Analysis of in-hospital analgesic pharmacotherapy costs and regimen and impact on postoperative pain-related function in degenerative lumbar intervertebral disc disease.

BACKGROUND: Pain medication may affect clinical and economic outcomes, and a detailed description of pain medication use is advocated in the literautre for better assessment of clinical outcomes of spine surgery, which otherwise clould be misleading. OBJECTIVES: To analyze the impact of in-hospital analgesic pharmacotherapy after spine surgery on subjective quality of life and pain relief in patients with degenerative lumbar intervertebral disc disease (DLIVD), and also to analyze pharmacotherapy costs. DESIGN: A single-center study included 50 patients with L5/S1 or L4/L5 DLIVD, eligible for spine surgery. INTERVENTION: Neurosurgery for DLIVD. MAIN ENDPOINTS: Outcomes in terms of postoperative pain and function were recorded prospectively using standardized questionnaires. Data for cost analysis and pharmcotherapy regimen were obtained retrospectively from case histories, doctors' request cards and hospital discharge summaries. RESULTS: Mean total pharmacotherapy cost amounted to €453.42±49.09. Mean pharmacotherapy cost amounted to €314.76±54.21 preoperatively, and €138.66±25.54 postoperatively. The greatest improvement in function and quality of life was in patients treated with non-opioids. CONCLUSION: This study supports the notion that analgesic pharmacotherapies could be differentiated in terms of overall impact on quality of life, and that pain-related distress might be the most relevant factor in this setting.

Angiotensin 1-7 formation in breast tissue is attenuated in breast cancer - a study on the metabolism of angiotensinogen in breast cancer cell lines.

The tissue renin-angiotensin system (RAS) plays an important role in the development and progression of many diseases. It has been confirmed that angiotensin II (ANG II) participates in the proliferation and angiogenesis of breast cancer. Moreover, some RAS dysregulations in cancer have been observed. Recent studies on the role of two opposite axes of angiotensinogen metabolism - ACE (angiotensin-converting enzyme)/ANGII/AT1R (angiotensin receptor type 1) and ACE-2/ANG 1-7/MAS (mitochondrial assembly) - indicate their importance in tumor growth and invasion, but studies describing the metabolic pathways in breast cancer and the role of newer angiotensins, such as ANG 1-12, remain lacking. In this study, the metabolism of angiotensinogen fragments in three breast cancer lines, namely, MDA-MB-231, MCF-7, and T-47D, compared with normal breast tissue cells (PCS-600) was estimated. Incubation of the cancer cells with angiotensinogen resulted in the prevalent formation of ANG 1-7. A difference in the ability to form ANG II was observed between cell lines. In normal breast cells, the strong predominance of the ACE-2/ANG 1-7/MAS pathway was detected. In cancer cells, differences in angiotensinogen metabolism depending on cancer line were observed; the prevalence of the ACE/ANG II/AT1R pathway was shown. Expressions of the RAS component were dysregulated in cancer cells and differed between cell lines. In conclusion, the ability of breast cancer cells to produce numerous angiotensin peptide metabolites was demonstrated. The metabolism of angiotensinogen differed between various types of breast cancer cells. The obtained results indicate the greater importance of the classical pathway - ACE/ANG II/AT1R - in breast cancer cells. The production of ANG 1-12 seems to be marginal in breast tissue, but a tendency for the higher formation of this peptide in cancer cells was observed. The production of ANG 1-7 was significantly lower in cancer cells, whereas the expression of MAS receptor was higher than that in the control. This finding suggests that substances with MAS receptor agonist activity could be useful in the treatment of breast cancer, but this requires further investigations.

Differential effects of nitric oxide deficiency on primary tumour growth, pulmonary metastasis and prostacyclin/thromboxane A2 balance in orthotopic and intravenous murine models of 4T1 breast cancer.

The role of nitric oxide (NO) in tumour progression and metastasis is not clear, therefore the present work aimed to better characterise the effects of nitric oxide synthase (NOS) inhibition by L-Nω-nitroarginine methyl ester (L-NAME) on primary tumour growth, pulmonary metastasis, inflammatory state and prostacyclin (PGI2)/thromboxane A2 (TXA2) balance in a 4T1 murine model of breast cancer. To distinguish effects of NO deficiency on disease development, 4T1 cancer cells were administered orthotopically or intravenously to Balb/c mice. The systemic NO bioavailability, pulmonary inflammation and plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were assessed. The study shows that, in the orthotopic model of 4T1 breast cancer, L-NAME hampered primary tumour growth, reduced pulmonary metastases, delayed inflammatory response but did not alter biosynthesis of TXB2 and 6-keto-PGF1α as well as PGI2/TXA2 ratio in cancer-bearing mice. Interestingly, in the intravenous model of 4T1 breast cancer, NOS inhibition did not influence metastasis nor inflammation, but it increased both TXB2 and 6-keto-PGF1α biosynthesis without affecting PGI2/TXA2 ratio. In conclusion, in a 4T1 murine model of metastatic breast cancer, NO plays a major role in primary tumour development, while NO is not the key mediator of cancer cell extravasation to the lungs. Furthermore, NO-deficiency activates a PGI2-dependent compensatory mechanism only in the intravenous model of 4T1 breast cancer.

The antiatherogenic effect of new biocompatible cationically modified polysaccharides: chitosan and pullulan - the comparison study.

Pullulan and chitosan are biocompatible polysaccharides obtained from natural sources with many biomedical applications. Cationically modified polymers, such as chitosan and pullulan after covalent attachment of glycidyltrimethylammonium chloride (GTMAC), showed beneficial biological properties. In the present study, it was clearly demonstrated and confirmed that both cationically modified polysaccharides (chitosan-GTMAC and pullulan-GTMAC) have the antiatherosclerotic potential by inhibition of atherosclerotic plaque development and controlling the expression of genes involved in lipid metabolism. It has also been shown that the cationically modified chitosan (HTCC) at a dose of 200 mg/kg b.w./day in male apoE-knockout mice acted as hypolipidaemic agent. It was observed that a statistically significant decrease in low-density lipoprotein (LDL) cholesterol level by 32% occurred under the influence of HTCC at a dose of 200 mg/kg b.w./day after 16 weeks of the experiment compared to the control group of apoE(-/-) mice. Moreover, under the influence of cationically modified chitosan administered orally to female apoE-knockout mice at a dose of 300 mg/kg b.w./day for 18 weeks a statistically significant reduction by 33% in the area of atherosclerotic plaque was observed compared to the control group, i.e., apoE-knockout mice whose diet was not supplemented with the cationically modified polysaccharide. Current in vivo studies connected with cationically modified pullulan showed a statistically significant 22% reduction of the area of atherosclerotic plaque in the apoE(-/-) mice fed with a feed containing Pull-GTMAC at a dose of 500 mg/kg b.w./day for 18 weeks in comparison to the control group of apoE-knockout mice. In the in vitro studies it was also shown that cationically modified chitosan acted therapeutically by reduction of the level of the expression of human 3-hydroxy-3-methylglutaryl-CoA reductase (human HMG-CoAR) after 24 hours of incubation with HepG2 cells. However, cationically modified pullulan did not show this effect in the experiment on HepG2 cell line. On the other hand, Pull-GTMAC caused a statistically significant increase in insulin induced gene 1 (INSIG1) expression and increase in mRNA level of LDL receptor in brown fat tissue of female apoE-knockout mice after oral administration with feed at a dose of 300 mg/kg b.w./day for 18 weeks in comparison to the control group of apoE(-/-) mice, that was crearly demonstrated the effect of cationically modified pullulan on the expression of lipid metabolism genes in in vivo conditions. In the present article we have shown for first time that cationically modified pullulan and chitosan have some similarities in their antiatherogenic action but there are also some minor differences in mechanism of their effect on lipid metabolism.

The influence of aripiprazole and venlafaxine on the antidepressant-like effect observed in prenatally stressed rats (animal model of depression).

Depression is a nosological entity which may appear alone or concomitantly (e.g. in schizophrenia). Analysis of data from both clinical and experimental studies allows a conclusion that atypical antipsychotics, such as aripiprazole (ARI), may also be effective in treating depression in addition to antidepressants. The aim of the studies was to determine antidepressant efficacy of ARI, venlafaxine (VEN) and combined therapy using both drugs, in prenatally stressed rats (animal depression model) and control group. In addition, this article was aimed at determining the effect of these drugs on locomotor activity of these animals. The effect of chronic stress used in pregnant rats and the use of drugs such as ARI (1.5 mg/kg) and VEN (20 mg/kg) were studied in forced swimming test (FST; antidepressant effect) and locomotor activity test. Performed tests confirmed the antidepressant effect of ARI, VEN and efficacy of combined drugs in FST in both prenatally stressed rats (effect present upon single administration and after 7, 14 and 21 days of testing) and control group rats (effect present upon single administration and 7 days of testing). Moreover, upon single administration of the used drugs to prenatally stressed rats, it was found sedative effect - reduced animals' locomotor activity. Study results have proven antidepressant and sedative efficacy of ARI, VEN and combined administration of these drugs. Due to the small amount of data on the above preparations, in particular in the context of animal depression models, further studies in this respect are recommended.

Genetic Characterization of Porcine Circovirus Type 2 (PCV2) in Pigs of Bhutan.

Porcine circovirus (PCV) is a small non-enveloped virus with a single-stranded circular DNA with two antigenically and genetically different species, PCV1 and PCV2. Among these two, PCV2 is responsible for multifactorial disease syndromes, the most important disease known as PCV2-systemic disease (PCV2-SD), previously known as post-weaning multisystemic wasting syndrome (PMWS). The epidemiological situation is dynamically changing and new strains including recombinant PCV2 have emerged in Asia. In Bhutan, pigs are important livestock and play a very important role in providing meat and income for rural farmers. Although high rate of pigs seropositive against PCV2 was described in Bhutan, there was no virological evidence for PCV2 infections. This study was conducted to confirm the presence of PCV2 through detection of PCV2 DNA and molecular characterization of PCV2 strains in tissue and blood samples collected from Bhutanese pigs. Porcine circovirus type 2 genome was detected in 16 of 34 tissue samples pigs from the government farm. In 9 pigs, very high level of viral replication indicated that PCV2-SD was detected. Phylogenetic analysis performed with a set of GenBank sequences revealed that the Bhutanese PCV2 strains belonged to the PCV2b genotype and grouped with cluster 1C.

New cationically modified pullulan attenuates atherogenesis and influences lipid metabolism in apoE-knockout mice.

Pullulan is a biocompatible polysaccharide obtained from black, yeast-like fungus Aureobasidium pullulans. This polymer is used to deliver various substances to the liver because of its specificity for this organ. Pullulan is internalized into hepatocytes in the process of asialoglycoprotein receptor mediated endocytosis. Recently, by reaction with glycidyltrimethylammonium chloride (GTMAC) we have successfully synthesized a cationically-modified pullulan (Pull-GTMAC). Pull-GTMAC exhibits some unique beneficial effects not found for its native counterpart. In this article we have reported for the first time that Pull-GTMAC administered orally to apoE-knockout mice (murine model of atherosclerosis) at a dose of 300 mg/kg b.w./day for 18 weeks showed anti-atherosclerotic activity reducing the area of atherosclerotic plaque. We have also found that Pull-GTMAC at a dose of 300 mg/kg b.w./day increases both the average daily mass of feces and the average number of droppings excreted by apoE(-/-) mouse in relation to the control sample derived from the mice fed with feed without the tested compound. However, the raw fat content in the feces of apoE-knockout mice was decreased in the group fed with the diet containing Pull-GTMAC towards control group of animals. Pull-GTMAC caused also statistically significant increase of mRNA level for LDL receptor in the apoE(-/-) mice liver after administration at a dose of 300 mg/kg/b.w./day for 18 weeks. However, the compound had no impact on lipid profile in serum of the tested mice. What is more, the studies on HepG2 cell line indicated an antiproliferative potential of cationically modified pullulan after 24 hour and 48 hour of incubation with the polysaccharide. In this paper we have shown for first time that cationically modified pullulan has antiatherogenic potential and influences on lipid metabolism.

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

OBJECTIVES: The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. METHODS: The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. RESULTS: Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. CONCLUSION: Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness.

Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography.

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.

Neuroleptics and enrichment environment treatment in memory disorders and other central nervous system function observed in prenatally stressed rats.

It is believed that the most effective method of treatment in schizophrenia is pharmacotherapy, in particular, the use of atypical neuroleptics like aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have shown that enriched living conditions and tobacco smoke exposure can also affect the cognitive functions that are disturbed in the course of schizophrenia. The aim of the study was to find whether tobacco smoke and enrichment living conditions have the influence on cognitive functions in the newborn offspring of prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment modify those functions (Morris water maze). The study (in the same conditions) also analyses immobility time (Porsolt test) and motor activity of animals that received ARI and OLA. It has been shown that ARI and OLA as well as enriched environment reduce cognitive function disorders and modify cognitive functions in rats exposed to tobacco smoke. In turn, current research has shown that nicotine has increased cognitive function disorders compared to the previous study (animals without tobacco smoke exposure).

Significant deterioration of anti-atherogenic efficacy of nebivolol in a double (apolipoprotein E and endothelial nitric oxide synthase) knockout mouse model of atherosclerosis in comparison to single (apolipoprotein E) knockout model.

Anti-atherogenic action of nebivolol in apolipoprotein E (apoE)-single knockout mouse model can be explained by its beneficial effect on endothelium, especially on endothelial nitric oxide synthase (eNOS). We, therefore, decided to use apoE and eNOS-double knockout mouse model to confirm that mechanism of nebivolol beneficial action. In apoE-single knockout mice, lesion area measured by "cross-section" of aortic roots was 79,244 ± 6,143 µm(2) in the control group versus 65,347 ± 6,152 µm(2) in nebivolol-treated group (P<0.05). However, in apoE and eNOS-double knockout mice, lesion area measured by "cross-section" of aortic roots was 92,319 ± 8,876 µm(2) in the control group versus 98,609 ± 9,164 µm(2) in nebivolol-treated group (P>0.05). The comparison between apoE-single knockout mice and apoE & eNOS-double knockout mice without treatment also showed statistically significant difference: 81,232 ± 8,264 µm(2) versus 92,319 ± 8,876 µm(2) (P<0.05). This is the first report that describes the effect of nebivolol on atherogenesis in apoE and eNOS-double knockout mice, proving directly the necessity of the presence of eNOS in endothelium for nebivolol to show its an anti-atherogenic potency.

The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin I metabolism in aorta of apoE-knockout mice.

The detrimental role of over activation of renin-angiotensin system (RAS) in atherogenesis is widely recognized. Recently, we have demonstrated that Ang-(1-7) peptidomimetic - AVE0991, as well as known beta-adrenolytic agent nebivolol, exert anti-atherogenic actions in mouse model of atherosclerosis - apoE-knockout mice. Here, using LC-ESI-MS ex vivo system, we tested whether prolonged treatment of apoE-knockout mice by these drugs can influence RAS in aorta of apoE-knockout mice in regard to generation of most active metabolites of Ang I-Ang II and Ang-(1-7). As compared to wild type animals there was increased generation of Ang II in aorta of apoE-knockout mice, while the formation of Ang-(1-7) did not differ between both groups. Either treatment with AVE0991 or nebivolol resulted in significant attenuation of Ang II production in aorta of apoE-knockout mice. In conclusion, for the first time we directly demonstrated that there is increase in ability of aortic tissue to generate Ang II in mouse model of atherosclerosis of apoE knockout mice, and that such effect could be efficiently attenuated either by treatment of nebivolol or Ang-(1-7) peptidomimetic - AVE0991. The exact mechanism(s) responsible for interference of both drugs with RAS require further investigation.

The effect of ethyl alcohol on the function of spatial memory in rats.

Alcoholism is a mental disease in the course of which depression, anxiety, and cognitive function deficits may appear, and these symptoms can be aggravated by comorbid schizophrenia.The aim of this study was to find whether spatial memory (Morris Water Maze) function impairment is found in prenatally stressed rats (PSG) (prenatal stress paradigm - animal model of schizophrenia) and whether aripiprazole ARI and olanzapine OLA modify these functions. It was also important to study the effect of ethyl alcohol administered to rats.Behavioural tests showed that ARI and OLA improved spatial memory in the non-stressed control group (NSCG) and in the PSG. Moreover, spatial memory in the non-stressed alcohol group (NSAG) improved significantly compared to the NSCG, while in the prenatally stressed alcohol group (PSAG) spatial memory improved both in comparison to the NSCG and PSG. No statistically significant differences were found by comparing groups which received ethyl alcohol (NSAG, PSAG).

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice.

Our interest focused on an open question whether AT-(1-7), nonpeptide receptor agonist: AVE 0991, is able to ameliorate atherosclerosis. We used an apolipoprotein E (apoE) - knockout mice model of atherosclerosis. Experimental groups received the same diet as control, mixed with: AVE 0991 at a dose of 0.58 µmol/kg b.w./day, perindopril at a dose of 0.4 mg/kg b.w./day or with tiorphan at a dose of 2.5 mg/kg b.w./day. A-779 [(D-alanine)-angiotensin (1-7)] was given at a dose of 3.3 mg/kg b.w., 3 times a week i.p. Measured by "en face" method, the percentage of occupied by Sudan IV-stained surfaces were as follows: 14.2±1.9 % in control group, whereas in AVE 0991-treated as well as in perindopril-treated groups percentages were statistically significantly lower. In tiorphan group there was no change comparing to control group, whereas in A-779 group percentage was statistically significantly higher. "Cross-section" of aortic roots revealed also the difference in atherosclerotic lesions. The mean surfaces, occupied by oil red O-stained changes were: 91.213±8.123 µm(2) in control group, while in AVE 0991-treated as well as in perindopril-treated groups lesions were statistically significantly lower. In tiorphan group there was no change; however, in A-779 group lesions were statistically significantly higher. Measured by real time RT-PCR relative p22phox (submit of NADPH oxidase) expression was significantly decreased in AVE 0991-treated mice. As revealed by flow cytometry, the expression of co-stimulatory molecules: CD86, CD80 and CD40 on both dendritic cells (CD11c+) and macrophages (F4/80+) was reduced in AVE 0991-treated group, which correlated with decreased expression of CD69 activation marker on CD4+T cells. In our report we showed the beneficial effect of AVE 0991 on atherogenesis in gene-targeted mice.

Evaluation of the knowledge of primary healthcare patients in Poland on the prevention of hypertension: a community study.

OBJECTIVES: To investigate the knowledge of Poles on the prevention of arterial hypertension (HT) and identify the main souces of knowledge in order to make health promotion activities more effective, and thus increase the efficiency and efficacy of the Polish healthcare system. STUDY DESIGN: Community study. METHODS: This questionnaire study included 180 subjects (120 primary healthcare patients without a history of diagnosed HT and 60 primary care physicians). RESULTS: The knowledge of most surveyed patients was insufficient (43%, n = 52) or sufficient (40%, n = 48) for the effective prevention of HT; 17% (n = 20) of the respondents had knowledge that was definitely sufficient, and none of the respondents had knowledge that was definitely insufficient. The patients reported that primary care physicians were the most common source of health information (67%, n = 80). Primary care physicians were also the most trusted source of information. CONCLUSIONS: Patients' knowledge on smoking, diet and exercise is sufficient for the effective prevention of HT. The areas of insufficient knowledge for the development of HT and possible organ complications are drinking alcohol, stress, genetic factors and diabetes.

The effect of doxycycline on atherogenesis in apoE-knockout mice.

Doxycycline at subantimicrobial doses inhibits matrix metalloproteinases (MMPs) activity, and is the only MMP inhibitor which is widely available in clinical practice. The aim of the study was to reveal whether non-specific MMPs inhibition by tetracycline could ameliorate development of atherosclerosis in apolipoprotein E (apoE)-knockout mice. Doxycycline (1.5 mg/ kg b.w./day) administered orally attenuated atherogenesis, measured both by "en face" method (10.25±1.7% vs. 15.7±2.0%, p<0.05) and "cross-section" method (66,254±7,468 µm(2) vs. 90,687±8,521 µm(2), p<0.05). In-situ zymography showed decrease of the extent of non-specific gelatinase activity in doxycycline-treated mice This is the first report to date describing the effect of doxycycline on atherogenesis in apoE-targeted mice.

Effect of venlafaxine and nicotine on the level of neurotransmitters and their metabolites in rat brains.

Nicotine (NIC) and venlafaxine (VEN) have been proved to exert antidepressant activity in both human and animals. The effect of antidepressant doses of NIC and VEN (our previous results) on noradrenergic (NA), dopaminergic (DA), serotoninergic (5-HT) neurotransmitters and their metabolites: DOPAC, HVA and 5-HIAA in rats' hippocampus in freely moving rats were determined by microdialysis technique and HPLC method. Both drugs release 5-HT and NA, but VEN to a greater degree. DA level was affected only by VEN, however NIC extended the response of the DA system on VEN's effect. Combined administration of drugs caused the greatest changes in the 5-HT system. Both drugs contributed to reduction in neurotransmitter biotransformation.

AVE 0991-angiotensin-(1-7) receptor agonist, inhibits atherogenesis in apoE-knockout mice.

Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. It was also proved that Ang II promotes atherogenesis. Angiotensin-(1-7) [Ang-(1-7)] opposites Ang II action. Therefore, we would like to find out whether Ang-(1-7) receptor agonist: AVE 0991, could ameliorate atherosclerosis progression in an experimental model of atherosclerosis: apolipoprotein E (apoE) - knockout mice. AVE 0991 inhibited atherogenesis, measured both by "en face" method (7.63+/-1.6% vs. 14.6+/-2.1%) and "cross-section" method (47 235+/-7 546 microm(2) vs. 91 416+/-8 357 microm(2)). This is the first report showing the effect of AVE 0991 on atherogenesis in gene-targeted mice.

The effect of nebivolol on atherogenesis in apoE-knockout mice.

Nebivolol is a novel beta1-blocker with a nitric oxide (NO)--potentiating, vasodilatory effect that is unique among beta-blockers. It was already shown that nebivolol ameliorates atherosclerosis in cholesterol-fed rabbits. We, therefore, wanted to investigate whether this is the case in the fine experimental model of atherosclerosis: apolipoprotein E (apoE)-knockout mice. Nebivolol attenuated atherogenesis, measured both by "en face" method (9.23+/-1.8% vs. 14.6+/-2.1%) and "cross-section" method (63125+/-8455 microm(2) vs. 91416+/-8357 m(2)). This is the first report showing the effect of nebivolol on atherogenesis in gene-targeted mice.

Effect of gabapentin on cognitive processes in rats not exposed and exposed to tobacco smoke during fetal life.

Cognitive deficits, including memory deficiencies, are currently deemed one of key symptoms of psychopathologic mental disorders or epilepsy. The impairment of neurocognitive processes could be due to the administered therapy, in particular combined therapy or therapy using antiepileptics of older type. Gabapentin (GBP) is one of new antiepileptics with normothymic properties. It is known that epileptic patients run a significant risk of developing depression and mood changes. Smoking may also have a negative effect on memory processes and efficacy of administered drugs. Note that smoking in pregnant women also leads to neurobehavioral changes in their children. The objective of our research was to evaluate the effect of GBP on memory functions and antidepressant effect in rats not exposed and exposed to tobacco smoke in fetal life. We were also intent on finding whether GBP has an anticonvulsant effect in contact and without contact with tobacco smoke, and whether it affects motor coordination in animals if administered in the dose of 25 mg/kg. Spatial memory of the animals was assessed in the Morris test and the antidepressant effect in the Porsolt test. The ED(50) value was determined in the Swinyard maximum electric shock test, and the effect on motor coordination was assessed in the chimney test. GBP administered in the dose of 25 mg/kg intraperitoneal (i.p.) significantly reduced the immobility time on days 1 and 7 of the test in animals exposed to tobacco smoke, and on days 7 and 14 of the test in rats not exposed to tobacco smoke. Upon single and multiple administration of GBP to animals not exposed to tobacco smoke, the spatial memory improved, whereas in animals exposed to tobacco smoke in fetal life tolerance for procognitive effect was observed on day 21 of the test. It has been found that in rats not exposed to tobacco smoke, ED(50) of GBP was 28.73 mg/kg, whereas in animals exposed to tobacco smoke in fetal life, ED(50) was 46.2 mg/kg. Upon 14 and 21 days of drug administration, motor coordination was impaired in both GBP receiving animal groups. In conclusion, GBP beside its anticonvulsant efficacy also improves memory processes and has antidepressant effect. We also proved that GBP may reverse cognitive deficits concerning working memory induced by prenatal exposure to tobacco smoke and may have antidepressant effect in rats exposed to tobacco smoke.