scholarly journals Study of Fecal and Urinary Metabolite Perturbations Induced by Chronic Ethanol Treatment in Mice by UHPLC-MS/MS Targeted Profiling

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 232 ◽  
Author(s):  
Olga Deda ◽  
Christina Virgiliou ◽  
Amvrosios Orfanidis ◽  
Helen G. Gika

Alcoholic liver disease (ALD) as a consequence of ethanol chronic consumption could lead to hepatic cirrhosis that is linked to high morbidity and mortality. Disease diagnosis is still very challenging and usually clear findings are obtained in the later stage of ALD. The profound effect of ethanol on metabolism can be depicted using metabolomics; thus, the discovery of novel biomarkers could shed light on the initiation and the progression of the ALD, serving diagnostic purposes. In the present study, Hydrophilic Interaction Liquid Chromatography tandem Mass Spectrometry HILIC-MS/MS based metabolomics analyisis of urine and fecal samples of C57BL/6 mice of both sexes at two sampling time points was performed, monitoring the effect of eight-week ethanol consumption. The altered hepatic metabolism caused by ethanol consumption induces extensive biochemical perturbations and changes in gut microbiota population on a great scale. Fecal samples were proven to be a suitable specimen for studying ALD since it was more vulnerable to the metabolic changes in comparison to urine samples. The metabolome of male mice was affected on a greater scale than the female metabolome due to ethanol exposure. Precursor small molecules of essential pathways of energy production responded to ethanol exposure. A meaningful correlation between the two studied specimens demonstrated the impact of ethanol in endogenous and symbiome metabolism.

2020 ◽  
Vol 10 (9) ◽  
pp. 658
Author(s):  
Richa S. Rathod ◽  
Carolyn Ferguson ◽  
Amit Seth ◽  
Annalisa M. Baratta ◽  
Sonja L. Plasil ◽  
...  

We and others previously reported that paternal preconception chronic ethanol exposure leads to molecular, physiological, and behavioral changes in offspring including reduced ethanol consumption and preference relative to controls. The goal of the present study was to further explore the impact of paternal ethanol exposure on a wide variety of basal and drug-induced behavioral responses in first generation offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5–6 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. E-sired male offspring showed stress hyporesponsivity in a stress-induced hyperthermia assay and E-sired female offspring had reduced binge-like ethanol consumption in a drinking in the dark assay compared to C-sired offspring. E-sired offspring also showed altered sensitivity to a sedative/hypnotic dose of the GABAergic drug midazolam, but not ketamine or ethanol, in a loss of the righting response assay. E-sired offspring did not differ from controls in marble burying, novel object location, novel object recognition, social interaction, bottle-brush, novelty suppressed feeding, prepulse inhibition, every-other-day ethanol drinking, or home cage activity assays. This study adds to a growing body of literature suggesting that like in utero alcohol exposure, paternal preconception alcohol exposure can also have effects that persist and impact behavior of offspring.


Author(s):  
Sonia -Mirén Martínez-González ◽  
Maria Concepción Martínez Rodríguez

Aunque las últimas técnicas de diagnóstico de la biotecnología médica son aplicadas en México, existe aún un porcentaje importante de personas que no tienen acceso a servicios de salud, resultado de la desigualdad económica en el país. Este artículo tiene como objetivo presentar el impacto en México de diversas enfermedades (COVID-19, enfermedad diarreica aguda, cáncer cervicouterino, cáncer de mama, leishmaniasis, lesiones renales agudas y neurocisticercosis), las estrategias implementadas en su diagnóstico y control, así como las perspectivas de pruebas de diagnóstico novedosas. El artículo se realizó a través de una revisión de documentos en línea del Gobierno mexicano y de artículos científicos que estudian la implementación y las características de las herramientas biotecnológicas para el diagnóstico de enfermedades. En el caso de la COVID-19, la disponibilidad de procedimientos certeros y rápidos para su diagnóstico ha demostrado ser de vital importancia en el control de la enfermedad, así como en el entendimiento de la infección y los procesos de inmunidad. En el caso de la enfermedad diarreica aguda derivada de la infección por rotavirus, la elevada morbilidad y mortalidad de enfermedades no puede ser completamente controlada hasta que mejore la calidad de vida de la población. Las herramientas de la biotecnología para el diagnóstico, aplicadas por medio de programas públicos dirigidos a la población vulnerable, proporcionan una forma de cerrar la brecha de salud entre zonas desarrolladas y en vías de desarrollo. Aun así, se debe considerar que la cantidad de recursos que se utilizan sigue siendo elevada.   Abstract Although the diagnostic techniques of medical biotechnology are being applied in Mexico, there is still a significant percentage of people who do not have access to health services, a result of the country's economic inequality. This article aims to present the impact in Mexico of several diseases (COVID-19, acute diarrheal disease, cervical cancer, breast cancer, leishmaniasis, acute kidney injury and neurocysticercosis), the strategies implemented in their diagnosis and control, as well as perspectives of novel diagnostic tests. The article was conducted through a review of online documents from the Mexican government and scientific articles that study the implementation and characteristics of biotechnological tools for disease diagnosis. In the case of COVID-19, the availability of accurate and rapid procedures for its diagnosis has proven to be of vital importance in the control of this disease, as well as in the understanding of infection and immunity processes. In the case of acute diarrheal disease resulting from rotavirus infection, the high morbidity and mortality of diseases cannot be completely controlled until the quality of life of the population is improved. The tools of biotechnology in diagnostics applied through public programs to vulnerable populations provide a way to close the health gap between developed and developing areas. Even so, it must be considered that the amount of resources they use is still high.


2019 ◽  
Vol 19 (6) ◽  
pp. 387-394 ◽  
Author(s):  
Li Xu ◽  
Long-Fei Wu ◽  
Fei-Yan Deng

Exosomes are 30-120nm long endocytic membrane-derived vesicles, which are secreted by various types of cells and stably present in body fluids, such as plasma, urine, saliva and breast milk. Exosomes participate in intercellular communication. Recently accumulative studies have suggested that exosomes may serve as novel biomarkers for disease diagnosis and prognosis. Herein, we reviewed the biological features of exosomes, technologies for exosome isolation and identification, as well as progress in exosomal biomarker identification, highlighting the relevance of exosome to human diseases and significance and great potential in translational medicine.


Author(s):  
Dianne Toe ◽  
Louise Paatsch ◽  
Amy Szarkowski

Deaf and hard-of-hearing (DHH) children who use spoken language face unique challenges when communicating with others who have typical hearing, particularly their peers. In such contexts, the social use of language has been recognized as an area of vulnerability among individuals in this population and has become a focus for research and intervention. The development of pragmatic skills intersects with many aspects of child development, including emotional intelligence and executive function, as well as social and emotional development. While all these areas are important, they are beyond the scope of this chapter, which highlights the impact of pragmatics on the specific area of cognition. Cognitive pragmatics is broadly defined as the study of the mental processes involved in the understanding of meaning in the context of a cooperative interaction. This chapter explores how DHH children and young people construe meaning in the context of conversations and expository interactions with their peers. The chapter aims to examine the role played by the cognitive processes of making inferences and comprehending implicature, within the overall display of pragmatic skills. Further, the authors use this lens in the analysis of interactions between DHH children and their peers in order to shed light on the development of pragmatic skills in children who are DHH.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kerrie Ní Dhufaigh ◽  
Eugene Dillon ◽  
Natasha Botwright ◽  
Anita Talbot ◽  
Ian O’Connor ◽  
...  

AbstractThe causative agent of amoebic gill disease, Neoparamoeba perurans is reported to lose virulence during prolonged in vitro maintenance. In this study, the impact of prolonged culture on N. perurans virulence and its proteome was investigated. Two isolates, attenuated and virulent, had their virulence assessed in an experimental trial using Atlantic salmon smolts and their bacterial community composition was evaluated by 16S rRNA Illumina MiSeq sequencing. Soluble proteins were isolated from three isolates: a newly acquired, virulent and attenuated N. perurans culture. Proteins were analysed using two-dimensional electrophoresis coupled with liquid chromatography tandem mass spectrometry (LC–MS/MS). The challenge trial using naïve smolts confirmed a loss in virulence in the attenuated N. perurans culture. A greater diversity of bacterial communities was found in the microbiome of the virulent isolate in contrast to a reduction in microbial community richness in the attenuated microbiome. A collated proteome database of N. perurans, Amoebozoa and four bacterial genera resulted in 24 proteins differentially expressed between the three cultures. The present LC–MS/MS results indicate protein synthesis, oxidative stress and immunomodulation are upregulated in a newly acquired N. perurans culture and future studies may exploit these protein identifications for therapeutic purposes in infected farmed fish.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Emma T Helm ◽  
Susanne J Lin ◽  
Nicholas Gabler ◽  
Eric R Burrough

Abstract Swine dysentery (SD) induced by Brachyspira hyodysentariae (Bhyo) causes colitis and mucohemorrhagic diarrhea in grow-finish pigs, however little is known about the physiological changes that occur to the gastrointestinal tract during Bhyo infection. Thus, the objective of this study was to evaluate the impact of a Bhyo challenge on intestinal function and integrity of pigs fed two divergent diets. A total of 36 Bhyo negative gilts (24.3 ± 3.6 kg BW) were selected and assigned to one of three treatment groups (n=12 pigs/trt): 1) Bhyo negative, 20% DDGS diet (CON), 2) Bhyo challenged, 20% DDGS diet (DDGS), and 3) Bhyo challenged, 10% DDGS, 5% beet pulp and 5% resistant potato starch diet (RS). Pigs were fed diets 21 days prior to challenge and on days post inoculation (dpi) 0 and 1, pigs were inoculated with Bhyo or sham. Fecal samples were collected for ATTD and pigs were euthanized for colon collection within 72 hours of initial observation of clinical SD, or at the end of the study (dpi 10-16). Tissues were assessed for ex vivo measures of intestinal integrity and mitochondrial function. The challenge resulted in high morbidity, with 88% of DDGS and RS pigs developing clinical SD. Colon transepithelial resistance was increased in DDGS pigs compared with CON and RS pigs (P=0.005), and colon macromolecule permeability was reduced in both DDGS and RS pigs compared with CON pigs (P=0.006), likely due to mucoid discharge. Colonic mitochondrial oxygen consumption was not impacted by treatment (P >0.10). Further, ATTD of DM, OM, N, and GE were reduced in DDGS pigs compared with CON pigs (P< 0.001), whilst nutrient digestibility was not reduced in RS pigs. Taken together, these data show Bhyo does not appear to reduce ex vivo colonic integrity. Further, the RS diet may reduce severity of a Bhyo challenge.


2020 ◽  
Vol 10 (1) ◽  
pp. 119
Author(s):  
Giorgia Grassi ◽  
Elisa Polledri ◽  
Silvia Fustinoni ◽  
Iacopo Chiodini ◽  
Ferruccio Ceriotti ◽  
...  

The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography in tandem with mass spectrometry (LC/MS-MS), in the diagnosis of PCOS. We evaluated 131 patients referred for suspected PCOS. Fourteen patients in total were excluded, some because of other diagnosis (n = 7) or incomplete diagnostic workup (n = 7). We measured T and A both by IA and LC-MS/MS in the 117 subjects included. We calculated free T (fT) by the Vermeulen formula and recorded clinical and metabolic data. 73 healthy females served as controls to derive immunoassays (IA) and LC-MS/MS reference intervals for T, fT and A. PCOS was confirmed in 90 subjects by IA and in 93 (+3.3%) by LC-MS/MS. The prevalence of biochemical hyperandrogenism in PCOS by LC-MS/MS increased from 81.7% to 89.2% if A was also considered. The most frequently elevated androgens were fT (73.1%) and A (64.5%) and they had similar levels of accuracy in differentiating PCOS and controls (0.34 ng/dL, Sn 91% Sp 89%; 1.16 ng/mL, Sn 91% Sp 88%, respectively). Free testosterone correlated with body mass index (BMI), homeostatic model assessment (HOMA)-index, glycated hemoglobin (HbA1c), and sex-binding globulin (SHBG). The results confirm that LC-MS/MS is slightly more sensitive than IA in the diagnosis of PCOS with LC-MS/MS detecting higher levels of fT and A. Moreover, assessment of fT and A by LC-MS/MS had a similar level of accuracy in discriminating between PCOs and control subjects. Lastly, fT by LC-MS/MS correlates with adverse metabolic parameters.


2010 ◽  
Vol 3 (6) ◽  
pp. 414-420 ◽  
Author(s):  
Subir Kumar Das ◽  
Sukhes Mukherjee

Background: Alcohol abuse is a systemic disorder. The deleterious health effects of alcohol consumption may result in irreversible organ damage. By contrast, there currently is little evidence for the toxicity of chronic alcohol use on lung tissue. Hence, in this study we investigated long-term effects of ethanol in the lung.Results: Though body weight of rats increased significantly with duration of exposure compared to its initial weight, there was no significant change in relative weight (g/100 g body weight) of lung due to ethanol exposure. The levels of thiobarbituric acid reactive substances (TBARS), nitrite, protein carbonyl, oxidized glutathione (GSS G), redox ratio (GSS G/ GSH ) and GST activity elevated; while reduced glutathione (GSH ) level and activities of glutathione reductase (GR), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and Na+K+ATPase reduced significantly with duration of ethanol exposure in the lung homogenate compared to the control group. Total matrix metalloproteinase activity elevated in the lung homogenate with time of ethanol consumption. Histopathologic examination also demonstrated that severity of lung injury enhanced with duration of ethanol exposure.Methods: 16–18 week-old male albino Wistar strain rats weighing 200–220 g were fed with ethanol (1.6 g/kg body weight/day) up to 36 weeks. At the end of the experimental period, blood samples were collected from reteroorbital plexus to determine blood alcohol concentration and the animals were sacrificed. Various oxidative stress-related biochemical parameters, total matrix metalloproteinase activity and histopathologic examinations of the lung tissues were performed.Conclusions: Results of this study indicate that long-term ethanol administration aggravates systemic and local oxidative stress, which may be associated with lung tissue injury.


2015 ◽  
Vol 42 (2) ◽  
pp. 170-185 ◽  
Author(s):  
David Zimmer

Purpose – The US Medicare Modernization Act of 2003 introduced optional prescription drug coverage, beginning in 2006, widely known as Medicare Part D. This paper uses up-to-date nationally representative survey data to investigate the impact of Part D not only on drug spending and consumption, but also on the composition of drug consumption. The paper aims to discuss these issues. Design/methodology/approach – Specifically, the paper investigates whether Part D impacted the number of therapeutic classes for which drugs were prescribed, and also whether Part D lead to increased usage of drugs for specific medical conditions that typically receive drug-intensive therapies. Findings – In addition to confirming findings from previous studies, this paper shows that Part D increased the number of therapeutic classes to which seniors receive drugs by approximately four classes. Part D also lead to increased usage of drugs used to treat upper respiratory disease, hypertension, and diabetes. Originality/value – While mostly concurring with previous studies on the spending impacts of Part D, this paper is the first to shed light on other impacts of Part D, specifically with respect to its impact on therapeutic classes for which drugs are prescribed.


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