Development of QSAR machine learning-based models to forecast the effect of substances on malignant melanoma cells.

SK-MEL-5 is a human melanoma cell line that has been used in various studies to explore new therapies against melanoma in different experiments. Based on this study we report on the development of quantitative structure-activity relationship (QSAR) models able to predict the cytotoxic effect of diverse chemical compounds on this cancer cell line. The dataset of cytotoxic and inactive compounds were downloaded from the PubChem database.

New Metabolic Influencer on Oxytocin Release: The Ghrelin.

Background: The hypothalamic⁻pituitary axis by secreting neuropeptides plays a key role in metabolic homeostasis. In light of the metabolic regulation, oxytocin is a potential neuropeptide for therapies against obesity and related disorders. The aim of our study is to measure ghrelin-induced oxytocin secretion in rats and to detect the changes after administration of ghrelin antagonist.

Temporal structure in spiking patterns of ganglion cells defines perceptual thresholds in rodents with subretinal prosthesis.

Subretinal prostheses are designed to restore sight in patients blinded by retinal degeneration using electrical stimulation of the inner retinal neurons. To relate retinal output to perception, we studied behavioral thresholds in blind rats with photovoltaic subretinal prostheses stimulated by full-field pulsed illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to changes in brightness, with an average contrast threshold of 12%, which could not be explained by changes in the average RGC spiking rate.

Ghrelin-Induced Enhancement of Vasopressin and Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures.

The effects of ghrelin on vasopressin and oxytocin secretion were studied in 13-14-day cell cultures of isolated rat neurohypophyseal tissue. The vasopressin and oxytocin contents of the supernatant were determined by radioimmunoassay after a 1- or 2-h incubation. Significantly increased levels of vasopressin and oxytocin production were detected in the cell culture media following ghrelin administration, depending on the ghrelin doses.

Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause.

Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated.

Does chronic stress enhance the risk of diseases?

Objective: In the everyday life, stress is deemed as something unfavorable that may enhance the risk for the development or worsen a disease. However, in its nature, stress is adaptive reaction of the body. Its main characteristic is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis.

Reliability of anthropometric parameters in the prediction of the visceral fat area among adult women.

Visceral fat accumulation is a risk factor for cardiometabolic diseases. Magnetic resonance imaging (MRI) and computed tomography (CT) provided the most accurate techniques of abdominal fat assessment, but these methods are very expensive. The aim of this study was to examine and compare the predictive ability of simple anthropometric parameters for visceral fat area (VFA) among adult women in different age and obesity status groups.

Thrombin split products (prothrombin fragment 1 + 2) in urine in patients with suspected deep vein thrombosis admitted for radiological verification.

Introduction: The appearance of prothrombin fragment 1 + 2 (F1 + 2) in urine has been associated with postoperative hypercoagulability and thromboembolism. We wanted to assess if F1 + 2 was released in urine (uF1 + 2) in patients with procoagulant disorders, and if higher levels were found in patients with radiological verified deep vein thrombosis (DVT).

Materials And Methods: Consecutive patients were interviewed on comorbidities and medications.

The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats.

The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250 g). Different doses (10, 30, and 90 μg/10 μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30 μg/10 μl) were administered intracerebroventricularly (i.c.

Effects of orexin-monoaminergic interactions on oxytocin secretion in rat neurohypophyseal cell cultures.

The effects of orexin-monoaminergic compound interactions on oxytocin release were studied in 14-day rat neurohypophyseal cell cultures prepared by an enzymatic dissociation technique. The oxytocin contents of the supernatants were determined by radioimmunoassay. Following the administration of orexin-A or orexin-B in increasing doses, significant changes were not observed in the oxytocin content of the supernatant media.

Behavioral and endocrine effects of chronic exposure to low doses of chlorobenzenes in Wistar rats.

Chlorobenzenes have often been applied to study persistent organic pollutants with endocrine disruptor effects (POP/EDCs), but with the focus mainly on physiological aspects. Few data exist on the effects of chlorobenzenes and most POP/EDCs on anxiety or other arginine-vasopressin (AVP)- and oxytocin (OXT)-mediated behavior, albeit exposure to POP/EDCs or their ambient mixtures, even in low doses, may pose health risks for subjects living in contaminated areas and/or consuming polluted food. Our primary aim was therefore to demonstrate behavioral effects of longterm exposure to a discrete dose of a chlorobenzene mixture, and to draw attention to the results of subtoxic oral exposure on anxiety-related elements and the possible underlying endocrine processes.

The effects of orexins on monoaminerg-induced changes in vasopressin level in rat neurohypophyseal cell cultures.

The effects of orexin-monoaminergic compound interactions on vasopressin release were studied in 14-day neurohypophyseal cell cultures from adult rats, prepared by an enzymatic dissociation technique. The vasopressin contents of the supernatants were determined by radioimmunoassay. Following administration of either orexin-A or orexin-B in increasing doses, significant changes were not observed in the vasopressin levels of the supernatant media.

Further analysis of behavioral and endocrine consequences of chronic exposure of male Wistar rats to subtoxic doses of endocrine disruptor chlorobenzenes.

Many chemicals utilized by humans are present as environmental pollutants and may influence homeostasis from neurological, immunological, endocrinological and/or behavioral aspects. Such agents, acting alone or in ambient mixtures, may be biologically active even at extremely low doses, and it may be postulated that stable, bioaccumulative, reactive endocrine disruptors may affect central and/or peripheral secretion of arginine-vasopressin (AVP) and oxytocin (OXT) and thereby related physiological and behavioral functions, potentially leading to disorders in exposed subjects. The primary aim of this study was to demonstrate effects of chronic exposure to a low dose of an orally administered chlorobenzene mixture on anxiety-related and aggressive behavior mediated largely by AVP and OXT.

Inhibitory effect of galanin on adrenaline- and noradrenaline-induced increased oxytocin secretion in rat neurohypophyseal cell cultures.

The effects of the interactions between the 29 amino acid-containing peptide galanin and adrenaline or noradrenaline on the secretion of oxytocin were studied in 13- to 14-day cultures of isolated rat neurohypophyseal tissue. The alpha-receptor antagonist corynanthine blocked the adrenaline-induced increase of oxytocin secretion. When the beta-receptor antagonist propranolol was added before the noradrenaline treatment, the antagonist prevented the noradrenaline-induced enhancement of oxytocin release.

Protective effect of ischaemic preconditioning on ischaemia/reperfusion-induced microvascular obstruction determined by on-line measurements of coronary pressure and blood flow in pigs.

We investigated the protective effect of ischaemic preconditioning (IP) on the maintenance of coronary patency using on-line measurements of coronary pressures and blood flow in a closed-chest reperfused acute myocardial infarction (MI) model in pigs. Catheter-based 90-min occlusion followed by 60-min reperfusion of the left anterior descending coronary artery (LAD) was performed in anesthetised pigs (MI group). IP was applied (IP group) through two cycles of 5-min occlusion and 5-min reperfusion of the LAD before MI induction.

Effects of galanin-monoaminergic interactions on vasopressin secretion in rat neurohypophyseal cell cultures.

The effects of dopamine (DA), serotonin (5-HT), histamine (HA), adrenaline (ADR), noradrenaline (NADR) and K(+) administration on vasopressin (VP) secretion were studied in 13-14-day cultures of rat neurohypophyseal (NH) cells, and it was examined whether galanin (GAL) can modify the VP release enhancement induced by these monoaminergic compounds. An enzymatic dissociation technique was used to make the rat NH cell cultures. The VP contents of the supernatants of 14-day cultures were determined by radioimmunoassay.

Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes.

Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (Abeta) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR.

Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260.

The numerous situations which can result in cerebral hypoxic damage occur in newborn infants and in the elderly. In research aimed at more effective therapeutic intervention in ischaemic disorders of the brain, the animal model used and the principles of the causal therapy should be better outlined. The effects of the non-peptide AVPR (V2) antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats.

Significance of the adrenergic system in the regulation of vasopressin secretion in rat neurohypophyseal tissue cultures.

Unlabelled: The effects of adrenaline (A) and noradrenaline (NA) on vasopressin (VP) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP contents of the supernatant media were determined by radioimmunoassay after a 1 or 2-h incubation. Significantly increased VP levels were detected in the tissue culture media following the administration of A (an alpha+beta(2)-receptor agonist), depending on the dose of A.

Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia.

The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration.

The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis.

The mechanism of action of 5-aminosalicylic acid (5-ASA), the active therapeutic moiety of a number of clinically used anti-colitic agents, is unclear. The present study investigates whether the beneficial effects in vivo could involve induction of the heat shock protein, heme oxygenase-1 (HO-1), known to provide endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation. The effects of 5-ASA on the colonic expression and activity of HO-1 along with its effect on the inflammatory damage have been evaluated in the colitis provoked by instillation of trinitrobenzene sulphonic acid (TNBS) over 48 h in the rat.

Modulation by heme and zinc protoporphyrin of colonic heme oxygenase-1 and experimental inflammatory bowel disease in the rat.

Reactive oxygen species, suggested to be involved in inflammatory bowel disease, may be modulated by endogenous anti-oxidant products of heme oxygenase-1 (HO-1). In the present work, HO-1 expression in trinitrobenzene sulphonic acid (TNBS)-induced colitis in the rat and the effects of HO-1 modulation, particularly by the HO-1 inducer, heme, were further evaluated. Colitis was induced by intracolonic challenge with TNBS and assessed macroscopically and by myeloperoxidase (MPO) assay.

Biological half-life and organ distribution of [3H]8-arginine vasopressin following administration of vasopressin receptor antagonist OPC-31260.

The effects of the antidiuretic (V(2)) non-peptide receptor antagonist OPC-31260 on the plasma vasopressin level and the biological half-life and organ distribution of radiochemically pure, biologically active [(3)H]8-arginine vasopressin [spec. act.: 15.