Skadelige effekter på nevroutvikling forårsaket av en humanrelevant blanding av persistente organiske miljøgifter (POPs) og perfluorooktansulfonsyre (PFOS)

Persistent organic pollutants (POPs) are ubiquitous in the environment. Humans are continuously exposed to chemical mixtures through food and the environment. Exposure to POPs have been associated with several adverse effects on human health including impaired brain development, cognition, and behaviour. The developing central nervous system appears to be more susceptible to toxic insults and several POPs are suspected to be developmental neurotoxicants. In the present thesis we used a POP mixture, containing 29 different compounds, based on being prominent in food, breast milk or blood from the Scandinavian human population. Perfluorooctane sulfonic acid (PFOS) alone, a potential neurodevelopmental toxicant, was also evaluated. We hypothesized that exposure to POPs during sensitive periods of early development could adversely affect key neurodevelopmental processes. To address this, we used the chicken embryo focussing on cerebellum and PC12 rat pheochromocytoma cells, as experimental models. Our results showed that exposure to POPs not only induced toxicity on their own but also aggravated glutamate-induced excitotoxicity in cultured cerebellar granule neurons (CGNs). Observations indicated a Ca2+-independent, but still N-methyl-D-aspartate receptor (NMDA-R) dependent mechanism in the absence of glutamate, and a Ca2+- and NMDA-R dependent mechanism in the presence of glutamate. Further, we found that CGN-sensitivity increased with the maturation in culture. POP exposures enhanced neurite length and branched networks of neurites in nerve growth factor (NGF)-induced PC12 cells, indicating the POPs interference with neuronal connectivity. However, in the absence of NGF, the effects of POPs on neurite outgrowth were marginal, suggesting that exposure cannot mimic the NGF-receptor signal on its own. POP mixture injected into the allantois distributed to the brain of developing chicken embryo in a concentration relevant for human exposure. However, the speed of distribution differed, with the protein binding per- and polyfluoroalkyl substances (PFASs) reaching the brain slower than the lipophilic polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). This reflects that distribution speed of the compounds depends on the chemical properties of different classes of compounds present in the mixture. POP exposure induced alterations at the levels of cerebellar morphology and affected gene and protein expression profiles that can interfere with fundamental aspects of neurodevelopmental processes. Our results showed alterations in molecular events linked to neuronal cell proliferation and migration, cellular stress responses including unfolded protein response, lipid metabolism, and myelination. Exposure to the POP mixture increased protein oxidation, whereas PFOS decreased oxidation. Our studies provide possible mechanistic explanations for associations between POP exposure and adverse neurodevelopmental and cognitive outcomes observed in epidemiological studies. Overall, we conclude that exposure to POPs could lead to morphological and molecular changes that interfere with fundamental aspects of neurodevelopment.Persistente organiske miljøgifter (POP) finnes over alt i miljøet. Mennesker blir kontinuerlig eksponert for blandinger av disse kjemikaliene fra ulike kilder. Eksponering for POP har vært assosiert med flere uønskede effekter på menneskers helse, blant annet effekter på hjernens utvikling og funksjon. Utviklingen av sentralnervesystemet synes å være særlig utsatt for skadelige effekter knyttet til eksponering med POPs. I denne oppgaven brukte vi en POP-blanding, som inneholder 29 forskjellige forbindelser. Disse er basert på forekomst i mat, morsmelk eller blod fra den skandinaviske befolkningen. Perfluorooktansulfonsyre (PFOS), som er vist å ha skadelige effekter på nevroutvikling, ble i tillegg undersøkt som enkeltstoff. Vår hypotese var at eksponering for POPs i tidlige utviklingssstadier kunne ha negative effekter på viktige trinn i nevroutviklingen. For å belyse denne problemstillingen eksperimentelt, brukte vi kyllingembryo og isolerte granulærceller fra kyllingenes lillehjerne (CGN). I tillegg brukte vi en feokromocytomcellelinje fra rotte (PC12). Resultatene viste at eksponering for POPs ikke bare induserte toksisitet alene, men også forverret glutamatindusert eksitotoksisitet i isolerte CGN-celler. Våre funn indikerte en Ca2+ -uavhengig, men fortsatt N-metyl-D-aspartat reseptor (NMDA-R) -avhengig mekanisme i fravær av glutamat, og en Ca2+- og NMDA-R-avhengig mekanisme i nærvær av glutamat. Videre fant vi at granulærcellenes følsomhet for eksponering i kultur økte med modningsgraden. Eksponering med POPs førte til økt neurittlengde og antall forgrenede nettverk av neuritter i PC12-celler som var tilsatt nervevekstfaktor (NGF). Dette indikerer at POPs kan forstyrre forbindelsen mellom nervecellene. I fravær av NGF, var imidlertid effekten av POPs på neurittutvekst marginal, noe som tyder på at POPs alene ikke kan etterligne NGF-reseptorsignalet. Blandingen av POPs ble injisert i kyllingegg for å undersøke om og hvordan de ulike stoffene i blandingen distribueres til hjernen hos kyllingembryo. Vi fant at POP-blanding injisert i allantois ble distribuert til hjernen i konsentrasjoner som er relevante for human eksponering. Distribusjonshastigheten varierte avhengig av stoffenes kjemiske egenskaper. Proteinbindende per- og polyfluoralkylstoffer (PFAS) nådde hjernen langsommere enn de lipofile polyklorerte bifenylene (PCB), organoklorpesticider (OCP) og bromerte flammehemmere (BFR). POP-eksponering av kyllingembryo induserte endringer i lillehjernens morfologi og påvirket gen- og proteinuttrykksprofiler knyttet til nevroutviklingsprosesser. Resultatene viste endringer knyttet til neuronal celleproliferasjon og migrasjon, cellulære stressresponser inkludert utfoldet proteinrespons, lipidmetabolisme og myelinisering. Eksponering for POP-blandingen økte proteinoksidasjonen, mens PFOS reduserte oksidasjonen. Våre studier peker på mulige mekanistiske forklaringer knyttet til sammenhenger mellom POP-eksponering og uønskede nevroutviklings- og kognitive utfall påvist i epidemiologiske studier. Samlet sett fant vi at eksponering med POPs er forbundet med morfologiske og molekylære endringer som kan interferere med nevroutvikling

Growth, Characterization, Vortex Pinning and Vortex Flow Properties of Single Crystals of Iron Chalcogenide Superconductor FeCr0.02_{0.02}Se

We report the growth and characterization of single crystals of iron chalcogenide superconductor FeCr$_{0.02}$Se. There is an enhancement of the superconducting transition temperature (T$_{\rm c}$) as compared to the T$_{\rm c}$ of the single crystals of the parent compound Fe$_{1+x}$Se by about 25%. The superconducting parameters such as the critical fields, coherence length, penetration depth and the Ginzburg-Landau parameter have been estimated for these single crystals. Analysis of the critical current data suggests a fluctuation in electronic mean free path induced ($\delta l$) pinning mechanism in this material. Thermally activated transport across the superconducting transition in the presence of external magnetic fields suggests a crossover from a single vortex pinning regime at low fields to a collective flux creep regime at higher magnetic fields. The nature of charge carriers in the normal state estimated from the Hall effect and thermal transport measurements could provide crucial information on the mechanism of superconductivity in Fe-based materials.Comment: 2 additional figures, additional discussion on nature of charge carrier

A Review on Parenteral Production Technology

The main objective of this paper is to facilitate the area planning, utilities, environmental control for production of parenteral. Compare to other dosage forms parenterals are efficient. This gives quick onset of action and provides a direct route for achieving the drug effect within the body. So by producing these under necessary requirements we can yield better economic and therapeutical performance

Eficácia do látex da Euphorbia hirta como moluscicida vegetal contra caramujos de água doce

Os efeitos tóxicos das combinações binárias e terciárias do pó de látex da Euphorbia hirta Linn assim como outros compostos vegetais moluscicidas foram avaliados em sua ação sobre caramujos de água doce Lymnaea (Radix) acuminata e Indoplanorbis exustus em represas. Estas combinações mostraram significante efeito dose e tempo dependente contra ambos os caramujos. Estes compostos em doses altas foram também letais para peixes de água doce Channa punctatus (Bloch) (Channidae {Ophicephalidae}), que compartilham o ambiente com estes caramujos mas a dose LC90 (24h) para caramujos aparentemente não tem propriedade de matar as populações de peixes quando uma população mista de peixes e caramujos são tratadas.The toxic effect of binary and tertiary combinations of Euphorbia hirta Linn latex powder with other plant molluscicidal compounds, were evaluated against the freshwater snails Lymnaea (Radix) acuminata and Indoplanorbis exustus in pond. These combinations showed significant time and dose dependent effect against both the snails. These compounds at higher doses were also lethal to freshwater fish Channa punctatus (Bloch) (Channidae {Ophicephalidae}), which shares the habitat with these snails, but the LC90 (24h) doses of snails have no apparent killing properties in fish populations when treated in mixed population of snails and fish

Efeitos de combinações unitárias, binárias e terciárias de Jatropha gossypifolia e outros muluscicidas derivados de plantas na reprodução e sobrevivência do caramujo Lymnaea acuminata

The effect of sub-lethal doses (40% and 80% of LC50/24h) of plant derived molluscicides of singly, binary (1:1) and tertiary (1:1:1) combinations of the Rutin, Ellagic acid, Betulin and taraxerol with J. gossypifolia latex, leaf and stem bark powder extracts and their active component on the reproduction of freshwater snail Lymnaea acuminata have been studied. It was observed that the J. gossypifolia latex, stem bark, individual leaf and their combinations with other plant derived active molluscicidal components caused a significant reduction in fecundity, hatchability and survival of young snails. It is believed that sub-lethal exposure of these molluscicides on snail reproduction is a complex process involving more than one factor in reducing the reproductive capacity.O efeito de doses sub-letais (40% e 80% de LC50/24h) de moluscicidas derivados de plantas com combinações unitárias, binárias (1:1) e terciárias (1:1:1) de Rutin, ácido Elágico, Betulin e taraxerol com látex da J. gossypifolia, folhas e extrato em pó de casca de caule e seus componentes ativos foram estudados na reprodução do caramujo de água fresca Lymnaea acuminata. Foi observado que o látex da J. gossypifolia, casca do caule, folhas individualmente e suas combinações com componentes moluscicidas ativos derivados de outras plantas causaram redução significante na fecundidade, incubação e sobrevivência dos caramujos jovens. Acredita-se que a exposição sub-letal destes moluscicidas sobre a reprodução dos caramujos é processo complexo envolvendo mais de um fator na redução da capacidade reprodutiva

Analysis of the Performance of IoT Networks in Acoustic Environment by using LZW Data Compression Technique

The Internet of Things (IoT) has experienced phenomenal growth, opening up a wide range of applications in many settings. Due to the properties of sound propagation, IoT networks operating in acoustic environments in particular present special difficulties. Data compression techniques can be used to minimize overhead and maximize resource utilization in these networks to increase performance. The performance of IoT networks in acoustic environments is examined in this study, with a focus on routing overhead, throughput, and typical end-to-end delay. Lempel-Ziv-Welch (LZW) data compression is used to reduce data size and boost communication effectiveness. Three well-known protocols—MQTT, CoAP, and Machine-to-Machine (M2M)—are assessed in relation to acoustic Internet of Things networks. To mimic different acoustic conditions and collect performance metrics, a thorough experimental setup is used. Different network topologies, data speeds, and compression settings are used in the studies to determine how they affect the performance metrics. According to the analysis's findings, all three protocols' routing overhead is greatly decreased by the LZW data compression approach, which enhances network scalability and lowers energy usage. Additionally, the compressed data size has a positive impact on network throughput, allowing for effective data transmission in acoustic contexts with limited resources. Additionally, using LZW compression is seen to minimize the average end-to-end delay, improving real-time communication applications. This study advances knowledge of IoT networks operating in acoustic environments and the effects of data reduction methods on their functionality. The results offer useful information for network engineers and system designers to optimize the performance of IoT networks in similar situations. Additionally, a comparison of the MQTT, CoAP, and M2M protocols' suitability for acoustic IoT deployments is provided, assisting in the choice of protocol for particular application needs