Effect of Fasciola hepatica proteins on the functioning of rat hepatocytes

Fasciolosis is a hepatic parasitic infection that affects many mammal species and creates a great economic and veterinary problem. Molecular mechanisms of parasite–hepatocyte interactions have not been precisely characterized yet. Therefore, the aim of the study was to investigate alterations in the metabolic activity of rat liver cells exposed to Fasciola hepatica somatic proteins. Hepatocytes were incubated with 0–1 mg/ml of fluke's somatic proteins for various periods of time. Afterward, changes in hepatocytes metabolic activity were determined with MTT and enzyme leakage tests. Hepatocytes' capacity to synthesize albumin was also investigated. It was observed that protein concentration, as well as longevity of their action, influenced metabolic activity of rat liver cells. Diminution of hepatocytes survival rate, an increase in enzyme leakage and altered synthetic capacity after treatment with parasite's proteins were reported. It is concluded that somatic proteins of F. hepatica may play an important role in liver cell damaging

Paradoxical antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis

Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking—but not forced alcohol exposure—reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-016-1658-6) contains supplementary material, which is available to authorized users

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias

Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures

The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

Abstract Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias

Excessive fit in decision trees

W pracy staramy się sprawdzić wpływ jaki ma dobór kryterium wyboru testu na nadmierne dopasowanie w drzewach decyzyjnych. Uważamy, że losowe kryterium doboru może okazać się nie gorsze od kryterium entropijnego. Nasze przypuszczenia potwierdzają wstępne badania wykonane dla trzech (niewielkich rozmiarów) zbiorach trenujących, co w naszej opinii zasługuje na dalsze eksperymenty.In this paper we try to check the influence of selection criteria for the test selection for excessive fit in decision trees. We believe that a random criteria selection may not be worse than the criteria of entropy. Our supposition is confirmed by preliminary tests performed for three training sets, which in our opinion deserves further experiments

Analiza założeń doboru składowych instalacji do wtórnej segregacji odpadów na terenie wybranej gminy

In recent years systemic changes in waste management have affected searching and implementation of solutions that increase waste recovery including those intended for recycle. The article presents a predicted amount of municipal waste intended for recovery based on their selected streams. For the needs of a conceptual solution the area was determined, which was operated by the mentioned installation. The paper uses the indicators of waste accumulation: mass, volume, bulk density and irregularity of their collection in 2011-2013 for determination of the sorting plant efficiency. Elements of the installation, which should enable optimization of the waste recovery process optimization, were selected. Moreover, frames of technological efficiency of the suggested solution were defined. The aim of the paper was an attempt to select parameters of a municipal waste sorting plant with location under conditions of Stary Sącz city.Zmiany systemowe w gospodarce odpadami w ostatnich latach wpływają na poszukiwanie i wdrażanie rozwiązań zwiększających odzysk odpadów, w tym przeznaczanych do recyklingu. W artykule zawarto przewidywaną do odzysku ilość odpadów komunalnych na podstawie wybranych ich strumieni. Dla potrzeb koncepcyjnego rozwiązania wyznaczono obszar, który byłby obsługiwany przez wspomnianą instalację. W pracy wykorzystano wskaźniki nagromadzenia odpadów: masowy, objętościowy i gęstość nasypową, a także rozpoznano nierównomierność ich nagromadzenia w latach 2011-2013 dla wyznaczenia wydajności sortowni. Dobrano części składowe instalacji, które powinny umożliwić optymalizację procesu odzysku odpadów. Określono również ramy efektywności technologicznej zaproponowanego rozwiązania. Celem pracy była próba doboru parametrów sortowni odpadów komunalnych wraz z lokalizacją w warunkach miasta Stary Sącz