Commentary: Sulfur Dioxide Contributes to the Cardiac and Mitochondrial Dysfunction in Rats

Commen

PERM Hypothesis: the fundamental machinery able to elucidate the role of xenobiotics and hormesis in cell survival and homeostasis

In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response. The "PERM hypothesis" suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch

Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies

Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies

Urinary carboxylic acids (UCAs) in subjects with autism spectrum disorder and their association with bacterial overgrowth

Abstract In this study, the levels of concentration of carboxylic acids (benzoic acid, p-hydroxybenzoic acid, p-hydroxyphenylacetic acid, and hippuric acid) in the urine of autistic children were investigated and compared. The increased excretion of carboxylic acids is related to excessive bacterial activity in the gut, called bacterial overgrowth, which has been related to autism spectrum disorder (ASD) as an impairment in the gut-brain axis. The investigation was based on the analysis of urine samples obtained from 120 ASD children. To identify and quantify urinary carboxylic acids (UCAs), we applied gas chromatography coupled with mass spectrometry (GC-MS). Additionally, we checked the influence of probiotic supplementation, gender, body mass index (BMI) value and age of children on the level of different selected compounds. Most of the obtained results were found within reference ranges. In some cases, the levels of benzoic acid, p-hydroxybenzoic acid, and p-hydroxyphenylacetic acid were particularly elevated. Statistically significant differences were observed in supplementation with probiotics and the level of p-hydroxyphenylacetic acid (p=0.036). The obtained results may indicate disturbances in the intestinal flora in some autistic patients and suggest that supplements may have an influence on the levels of carboxylic acids in urine. Due to the small population of children taking the supplement, further study are needed

Arealregnskap for utmark. Arealstatistikk for Finnmark

Mål og metode: I denne rapporten for Finnmark presenteres materiale som er samla inn i forbindelse med etableringa av et arealregnskap for utmark med basis i en nasjonal utvalgsundersøkelse av arealdekket. Materialet omfatter 164 utvalgsflater lagt systematisk ut over fylket. Disse flatene utgjør en liten, men likevel statistisk forventningsrett utvalgsundersøkelse av arealdekket. Spesielt vil materialet gi opplysninger om utmarka som utfyller registerdata og data fra andre undersøkelser. For arealtyper med mindre arealdekning enn 5 % vil usikkerheten være stor. Metoden som blir benytta i ”Arealregnskap for utmark” er ei utvalgskartlegging, nær knytta tilden europeiske Lucas-metoden, men tilpassa norske forhold. Målet er å gi noenlunde presiseresultat samla for Norge og for større regioner. Metoden tar utgangspunkt i et nettverk av storruter på 18 x 18 kilometer som er lagt ut i kartprojeksjonen UTM-33/WGS84. I sentrum av hver storrute er det plassert ei feltflate på 1500 x 600 meter (0,9 km2). Denne flata blir vegetasjonskartlagt etter Skog og landskap sin instruks for vegetasjonskartlegging på oversiktsnivå. I tillegg blir det samla inn data om arealdekke og arealbruk i 10 punkt innafor flata. Naturforhold: Finnmark ligger lengst nord og aust i Norge, og er det klart største av våre fylker. Det har ei lang og djupt innskåret kystlinje med lange og breie fjordstrekninger som deler opp landmassen til store halvøyer. Mest variert er landskapet i nordvest, med store øyer og sund, trange fjorder, tinder og breer. Kyst- og fjordlandskapet i Aust-Finnmark har vidder og platåfjell som brått ender mot en bratt næringskyst og åpent hav. Finnmarksvidda utgjør det meste av indre Finnmark og dekker mer enn tredjeparten av fylkesarealet. Det utjamna landskapet veksler mellom skogvidder, snaue åsdrag, myrer og vatn. Berggrunnen har stor betydning for variasjonen i vegetasjonstyper. Finnmark har ei markert todeling av fylket med en sørlig halvdel med hovedsakelig harde grunnfjellsbergarter, og en nordlig halvdel dominert av skyvedekker med sandsteiner, skifre, konglomerater og flere. Grunnfjellet med gneiser og granitter gir et næringsfattig jordsmonn. Her dominerer nøysomme vegetasjonstyper, mest lav- og lyngdominert skog og hei samt næringssvake myrer. Skyvedekkene med kambriske avsetninger i nord er svært variable i hardhet og næringsinnhold. Glimmerskifer, leirskifer, fyllitt, samt dolomittmarmor og andre karbonatbergarter er særlig gunstige for jordsmonndanning og plantevekst. Godt innslag av engbjørkeskog, rik sumpskog og engvegetasjon i fjellet er typisk her. Morene er den mest utbredte lausmassetypen i fylket. Den opptrer sparsomt i ytre deler, mens frekvens og mektighet auker sterkt mot indre deler. Størstedelen av furumoene i Finnmark ligger på tørre breelvavsetninger. Elveavsetninger er rik på finmateriale og danner oftest et næringsrikt jordsmonn. De er mest utbredt langs nedre deler av de største elvene. Hav- og fjordavsetninger forekommer i fjord- og kyststrøk og i nedre deler av dalføra. Forvitringsjord er mest utbredt der det er lause sedimentbergarter. Finnmark fylke med si vide utstrekning og vekslinger i topografi og høgdelag gir stor variasjon i temperatur og nedbør. Den nordlige beliggenheten setter også sitt preg på været. Klimaet følger i grove trekk det vanlige mønsteret fra kyst mot innland. På målestasjonene varierer årsmiddel for temperatur mellom ÷3,1 og +3,6 °C. Nedbøren varierer mellom 345 og 914 mm i årsnedbør. Finnmark er det nedbørfattigste fylket i Norge. Arealdekket i Finnmark: Av de 54 typene i kartleggingssystemet er 40 representert i fylket. I tillegg kommer ferskvatn der data er henta fra Statens kartverk sin database N50. Bare 7 typer dekker mer enn 5 % av arealet. 2e rishei er klart størst av disse med 21,2 %. Videre følger 2c lavhei og 4a lav- og lyngrik bjørkeskog, begge med 13,6 %, 12b ur og blokkmark 8,8 %, 9c grasmyr 6,5 % og ferskvatn 5,9 %. 10 typer har fra 1 til 5 % av arealet. Skoggrensa representerer et markert skille i voksevilkår og landskapsbilde, og utvalget av typer vil være forskjellig over og under denne grensa. Det er vanskelig å sette eksakt skoggrense i Finnmark da overgangene mellom skog og snaumark ofte er diffuse, og fordi det ofte er andre faktorer enn temperaturklimaet som setter grenser for skogutbredelsen. Utførte beregninger viser at 45 % av Finnmark ligger under skoggrensa og 55 % over. I Finnmark er 25 % av arealet dekt av skog. Under skoggrensa utgjør skogen 56 %. På 90 % av skogarealet er bjørk dominerende treslag, 9 % er furu og 1 % andre treslag der setervier, gråor og osp er de vanligste. 6 vegetasjons- eller arealtyper dekker mer enn 5 % av arealet under skoggrensa. Høgest dekning har 4a lav- og lyngrik bjørkeskog med 30,4 % av arealet. Videre følger 4b blåbærbjørkeskog 13,9 %, 2e rishei 10,5 %, 9c grasmyr 9,0 %, 9a rismyr 8,8 % og ferskvatn 8,3 %. 7 typer dekker mellom 1 og 5 % av arealet. I alt er 33 av 54 typer til stede her. Ferskvatn kommer i tillegg. Arealet over skoggrensa utgjør 55 % av arealet i Finnmark. Her kan vegetasjonen deles i lågalpin sone, mellomalpin sone og høgalpin sone. Snaufjellsarealet i Finnmark tilhører i hovedsak lågalpin sone. En liten del ligger i mellomalpin, mens høgalpin bare har en ubetydelig andel. 4 vegetasjons- eller arealtyper dekker 5 % eller mer av arealet over skoggrensa. 2e rishei med 29,7 % og 2c lavhei 22,7 %, har sterk dominans. 12b ur og blokkmark dekker 15,6 % av arealet og 1c frostmark, letype 5,4 %. 9 typer har mellom 1 og 5 % dekning. Til sammen er 30 vegetasjons- og arealtyper kartlagt over skoggrensa. Ferskvatn kommer i tillegg

Arsenic toxicity: Molecular targets and therapeutic agents

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered

Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation

Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment

Analytical and in silico study of the inclusion complexes between tropane alkaloids atropine and scopolamine with cyclodextrins

AbstractDatura stramonium L. (Solanaceae) possesses a rich tropane alkaloids (TAs) spectrum. The plant contains, in particular, the allelopathic compounds scopolamine and atropine, which are poorly soluble in water, thus limiting their use in agrochemical formulations as biocidal and deterrent agents against herbivore insects. The efficacy of the hydrophobic TAs extracts could be increased with the improvement of their dissolution/leaching properties. This is important for improving screening and test performance and for elucidating the activity of environmentally friendly agricultural approaches, with new perspectives for the production and use of those biodegradable insecticidal products. The present study explores the aspects of atropine and scopolamine complexation with cyclodextrin (CDs) through FT-IR and UV–Vis spectroscopies. In addition, the structures of the inclusion complex of atropine, scopolamine and β-CD have been investigated by molecular modeling techniques. The results obtained indicate that β-CDs are a promising carriers for improving the properties of TAs, therefore increasing their application potential in agrochemical formulations. Graphic abstrac

Immune dysfunction and neuroinflammation in autism spectrum disorder

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder with a complex pathogenesis. Many studies over the last four decades have recognized altered immune responses among individuals diagnosed with ASD. The purpose of this critical and comprehensive review is to examine the hypothesis that immune dysfunction is frequently present in those with ASD. It was found that often individuals diagnosed with ASD have alterations in immune cells such as T cells, B cells, monocytes, natural killer cells, and dendritic cells. Also, many individuals diagnosed with ASD have alterations in immunoglobulins and increased autoantibodies. Finally, a significant portion of individuals diagnosed with ASD have elevated peripheral cytokines and chemokines and associated neuroinflammation. In conclusion, immune dysregulation and inflammation are important components in the diagnosis and treatment of ASD

TiO2-Ag-NP adhesive photocatalytic films able to disinfect living indoor spaces with a straightforward approach

TiO2-Ag doped nanoparticulate (TiO2-Ag-NP) adhesive photocatalytic films were used to assess the ability in dropping down the burden of indoor microbial particles. The application of an easy-to use photocatalytic adhesive film to cleanse indoor living spaces from microbial pollution, represents a novelty in the field of photocatalytic devices. Reduction was attained by photocatalysis in selected spaces, usually with overcrowding (≥ 3 individuals) in the common working daily hours, and upon indoor microclimate monitoring. TiO2-Ag doped nanoparticulate (TiO2-Ag-NP) adhesive photocatalytic films were applied within five types of living spaces, including schools and job places. The microbial pollution was assessed at time 0 (far from routine clean, ≥ 9 h) and throughout 2-4 weeks following the photocatalyst application by relative light unit (RLU) luminometry and microbial indirect assessment (colony forming units per cubic meter, CFU/m3). TiO2-Ag-NP photocatalyst reduced RLU and CFU/m3 by rates higher than 70% leading to RLU ≤ 20 and microbial presence ≤ 35 CFU/m3. The described TiO2-Ag-NP is able to reduce microbial pollution to the lowest RLU threshold (≤ 20) within 60 min in open daylight in a standardized test room of 100 m2. The correlation between RLU and CFU/m3 was positive (r = 0.5545, p < 0.05), assessing that the microbial reduction of indoor areas by the TiO2-Ag-NP adhesive film was real. Titania photocatalysts represent promising tools to ensure air cleaning and sanitization in living indoor microclimates with a low cost, feasible and straightforward approach. This approach represents an easy to handle, cost effective, feasible and efficacious approach to reduce microbial pollution in indoor spaces, by simply attaching a TiO2-Ag-NP adhesive film on the wall