor VII activity. Atorvastatin (20 mg/d) not only decreased total cholesterol, LDL cholesterol and oxidized LDL, but also reduced PAI-1 levels and factor VII activity and tended to decrease fibrinogen levels. The hemostatic effects of atorvastatin did not correlate with its lipid-lowering potential. Our study is the first to show that atorvastatin may exhibit a quick, beneficial and multidirectional nonlipid-related effect on hemostasis.

Increased striatal neuropeptide Y immunoreactivity and its modulation by deprenyl, clonidine and L-dopa in MPTP-treated mice.

The aim of this study was to evaluate the effect of MPTP (2 x 45 mg/kg s.c., 20 h apart) on striatal neuropeptide Y-like immunoreactivity (NPY-LI) in C57BL/6 mice. NPY-LI markedly increased 2 weeks after MPTP but it remained unchanged after 24 h, 1 or 6 weeks. The increase in NPY-LI was accompanied by depletion of dopamine (-80%), DOPAC (-70%), 3-MT (-44%) and HVA (-52%). L-Deprenyl completely prevented the MPTP-induced NPY-LI increase, neurodegeneration of the striatal dopamine system and motor dysfunction. Clonidine attenuated the neurotoxin effect on NPY-LI and dopaminergic neurons. L-dopa/carbidopa protected NPY neurons against MPTP but slightly enhanced MPTP-induced decrease in the levels of dopamine and its metabolites. The relationship between changes in NPY-LI and dopamine and serotonin metabolism determined by HPLC was discussed. The results further extend the range of MPTP-elicited modifications in striatum and demonstrate that drugs with antiparkinsonian activity can protect NPY neurons against MPTP toxicity.

Effects of fenofibrate and simvastatin on plasma sICAM-1 and MCP-1 concentrations in patients with hyperlipoproteinemia.

OBJECTIVE: The most important mechanism through which high plasma lipid levels trigger the formation of atherosclerotic lesions involves a change in the expression of adhesion molecules on endothelial and smooth muscle cells. The aim of this study was to evaluate an extralipid effect of fenofibrate and simvastatin by examination of MCP-1 and ICAM-1 plasma concentration after 1-month hypolipemic therapy as well as MCP-1 and ICAM-1 plasma concentration after 1-month therapy with low-fat diet alone. METHODS: Twenty patients with HLPIIb or HLPIIa, who did not respond to a low-fat diet, were treated with micronized fenofibrate or simvastatin, respectively, for 1 month. The control group included 18 normo-lipidemic, healthy age-matched participants; 10 patients with HLPIIa were effectively treated with a low-fat diet for 1 month. This group was compared to a control group of 10 healthy subjects. The plasma adhesion molecule levels were measured by an ELISA method before and after the treatment. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease. RESULTS: sICAM-1 levels were significantly higher in HLPIIa and HLPIIb patients (331 +/- 19 ng/ml and 423 +/- 23 ng/ml, respectively) compared with the control group (236 +/- 12 mg/ml). MCP-1 levels were also significantly higher in HLPIIa and HLPIIb patients (170 +/- 9 pg/ml and 183 +/- 15 pg/ml, respectively) compared with the control group (100 +/- 4 pg/ml). Fenofibrate (200 mg daily) significantly decreased sICAM-1 (by 17%) and MCP-1 levels (by 12.5%). Simvastatin (20 mg daily) caused a significant decrease (by 10.5%) in sICAM-1 levels only. Restriction in dietary lipids resulted in a significant decrease in the levels of cholesterol (8%), LDL cholesterol (14.9%) and ApoB (12.7%), which was accompanied by a significant decrease in the levels of sICAM-1 (8.7%) and MCP-1 (16.1%). CONCLUSION: The results of this study suggest that high lipid levels are accompanied by increased levels of sICAM-1 and MCP-1 and that hypolipidemic therapy only slightly decreases the levels of these molecules compared with plasma lipids. The hypolipidemic diet-related decrease in the levels of lipids, ICAM-1 and MCP-1 suggests that it is a drug-induced decrease in lipid levels but not a direct action of the drugs on endothelial cells, smooth muscle cells or macrophages that leads to a decrease in the levels of adhesion molecules.

Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia.

OBJECTIVE: Monocytes that migrate into the arterial wall participate in the development and, eventually, rupture of the atherosclerotic plaque. The aim of this study was to evaluate the secretion of monocyte chemoattractant protein-1 (MCP-1) by monocytes from hyperlipidemic patients treated with hypolipidemic drugs, namely fenofibrate, simvastatin, or atorvastatin to determine what role is played by these drugs in the development and stabilization of the atherosclerotic plaque. METHODS: Fifty-four hyperlipidemic patients, who did not respond to a low-fat diet, were treated with fenofibrate, simvastatin, or atorvastatin (18 patients in each group) for 1 month. The control group included 18 normolipidemic, healthy, age-matched participants. Ten hyperlipidemic patients were effectively treated with hypolipidemic diet alone for 1 month. This group was compared with a control group of ten healthy subjects. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease. Before and after treatment, monocytes were isolated from peripheral blood. After stimulation with lipopolysaccharide (LPS), MCP-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: MCP-1 levels were significantly higher in hyperlipidemic patients than controls: 15.8+/-0.47, 16.7+/-0.23, and 14.9+/-0.45 compared with 12.36+/-0.42 ng/ml. Fenofibrate, atorvastatin, and simvastatin significantly decreased MCP-1 levels from 15.8+/-0.47 to 8.79+/-0.89, from 16.7+/-0.23 to 7.46+/-0.73, and from 14.9+/-0.45 to 10.3+/-0.8 ng/ml, respectively. In the diet-treated group of hyperlipidemic patients, the level of MCP-1 before therapy was significantly higher than in controls (16.89+/-0.31 vs 12.45+/-0.36 ng/ml). The diet therapy caused a significant decrease in levels of MCP-1 to 15.1+/-0.36 ng/ml. There was a correlation between the decreased levels of lipids and the decreased release of MCP-1 in the patients treated with hypolipemic drugs. CONCLUSION: The drug-induced decrease in MCP-1 secretion in hyperlipidemic patients suggests that, apart from acting on lipids, the hypolipidemic drugs studied may directly inhibit the activity of monocytes.

Effects of haloperidol and clozapine on neuropeptide Y-like immunoreactivity in the nucleus accumbens and striatum of rats pretreated with psychostimulants.

It has been shown that the synthesis, release and levels of neuropeptide Y (NPY), a peptide linked to the dopamine system, are altered by stimulants with psychotomimetic properties and by antipsychotic drugs. This study was designed to evaluate the effect of 3-day haloperidol (HAL) (2 mg/kg i.p.) or clozapine (CLOZ) (25 mg/kg i.p.) treatment on neuropeptide Y-like immunoreactivity (NPY-LI) in nucleus accumbens and striatum (caudate-putamen) in rats pretreated with d-amphetamine or phencyclidine. D-amphetamine (5 mg/kg s.c. twice daily for 6 days and once on day 7) and phencyclidine (10 mg/kg i.p. once daily for 2 days and 15 mg/kg once on day 3) induced marked stereotypy with different symptomatology. Stereotypy is thought to resemble psychosis-related behavior. The first dose of either HAL or CLOZ was given 3 or 2h after the final d-amphetamine or phencyclidine injection, respectively. The control groups were injected with either saline alone, saline instead of psychostimulants, which was followed by antipsychotics, or psychostimulants followed by saline. Rats were sacrificed 24h after antipsychotics or 72 h after the last psychostimulant dose. Both psychostimulants similarly reduced nucleus accumbens and striatal NPY-LI. In saline-pretreated rats, HAL and CLOZ decreased nucleus accumbens NPY-LI, but only HAL decreased striatal NPY-LI. In both the structures examined the effects of HAL and d-amphetamine on NPY-LI were additive. HAL slightly enhanced but CLOZ reversed the phencyclidine-induced decrease in accumbens NPY-LI. The present study has shown that HAL and CLOZ produce different effects on nucleus accumbens and striatal NPY-LI in d-amphetamine or phencyclidine pretreated rats, and it suggests that these effects are related particularly to the dopaminergic and glutamatergic systems whose activities were altered by psychostimulants.

Plasma cytokines as predictors of coronary heart disease.

BACKGROUND AND OBJECTIVE: Growing body of evidence explicitly suggests the significant role of inflammatory processes in vascular diseases related to atherosclerosis. Monocytes, present in every phase of atherogenesis, are the principal cells accumulating in atherosclerotic plaque. Monocyte Chemotactic Protein 1 (MCP-1) seems to influence firm adherence of rolling monocytes and infiltration into the artery wall. Although the significant meaning of inflammation in atherogenesis has been proved, potential role of antiinflammatory cytokines remains unknown. Interleukin 10 (IL-10) is a major cytokine of pleiotropic antiinflammatory function known to exert inhibitory effects on monocytes. Recent data emerging from clinical and pathological studies suggest important role of thrombosis and fibrinolytic disorders in atherosclerosis complications especially in coronary heart disease (CHD). Individuals with greater Plasminogen Activator Inhibitor 1 (PAI-1) level are believed to be more susceptible to cardiovascular disease. METHODS: In our study we measured the plasma levels of MCP-1, IL-10 and PAI-1 in 10 patients with stable angina and 10 healthy subjects. We also estimated its mutual correlations. The plasma levels of MCP-1, IL-10 and PAI-1 were determined with R&D kits (ELISA). RESULTS: Plasma levels of MCP-1 were significantly higher (261.5+/-40.7 pg/mL vs 73.3+/-3.05 pg/mL; p<0.0002) and also levels of PAI-1 were higher (79.36+/-5.8 ng/mL vs 35.88+/-1.38 ng/mL; p<0.0001) in patients with SA compared with the healthy control subjects. Whereas plasma levels of IL-10 were lower (11.6+/-0.5 pg/mL vs 16.5+/-0.4 pg/mL; p<0.0001) compared with control group and correlated with both MCP-1 plasma level (r=-0.67; p<0.0015) and PAI-1 concentration (r=-0.69; p<0.0008). CONCLUSION: The data obtained confirm the predictive role of cytokines in patients with stable coronary heart disease. The negative correlation of anti-inflammatory IL-10 and PAI-1 was also found.

Neuroleptics normalize increased release of interleukin- 1 beta and tumor necrosis factor-alpha from monocytes in schizophrenia.

Some recent reports show that schizophrenia is accompanied by changes in lymphocyte activity. This study investigated the activity of monocytes by determining their release of interleukin- 1 beta (IL- 1 beta) and tumor necrosis factor-alpha (TNF-alpha). Monocytes were immunomagnetically isolated from the peripheral blood of schizophrenic patients before and after neuroleptic medication and stimulated by lipopolisaccharide (LPS) in vitro. The monocytes of schizophrenic patients released significantly higher amounts of IL- 1 beta and TNF-alpha than those of healthy controls. Treatment with the typical neuroleptics haloperidol and perazine decreased the release of IL- 1 beta and TNF-alpha to the control levels. The study has shown that the activity of monocytes is increased in schizophrenia and that neuroleptic treatment normalizes this activity.

Neuropeptide Y in obese women during treatment with adrenergic modulation drugs.

BACKGROUND: The aim of the study is the assessment whether weight loss treatment with adrenergic modulation drugs modifies neuropeptide Y (NPY) plasma concentration in obese women. MATERIAL AND METHODS: 13 obese women (BMI 38.3 +/- 4.4) were tested before and subsequently 10 and 20 days after weight loss treatment. The treatment consisted of a very low caloric diet of 400 kcal (1670 kJ) daily combined with ephedrine with caffeine (E + C) or ephedrine with caffeine and yohimbine (E + C + Y) administered for 10 days using the cross-over method. The patients underwent physical examination, including heart rate and blood pressure measurements, spectral heart rate variability (HRV) at rest and after 3 minute handgrip and a 15 minute cycloergometer exercise at 75 W. All the above mentioned tests were carried out thrice in each patient. In 13 obese patients and in 6 control women plasma NPY concentrations were determined by a specific radioimmunoassay using rabbit anti-NPY antiserum and a standard synthetic porcine NPY (Peninsula Lab.). RESULTS: Plasma NPY concentrations were significantly lower in the obese persons compared with the control group. During weight loss treatment with adrenergic modulation drugs no changes in plasma NPY were found at rest and after physical exercise. Also no differences in HRV indices were observed. CONCLUSIONS: 1. Low plasma NPY concentration observed in obesity may be a contraregulatory factor that could prevent further weight increase. 2. Weight reduction treatment did not affect plasma NPY concentration and cardiovascular response to physical exercise. 3. The doses of adrenergic modulation drugs used in our study did not induce any serious side effects, and were so low that no change of plasma NPY concentration and cardiovascular responses were observed at rest.

Levels of sICAM-1, sVCAM-1 and MCP-1 in patients with hyperlipoproteinemia IIa and -IIb.

OBJECTIVE: Hyperlipoproteinemia is one of the factors that are involved in the development of atherosclerosis. One of the mechanisms through which these high plasma lipid levels trigger the formation of atherosclerotic lesions is a change in the expression of adhesion molecules on endothelial and smooth muscle cells. The aim of this study was to evaluate the plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in patients with Type IIa (HLP-IIa) and IIb (HLP-IIb) hyperlipoproteinemias. SUBJECTS: Twenty patients with HLP-IIa, 20 patients with HLP-IIb and 23 control subjects were studied. To accurately evaluate adhesion molecule levels, we excluded those hyperlipemic patients and control subjects who had an inflammatory disease. METHODS: Plasma sICAM-1, sVCAM-1 and MCP-1 levels were measured by the ELISA method. RESULTS: sVCAM-1 levels in HLP-IIa and HLP-IIb patients (535 +/- 27 ng/ml and 545 +/- 22 ng/ml, respectively) did not differ significantly from those in the control group (558 +/- 20 ng/ml). sICAM-1 levels were significantly higher in patients with HLP-IIa and HLP-IIb (279 +/- 10 ng/ml and 322 +/- 12 ng/ml, respectively) compared to the control group (226 +/- 10 ng/ml). MCP-1 levels were significantly higher in HLP-IIa and HLP-IIb patients (151 +/- 12 pg/ml vs 154 +/- 12 pg/ml, respectively) compared to healthy controls (98 +/- 4 pg/ml). sICAM-1 levels in the HLP-IIb group were significantly higher than in the HLP-IIa group. CONCLUSION: The results of the study suggest that lipid abnormalities affect the levels of adhesion molecules and chemokines in plasma.

[The role of neuropeptide Y in anxiety]. / Rola neuropeptydu Y w leku.

Neuropeptide Y (NPY), one of the most abundant peptides in the mammalian brain, is implicated in the control of many physiological processes. It is also suggested the involvement of NPY in several neuropsychiatric illnesses. This review summarizes the present knowledge concerning the role of NPY in anxiety and discusses probable sites and receptors involved in the anxiolytic-like effect of NPY as well as interactions between the NPY and corticotropin-releasing factor (CRF) systems. The possible role of the NPY system in human psychopathological conditions associated with anxiety is also reviewed. Based on our data, we suggest that the NPY system is involved in antianxiety effects of diazepam and buspirone.

Effects of fibrates on plasma prothrombotic activity in patients with type IIb dyslipidemia.

OBJECTIVE: Increased levels of fibrinogen and plasminogen activator inhibitor 1 (PAI-1) are associated with an increased risk of ischemic coronary disease and its complications. Since atherogenic dyslipidemias are well-known risk factors for coronary heart disease, this study aimed to determine whether Type IIb dyslipidemia, one of the most atherogenic dyslipidemias, is accompanied by increased PAI-1 and fibrinogen synthesis. The additional aim of this study was to evaluate the effect of micronized fibrates on the levels of PAI-1 and fibrinogen in patients with Type IIb dyslipidemia. SUBJECTS: Thirty patients with Type IIb dyslipidemia and 12 age-matched control subjects were studied. Fourteen patients were treated with fenofibrate and 16 were treated with ciprofibrate for 1 month. METHODS: Plasma PAI-1 levels were measured by the ELISA method with Diagnostica Stago kit. The level of fibrinogen was measured by the Clauss method. RESULTS: PAI-1 levels in dyslipidemic patients before treatment differed significantly in both the fenofibrate and ciprofibrate treatment groups (101.18 +/- 36.47 ng/ml, 87.64 +/- 32.06 ng/ml, respectively) from those in the control group (32.32 +/- 7.39 ng/ml, p < 0.001). Compared with the control subjects (2.91 +/- 0.35 g/l), fibrinogen levels before treatment were higher in patients with dyslipidemia treated with ciprofibrate (3.42 +/- 0.59 g/l, NS) and fenofibrate (3.65 +/- 1.10 g/l, p < 0.05). One-month ciprofibrate treatment resulted in an insignificant decrease in PAI-1 levels (76.28 21.60 ng/ml, NS) and in a significant decrease in fibrinogen levels (2.73 +/- 0.40 g/l, p < 0.01). After one-month fenofibrate treatment PAI-1 levels (81.22 +/- 25.01 ng/ml, p < 0.01) and fibrinogen levels (2.95 0.72 g/l, p < 0.01) decreased significantly. CONCLUSION: Type IIb dyslipidemic patients have increased levels of PAI-1 and fibrinogen. Micronized fibrates decreased not only lipid levels but also the levels of fibrinogen and PAI-1 in these patients.

Recent insights into body weight control: from physiology to pathology.

Over the past several years, new modulators of feeding and body weight have been discovered, and our knowledge of the mechanisms and neurohumoral interactions between anorexigenic and orexigenic compounds has increased dramatically. This review aims to summarize the present knowledge of the role of leptin and several hypothalamic neuropeptides, such as neuropeptide Y (NPY), corticotropin-releasing hormone (CRH) and melanocortins, in the regulation of appetite and body weight. It also presents the progress made in the design of interactions between leptin and hypothalamic peptides in the regulation of feeding. The role of these compounds in the pathogenesis of obesity in animals and humans, and their potential usefulness in the treatment of this disorder, are discussed.

Effect of substituted benzamides on feeding and hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI) in rats.

The study was conducted: (i) to evaluate the effects of three substituted benzamides on feeding behaviour in rats with free access to food and in those with access to food limited either to the light or to the dark phase of the diurnal cycle; and (ii) to determine whether the hypothalamic neuropeptide Y (NPY) system is involved in the action of these drugs on feeding. In free-feeding rats, a single dose of eticlopride (1 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.) decreased 24-h food intake, whereas remoxipride (3 mg/kg, i.p.) produced no effect. Single doses of eticlopride and raclopride but not of remoxipride decreased hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI). Eticlopride administered once daily for 14 days decreased both food intake and hypothalamic NPY-LI. When given for 14 days, raclopride and remoxipride decreased food intake in rats with access to food in the dark (19.00-07.00) but not in thelight (07.00-19.00) phase of the diurnal cycle; both these compounds decreased hypothalamic NPY-LI only in the former group of rats. The results suggest that the effects of substituted benzamides on feeding behaviour depend on the drug and the time of administration and that these effects are related to the altered function of the hypothalamic NPY system.

A new immunological marker of atherosclerotic injury of arterial wall.

BACKGROUND AND OBJECTIVE: The atherosclerotic arterial injuries lead to many life threatening vascular incidents. It has been well documented that inflammatory processes play an important role in atherogenesis. Intensive studies are undertaken to find a serum marker of inflammatory reaction correlated with arterial injuries. METHODS: In our study we measured the level of interleukin-6 (IL-6) in patients with dyslipidemia IIa and IIb biochemically confirmed. Control estimations were done in age-matched group. Arterial injuries were evaluated as a thickening of complex intima-media in common carotid arteries by means of Doppler ultrasonography. RESULTS: Levels of IL-6 were significantly higher in both groups of patients with dyslipidemia as compared with the healthy control persons (IIa vs control p<0.001, IIb vs control p<0.001). The plasma level of IL-6 is significantly correlated to intima-media complex thickness (r=0.68, p<0.0001). CONCLUSION: We conclude that increase of serum concentration of IL-6 may be related to arterial wall injuries in the course of the most atherogenic lipid disorders.

Conditioned fear-induced changes in neuropeptide Y-like immunoreactivity in rats: the effect of diazepam and buspirone.

The study aimed to investigate the influence of conditioned fear, produced in the passive avoidance test, on neuropeptide Y-like immunoreactivity (NPY-LI) and the effect of anxiolytics on NPY-LI in frightened rats. Rats avoided the dark chamber, where they were previously subjected to electric footshock, and they exhibited increased numbers of defecations and gastric ulcers. Moreover, they showed increased NPY-LI in the amygdala, nucleus accumbens and hypothalamus, and decreased NPY-LI in the frontal cortex. Diazepam (1 or 3 mg/kg) and buspirone (1.5 or 5 mg/kg) dose-dependently inhibited passive avoidance and decreased the numbers of defecations, and they also decreased the number of gastric ulcers. Diazepam reversed while buspirone only attenuated the fear-induced changes in NPY-LI in all regions studied. In the amygdala, the effect of diazepam was dose-dependent. The effect of diazepam on both behaviour and NPY-LI was antagonized by flumazenil (15 mg/kg). Apart from supporting the role of the NPY system in fear and anxiety, the results of this study suggest that NPY is involved in the anxiolytic effects of diazepam and buspirone and that the effect of diazepam is mediated by benzodiazepine receptors.