NPY and NPY receptors in vascular remodeling

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors (Y1-Y6) and exerts a variety of cardiovascular effects. Originally known as a vasoconstrictor acting on Y1 receptors, NPY is also a potent angiogenic factor as well as a powerful stimulator of vascular smooth muscle proliferation and atherogenesis in vitro and in vivo. These two types of vascular remodeling are predominantly mediated by Y2/Y5 and Y1 receptors respectively, but evidence suggests that all receptors are activated in both conditions. A strategy to inhibit neointima formation and atherosclerotic lesions without impairing ischemic angiogenesis and collateral vessel formation has been a major challenge to overcome. Studies in rodents show that Y1 receptor antagonist inhibits angioplasty-induced atherosclerotic-like vascular remodeling, without affecting ischemic revascularization. Conversely, Y2 receptor activation appears to be sufficient to stimulate angiogenesis in various animal models. Thus, the use of selective receptor agonists to promote angiogenesis through the Y2 receptor while antagonizing the pro-atherosclerotic and pro-stenotic effects with Y1 receptor-selective antagonists may help to successfully treat vascular remodeling in cardiovascular diseases.     

Effect of repeated co-treatment with imipramine and metyrapone on the behavioral reactivity of the central serotonin, dopamine and alpha 1-adrenergic systems in rats

The aim of present study was to examine the effect of repeated co-treatment with imipramine and metyrapone on the development of adaptive changes in the function of central serotonin 5-HT1A and 5-HT2A, dopamine D2/3 and alpha 1-adrenergic receptors in rats. The obtained results showed that repeated co-treatment with imipramine (5 or 10 mg/kg) and metyrapone (50 mg/kg) (twice daily for 14 days) either induced more potent inhibition of the behavioral syndrome evoked by 5-HT1A and 5-HT2A receptor agonists (8-OH-DPAT and (+/-)DOI, respectively), or did no change the action of amphetamine and wuinpirole (a dopamine D2/3 agonist) or phenylephrine (an alpha 1-adrenergic agonist) compared to treatment with either drug alone. The results described in the present paper support the hypothesis that repeated co-treatment with imipramine and metyrapone may possess more effective antidepressant activity than the treatment with imipramine alone, and that, among other mechanisms, 5-HT1A- and 5-HT2A (but not dopamine D2/3- or alpha 1-adrenergic) receptors may also play some role in this effect.     

Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression

The paper describes the effect of amantadine addition to imipramine therapy in patients suffering from treatment-resistant unipolar depression who fulfilled DSM IV criteria for major (unipolar) depression. Fifty patients were enrolled in the study on the basis of their histories of illness and therapy. After a 2-week drug-free period, 25 subjects belonging to the first group were treated only with imipramine twice daily (100 mg/day) for 12 weeks, and 25 subjects belonging to the second group were treated with imipramine twice daily (100 mg/day) for 6 weeks and then amantadine was introduced (150 mg/day, twice daily) and administered jointly with imipramine for the successive 6 weeks. Hamilton Depression Rating Scale (HDRS) was used to assess the efficacy of antidepressant therapy. Imipramine did not change the HDRS score after 3, 6 or 12 weeks of treatment when compared with the washout (before treatment). The addition of amantadine to the classic antidepressant reduced HDRS scores after 6-week joint treatment. Moreover, the obtained pharmacokinetic data indicated that amantadine did not significantly influence the plasma concentration of imipramine and its metabolite desipramine in patients treated jointly with imipramine and amantadine, which suggests lack of a pharmacokinetic interaction. The obtained results indicate that joint therapy with an antidepressant and amantadine may be effective in treatment-resistant unipolar depression.     

Antidepressant-like effect of combined treatment with selective sigma receptor agonists and a 5-HT1A receptor agonist in the forced swimming test in rats

The interaction between the selective sigma (sigma) receptor agonists and 8-OH-DPAT, a serotonin (5-HT)(1A) receptor agonist, was examined in the forced swimming test in rats. The results indicate that joint administration of DTG (5 mg/kg) or SA4503 (3 mg/kg), the selective sigma(1)/sigma(2)- or sigma(1)-receptor agonists, respectively, and 8-OH-DPAT (0.1 or 0.3 mg/kg) induces an antidepressant-like effect. The doses of sigma agonists and 8-OH-DPAT used in the study were inactive per se in this model. The effect of DTG and 8-OH-DPAT co-administration was partly counteracted by WAY 100635 (0.1 mg/kg) as well as by BD 1047 (3 mg/kg), a 5-HT(1A) and sigma(1) receptor antagonists, respectively, suggesting the involvement of both receptor types in the anti-immobility effect in rats.     

Correlation between foveal structure and visual outcome following macular hole surgery: a spectral optical coherence tomography study

PURPOSE: The aim of this paper is to evaluate the retinal structure after macular hole surgery and to study the correlation of structural findings with final functional outcomes, using high-speed, high-resolution spectral optical coherence tomography (SOCT). METHODS: Sixty-eight eyes of 60 patients with full-thickness macular holes were included in the study. All patients underwent pars plana vitrectomy with trypan blue staining and internal limiting membrane (ILM) peeling. Patients were evaluated by SOCT, with 6 mum axial and 12-18 mum transverse resolution and three-dimensional images of the retina. RESULTS: There were four different types of macular hole closure: U-shape, V-shape, irregular and flat/open. The following retinal abnormalities were observed in postoperative scans: photoreceptor irregularities, lack of photoreceptors (photoreceptor defect), cysts in outer retinal layers, nerve fiber layer defects, lesion of all retinal layers, and RPE defects. It was possible to evaluate photoreceptor defects on a three-dimensional image. Retinal thickness in the fovea was also measured. CONCLUSIONS: Because of excellent resolution, SOCT is capable of visualization of retinal defects after macular hole surgery. Three-dimensional examination is adequate for evaluation of photoreceptor defects. Good postoperative visual acuity is correlated with U-shape closure, normal foveal thickness and absence of photoreceptor layer defects.     

Oscillations of cerebrovascular resistance throughout the menstrual cycle in healthy women.

OBJECTIVES: Increased concentration of endogenous estrogen during a typical menstrual cycle has been shown to correlate with augmentation of blood flow through the internal carotid arteries (ICAs), which may be related to changes in vascular resistance within the brain. In this study we investigated the effects of endogenous estrogen and progesterone on cerebrovascular impedance in young healthy women. METHODS: The blood flow in the ICA and the common (CCA) and external (ECA) carotid arteries was studied with duplex Doppler sonography. The resistance index (RI) was determined and correlated with plasma 17beta-estradiol concentration in 14 young healthy women throughout their menstrual cycle. RESULTS: The concentration of 17beta-estradiol increased in the follicular phase of the cycle and reached a peak on day 14, whereas concentration of progesterone remained low. Along with an increase in estrogen concentration, the ICA RI had decreased from its initial level on average by 9.2% on day 13 and by 6.7% on day 14 (P < 0.05). In contrast, the trend of the ECA RI was to increase during the peak of estrogen concentration. There were no significant changes in the CCA RI or in the systolic blood pressure, heart rate, hematocrit and hemoglobin concentration through the menstrual cycle. CONCLUSIONS: Estrogen-related augmentation of blood flow through the ICA is caused mainly by decreased cerebrovascular impedance, as shown by a decrease in the ICA RI. These changes in RI suggest that estrogen influences cerebral impedance mainly by altering the resistance of cerebral microvasculature.     

Y-STR variation among Slavs: evidence for the Slavic homeland in the middle Dnieper basin

A set of 18 Y-chromosomal microsatellite loci was analysed in 568 males from Poland, Slovakia and three regions of Belarus. The results were compared to data available for 2,937 Y chromosome samples from 20 other Slavic populations. Lack of relationship between linguistic, geographic and historical relations between Slavic populations and Y-short tandem repeat (STR) haplotype distribution was observed. Two genetically distant groups of Slavic populations were revealed: one encompassing all Western-Slavic, Eastern-Slavic, and two Southern-Slavic populations, and one encompassing all remaining Southern Slavs. An analysis of molecular variance (AMOVA) based on Y-chromosomal STRs showed that the variation observed between the two population groups was 4.3%, and was higher than the level of genetic variance among populations within the groups (1.2%). Homogeneity of northern Slavic paternal lineages in Europe was shown to stretch from the Alps to the upper Volga and involve ethnicities speaking completely different branches of Slavic languages. The central position of the population of Ukraine in the network of insignificant AMOVA comparisons, and the lack of traces of significant contribution of ancient tribes inhabiting present-day Poland to the gene pool of Eastern and Southern Slavs, support hypothesis placing the earliest known homeland of Slavs in the middle Dnieper basin.     

Acid-catalyzed synthesis of oxathiolone fused chalcones. Comparison of their activity toward various microorganisms and human cancer cells line

Substituted oxathiolone fused chalcones were prepared by condensation of 4-acetyl-5-methoxy-2-oxo-benz[1,3]oxathiole with benzaldehydes under acidic conditions. The compounds were tested for cytotoxic, antibacterial, antifungal and tuberculostatic activity. Three derivatives demonstrated weak activity against HeLa cells, two were slightly active against Micrococcus luteus and Staphylococcus aureus, and one was active against Mycobacterium tuberculosis H(37)Rv.     

Flanker task with equiprobable congruent and incongruent conditions does not elicit the conflict N2

In many published studies, various modifications of the flanker task have been used. Regardless of the flanker task version, the conflict N2 component has been consistently reported and interpreted as evidence for the resolution of conflict introduced by incongruent flankers. However, ERP studies that used the most basic flanker task (i.e., a version with equiprobable congruent and incongruent conditions in which only congruency between the target and flankers is manipulated) have not provided compelling evidence for the conflict N2 component. We report the results of a large‐sample ERP study employing a basic flanker task that allowed us to revisit the mechanism underlying the resolution of conflict introduced by incongruent flankers. In the behavioral data, we observed the classic effect of congruency. In the ERP data, we found three conflict‐sensitive components: (a) an early frontal component, presumably corresponding to P2, (b) P300 for congruent trials, followed by (c) P300 for incongruent trials. We did not find evidence for the conflict N2 component. Based on a review of literature, we propose that the conflict N2 component observed in a basic flanker task might be a frontal aspect of the P300 component. Given previous attempts to attribute the functional role of the ERP components, the absence of the conflict N2 in the basic flanker task suggests that response inhibition may not be crucial for the resolution of conflict induced by incongruent flankers. Instead, the P2 component appears to indicate that selective attention might play an important role in resolving the flanker conflict.