Thesis (MScAgric)--University of Stellenbosch, 2005. / ENGLISH ABSTRACT: Conyza bonariensis (flaxleaf fleabane) was reported for the first time, as a weed in California in 1893-1896. The first report of the occurrence of this weed in South Africa was made in May 1895 in Franschoek, South Africa. Paraquat resistance in C. bonariensis was first reported in the 1970s and early 1980s when resistance was observed from vineyards and citrus plantations in Egypt. More recently a report of herbicide resistance in South Africa was made in January 2003 when resistance occurred in C. bonariensis in the Breede Valley, South Africa. The resistance was to glyphosate, but recently reports of resistance to glyphosate and paraquat were received. C. bonariensis seeds were found to be positively photoblastic and germinated only under unfiltered white light and red light whilst no germination occurred under far-red light and in the dark. The optimum temperature range for C. bonariensis seed was found to be between 15 and 30°C, with no germination occurring at 0-5°C and at 35- 40°C. Optimum germination occurred at the soil surface. No germination occurred at depths of 2 cm and deeper. Although the optimum temperature range was found to be the same for the different biotypes tested. However, germination was highest in the susceptible biotype. Since farmers first reported paraquat and glyphosate resistance in C. bonariensis in the Breede Valley, South Africa, reports of resistance increase every year. Seed collected from populations suspected of being resistant to paraquat and glyphosate were obtained from the Breede Valley and screened for resistance. To determine the easiest, quickest, and most effective method to screen for paraquat and glyphosate resistance, two tests were evaluated viz. the petri dish assay method and the whoIeplant dose-response method. Both screening methods identified paraquat and glyphosate resistant biotypes. The petri dish assay method was found to be a more rapid method of screening for resistance in C. bonariensis. During this study it was found that both paraquat and glyphosate resistance does occur in the Breede Valley. The effect of growth stage on the level of herbicide resistance in C. bonariensis was tested. Herbicides other than paraquat and glyphosate were tested to determine if they could be used to control resistant C. bonariensis seedlings. The alternative herbicides tested included MCPA and Sorgomil Gold 600. The four herbicides were sprayed at different leaf stages. During the study it was found that growth stage does play an important role in the level of herbicide resistance. It was found that the control of different herbicides decreased with an increase in growth stage. The different herbicides showed varying levels of control depending on growth stage and resistant profile. Overall MCPA gave the best control at all leaf stages tested. What is gratifying was the finding that every biotype tested could be controlled by at least one of the treatments applied. This means that the producer using the most appropriate herbicide applied at the optimum application stage will be able to control most if not all the resistant populations of C. bonariensis that occur in the Western Cape. / AFRIKAANSE OPSOMMING: Conyza bonariensis (Kleinskraalhans) is vir die eerste keer as 'n onkruid gerapporteer in Kalifornia in 1893-1896. Die eerste waarneming van hierdie onkruid in Suid-Afrika is gemaak in Mei 189S in Franschoek. Parakwat weerstandbiedendheid in C. bonariensis is die eerste maal in die 1970s en vroeë 1980s waargeneem, toe weerstandbiedendheid opgemerk is in wingerde en sitrus plantasies in Egipte. Meer onlangs is 'n geval van onkruiddoder weerstandbiedendheid in Suid-Afrika aangemeld in Januarie 2003, toe 'n biotipe van C. bonariensis in die Breede Vallei weerstand-biedendheid getoon het teen 'n onkruiddoder. Die weerstand was teen glifosaat, maar onlangse berigte van weerstandbiedendheid teen glifosaat sowel as parakwat is ontvang. Daar is gevind dat die saadjies van C. bonariensis positief fotoblasties is en slegs ontkiem onder ongefiltreerde wit- en rooi lig, terwyl geen ontkieming voorkom onder ver-rooi lig en in die donker nie. Die optimum temperatuurreeks vir C. bonariensis saad is tussen IS en 30°C, met geen ontkieming wat by O-SoCen by 3S-40°C voorkom nie. Optimum ontkieming kom voor op die grondoppervlak. Geen ontkieming kom by dieptes van 2 cm of dieper voor nie. Alhoewel die optimum temperatuurreeks dieselfde is vir die verskillende biotipes wat getoets is, is daar tog 'n verskil in die persentasie ontkieming tussen die biotipes met die beste ontieming by die sensitiewe biotipe. Sedert boere die eerste geval van parakwat en glifosaat weerstandbiedendheid in C. bonariensis in die Breede Vallei, Suid-Afrika gerapporteer het, word meer gevalle van weerstandbiedendheid jaarliks aangemeld. Saad van populasies wat vermoedelik parakwat en glifosaat weerstandbiedend is, is in die Breede Vallei versamel en getoets vir weerstandbiedendheid. Om die maklikste, vinnigste en mees effektiewe metode van weerstandbiedendheidstoetsing te vind, is twee verskillende metodes van toetsing, naamlik die petribakkietoets en die heel plant dosis respons metode gebruik. Beide metodes van toetsing het parakwat en glifosaat weerstandbiedende biotipes geïdentifiseer. Daar is gevind dat die petri bakkie metode 'n vinniger manier van toetsing vir weerstandbiedendheid is. Die studie het ook bewys dat parakwat en glifosaat weerstandbiedendheid wel in die Breede Vallei, Suid-Afrika voorkom. Die effek van groeistadium op die vlak van onkruiddoder weerstandbiedendheid in C. bonariensis is ook tydens die studie getoets. Ander onkruiddoders buiten parakwat en glifosaat is getoets om te bepaal of hulle gebruik kan word vir die effektiewe beheer van weerstandbiedende C. bonariensis saailinge. Die alternatiewe onkruiddoders wat getoets is, was MCPA en Sorgomil Gold 600. Die vier onkruiddoders is gespuit by verskillende blaarstadiums. Gedurende die studie is daar gevind dat groeistadium wel 'n belangrike rol speel in die vlak van onkruiddoder weerstandbiedendheid. Die persentasie beheer van verskillende onkruiddoders neem af met 'n toename in die groeistadium. Die verskillende onkruiddoders se beheer het gewissel afhangend van weerstandbiedendheid en groeistadium. MCPA het die beste beheer by alle blaarstadiums wat getoets is getoon. Daar is ook gevind dat een of die ander van die onkruiddoders wat getoets is, gebruik kan word vir die suksesvolle beheer van onkruiddoder weerstandbiedendheid in elke biotipe wat getoets is. Dit beteken dat 'n produsent wat die korrekte onkruiddoder op die korrekte groeistadium toedien, in staat sal wees om die meeste, indien nie alle weestandbiedende C. bonariensis populasies wat in die Wes Kaap voorkom, te beheer.

帕金森氏症 (Parkinson’s disease，PD) 為目前最普遍的神經退化性疾病之一，該病因主要是由於中腦黑質區的多巴胺細胞的死亡造成運動系統的失能。環境常用農藥百草枯 (Paraquat，PQ) 目前已知是導致帕金森氏症的環境因子之一。它主要作用在粒線體上，阻斷粒線體的功能、造成大量氧化自由基生成、並誘導細胞凋亡的發生。沉默調節因子蛋白Sirtuin家族 (Sirtuin Family，Sirt1-Sirt7) 是一群 Nicotinamide adenine dinucleotide (NAD+) 依賴性去乙醯化酶，具有抗老化、以及預防神經退化性疾病等能力。SRT1720是根據天然植物酚類白藜蘆醇製造出來的化學衍生物，具有活化Sirtuin的能力。先前研究也顯示SRT1720具有增加糖尿病小鼠的存活率、抗腫瘤、抗發炎等功能，但SRT1720對於神經退化性疾病的保護性並不清楚。為了解SRT1720是否具有對抗PQ的細胞毒性，用以評估SRT1720是否具有治療帕金森氏症的潛力，本研究使用人類神經瘤母細胞株 (SH-SY5Y) 作為帕金森氏症的離體外實驗模式，來探討SRT1720及PQ對於細胞的作用及影響。實驗結果顯示，PQ造成細胞存活率呈劑量反應地下降，而SRT1720可以回復因PQ所造成細胞存活率的下降、細胞凋亡的產生、粒線體的型態變化，以及降低氧化自由基的生成等。這證明SRT1720對細胞具有神經保護的效果。本研究也利用西方點墨法證實了當細胞暴露在PQ下，SRT1720會回復因PQ所導致Sirt1-Sirt7蛋白含量的下降。其中，大量表現Sirt1可以對抗PQ造成細胞的死亡。本研究也發現SRT1720可回復PQ自噬小體在細胞中的堆積情形，利用西方點墨法觀察SRT1720可以回復LC3-I/II的蛋白質再細胞間的堆積。此外，在對於20週大的C57BL/6小鼠注射PQ (10 mg/kg) 及SRT1720 (0.1mg/kg或1 mg/kg)，並利用滾輪及獨木橋試驗觀察其運動行為。結果顯示，SRT1720可以回復PQ所造成運動能力上的下降，並且減緩PQ所造成中腦區多巴胺神經元的傷害。綜觀以上結果，在細胞暴露在PQ時，SRT1720或許可以經由保護粒線體功能，使ROS生成量達到回復及降低細胞凋亡的發生。同時SRT1720也能保持自噬作用的平衡，降低自噬小體在細胞中的堆積。這些機轉也許與SRT1720可以保護多巴胺神經元有關。另一方面，由於Peroxisomal proliferator-activated receptor-coactivator 1α (PGC-1α) 與粒線體的生合成與神經保護有關，本實驗也發現SRT1720可改變PGC-1α去乙醯化的程度，但SRT1720對於Sirtuin蛋白以及Sirt1下游PGC-1α的活化與否還需做進一步的調查及研究。此研究顯示SRT1720對於保護細胞免於受到PQ所引發氧化壓力以及粒線體損傷之神經退化模型提供了一個具有潛力的治療方法。 / Parkinson’s disease (PD) is one of the most common neurodegenerative disorder and mainly affecting the motor system because of the dopamine neuronal death in the substantia nigra. The exposure to environmental neurotoxin paraquat (PQ) is a widely used herbicide. It induces the increase of ROS stress, leads to mitochondrial dysfunction, and results in apoptotic cell death. Epidemiologically, it could be the risk for PD incidence. Mammalian silent information regulator 2 Sirtuin Family (Sirt1-Sirt7) is a NAD+ dependent deacetylase enzyme and it protects against such as anti-aging and neurodegenerative disease. SRT1720 which derives from resveratrol is able to activate Sirt1. SRT1720 has been reported to improve survival in obese mice, anti-tumor, and anti-inflammatory, but the effect in the neurodegenerative disease it still unknown. We thus proposed if SRT1720 could have neuron- protective effect in PQ-induced toxicity. We used SH-SY5Y cell to evaluate the effect of SRT1720 and PQ. First, we confirmed that PQ could dose- and time-dependently decrease SH-SY5Y cell viability, increase ROS formation, and induce mitochondrial dysfunction. However, SRT1720 pretreatment improved cell viability, decreased apoptosis and ROS formation, and prevented mitochondrial dysfunction in PQ-treated SH-SY5Y cells. By Western blot analysis, SRT1720 pretreatment could preserve Sirt1-Sirt7 protein contents during PQ intoxication. In autophagy studies, we also found that SRT1720 could reduce PQ-induce autophagic vacuoles accumulation. Furthermore, we also found that intraperitoneally injection of 10 mg/kg PQ once a week in mice can decrease the level of motor activity after 6 weeks treatment. However, SRT1720 (0.1 mg/kg or 1mg/kg) treatment, reversed PQ- induced motor defect. Taken together, SRT1720 could protect mitochondrial function and improve cell survival during PQ intoxication. This work provided a promising therapeutic way for treating aging-related neurodegenerations, such as PD.

<p>U ovom radu je ispitivan uticaj Antitoksičnognutritiva(ATN), preparata na bazi prirodnih aluminosilikata,na biohemijske, fiziolo&scaron;ke, tehnolo&scaron;ke i proizvodne parametre uzgoja pilića. ATN je sme&scaron;a zeolita klinoptilolita, gline monmorilonita i male količine aktivnog uglja. Dodatak ovog preparata u hranivo za piliće u količini od 5 g/kg nije izazvao promene u normalnoj biohemijskoj i fiziolo&scaron;koj homeostazi životinja. Hematolo&scaron;ki parametri, koncentracija metabolita, elektrolita i aktivnost enzima seruma i jetre je bila u granicama referentnih vrednosti. ATN ne utiče na prirast životinja, ni na konverziju hrane, ali dovodi do povećanja relativnih masa pojedinih organa digestivnog trakta.</p><p>Uočava se da dodatkom ATN-a u hranivo dolazi do smanjenja količine masti a povećanja količine proteina u belom mesu. ATN takođe povećava i sadržaj pepela u<br />belom i crvenom mesu.</p><p>Akutni ili hronični tronedeljni oralni unos pojedinih toksikanata (mikotoksina aflatoksina B1i ohratoksina A, herbicida parakvata, jona olova ili toksina<br />cijanobakterija-mikrocistisa) dovodi do poremećaja normalne biohemijske i fiziolo&scaron;ke homeostaze pojedinih organa i tkiva pilića, &scaron;to je utvrđeno na osnovu rezultata hematolo&scaron;kih i biohemijskih analiza, određivanja enzima antioksidativne za&scaron;tite i lipidne&nbsp;<br />peroksidacije, kao i odredjivanja parametara uzgoja i težine organa. ATN, dodat u hranu u količini od 5 g/kg, mogao da bude dobar protektivni agens za delovanje aflatoksina, parakvata, jona te&scaron;kih metala i mikrocistisa, ali ne i ohratoksina.</p> / <p>This study investigated the effects of dietary supplementation with hydrated aluminosilicate (Antitoxic Nutrient-ATN), based on zeolitic ore (clinoptilolite), clay bentonite (montmorillonite),and small amounts of activated charcoal, on&nbsp; performance, hematological, serum, and liver biochemical parameters, as well as organ weights and meat quality in broiler chickens. The dietary addition of ATN has&nbsp; no adverse effects on serum and liver biochemical parameters and does not affect the normal physiological homeostasis of animals. However, the results of this study demonstrate that supplementation with 5 g/kg of ATN influenced organ weights, and chemical composition of broiler chicken meat.</p><p>This study also evaluated the effectiveness of ATN to protect broilers from adverse effects of five different toxic substances (mycotoxins aflatoxin B1, and ochratoxin A, herbicide paraquat, heavy metal ions supplied as lead-acetate, and microcystis, toxin of cyanobacteria). Toxic substances induced oxidative stress and disturb normal biochemical and physiological homeostasis of different tissues and organs in poultry. The results from this study demonstrate that the biochemical variables of serum, liver, kidney, lung and other organs were negatively affected by all five toxic substances. The additionof 5 g/kg of ATN was protective against aflatoxin B1, lead-acetate, paraquat and microcystis, but not against ochratoxin A.</p>

雙酚化合物在文獻報導中發現具有抗發炎和抗氧化的能力，因為其親脂性的特性，雙酚化合物可以輕易穿透血腦屏障到中樞神經系統發揮其藥理活性。因此，雙酚化合物被評估可做為潛在預防及治療神經退化性疾病如帕金森氏症的神經保護藥物。本研究目的為探討新合成的雙酚化合物MH101及MH102是否具有神經保護和治療效用，而對抗神經毒素(包含巴拉圭、過氧化氫及MPTP)引起的神經毒害及其誘發的動物行為異常(如: 學習、記憶及運動協調)。研究中應用Oregon-R的果蠅(年齡: 1-2, 7, 20 和 30天)做為檢測模式，果蠅暴露在巴拉圭 (5-20 mM)或過氧化氫(0.3 %-3 %)環境下，並且給予MH101 (0.1-3 μM)。結果顯示MH101未能有效地減緩巴拉圭及過氧化氫所引起果蠅壽命的下降。此外，給予雄性ICR小鼠 (25-30 g) 腹腔注射MPTP (25mg/kg)每天一次連續五天，觀察神經毒素誘發的行為異常和神經毒害。在觀察保護效果的研究中，雄性小鼠在給予MPTP前一小時腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg) 每天一次連續五天，之後單獨給予MH101或MH102治療連續九天。後處理的組別，雄性小鼠在給予MPTP每天一次連續五天後，每天腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg)連續九天。控制組組別，小鼠則給予生理食鹽水(0.9%)及玉米油的混合液。結果顯示，MH101、MH102及MPTP皆不影響小鼠橫桿行走試驗的運動平衡和協調能力。然而，在前處理和後處理MH101或MH102後用新位置辨識能力測試和新物體辨識能力測試觀察MPTP引起的認知缺失，實驗結果顯示MH101及MH102皆恢復短期記憶和長期記憶的認知辨識指標。另外，前處理和後處理MH101或MH102雖有些微恢復紋狀體內MPTP引起多巴胺神經損傷及多巴胺轉運子減少的趨勢，但不顯著。由此推論，雙酚化合物MH101及MH102具有預防及改善神經毒素所引發的認知與學習缺陷，未來可能發展成為神經退化性疾病如帕金森氏症之潛力治療藥物，另針對MH101及MH102在神經損傷及動物行為障礙的恢復和保護藥理機制則需進一步實驗探討。 / Biphenols which are the main constituents of the traditional herbs have been found to possess the antiinflammatory and antioxidative properties. Due to the lipophilic activity, biphenols can readily cross the blood brain barrier to exert their pharmacological effects in the central nervous system. Thus, biphenols are proposed to act as the novel neuroprotective agents for treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether the new synthetic biphenolic compounds MH101 and MH102 have the neuroprotective and therapeutic actions against the neurotoxicity and the behavioral impairments (e.g. learning, memory, and motor coordination) induced by neurotoxins including paraquat, hydrogen peroxide, and MPTP in PD-like animal models. The following experiments examined the lifespan of flies from Oregon-R strain of Drosophoila melanogaster (age: 1-2, 7, 20 and 30 days) chronically exposed to paraquat (5-20 mM) or hydrogen peroxide (0.3 %-3 %) under MH101 (0.1-3 μM) treatment. Our results showed that MH101 could not effectively influence the reduced lifespan of the flies induced by paraquat and hydrogen peroxide. Furthermore, male ICR mice (25-30 g) were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neuronal damage and cognitive deficits. For the protective study, male mice were administrated with MH101 (1-3 mg/kg, i.p.) or MH102 (0.1-3 mg/kg, i.p.) 1 hour prior to MPTP injection once daily for 5 days, and followed daily treatment with MH101 or MH102 alone for consecutive 9 days after the final injection of MPTP. For the post-treatment study, male mice were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days, and followed by daily treatment of MH101 or MH102 for 9 days. Mice in control group were injected with vehicle (0.9% saline + corn oil). The results showed that MH101, MH102, and MPTP alone did not alter the motor functions of coordination and balance in beam walking test. On the other hand, both pre-treatment and post-treatment of MH101 and MH102 reversed the cognitive dysfunction induced by MPTP detected by novel location recognition test (NLRT) and novel object recognition test (NORT). Data demonstrated that MH101 and MH102 reversed the reduction in recognition index (RI) of short term memory and long term memory in MPTP-induced PD model. However, pre-treatment and post-treatment of MH101 or MH102 slightly recovered MPTP-induced loss of dopamine neurons and dopamine transporter in striatum. Therefore, the results suggest that biphenols including MH101 and MH102 may be the candidates for treatment of neurodegenerative diseases such as PD. In the future, it will need further study to determine the pharmacological mechanism of MH101 and MH102 in protection and restoration of neuronal injury and cognitive impairment.

Neurotoxlns represent unique chemical tools, providing a means to 1) gain insight into cellular mechanisms of apopotosis and necrosis, 2) achieve a morphological template for studies otherwise unattainable, 3) specifically produce a singular phenotype of denervation, and 4) provide the starting point to delve into processes and mechanisms of nerve regeneration and sprouting. There are many other notable uses of neurotoxins in neuroscience research, and ever more being discovered each year. The objective of this review paper is to highlight the broad areas of neuroscience in which neurotoxins and neurotoxicity mechanism come into play. This shifts the focus away from neurotoxins per se, and onto the major problems under study today. Neurotoxins broadly defined are used to explore neurodegenerative disorders, psychiatric disorders and substance use disorders. Neurotoxic mechanisms relating to protein aggregates are indigenous to Alzheimer disease, Parkinson's disease. NeuroAIDS is a disorder in which microglia and macrophages have enormous import. The gap between the immune system and nervous system has been bridged, as neuroinflammation is now considered to be part of the neurodegenerative process. Related mechanisms now arise in the process of neurogenesis. Accordingly, the entire spectrum of neuroscience is within the purview of neurotoxins and neurotoxicity mechanisms. Highlights on discoveries in the areas noted, and on selective neurotoxins, are included, mainly from the past 2 to 3 years.

Neurotoxins, in the general sense, represent novel chemical structures which when administered in vivo or in vitro, are capable of producing neuronal damage or neurodegeneration - with some degree of specificity relating to neuronal phenotype or populations of neurons with specific characteristics (.e., receptor type, ion channel type, astrocyte-dependence, etc.). The broader term 'neurotoxin' includes this categorization but extends the term to include intra- or extracellular mediators involved in the neurodegenerative event, including necrotic and apoptotic factors. Moreover, as it is recognized that astrocytes are essential supportive satellite cells for neurons, and because damage to these cells ultimately affects neuronal function, the term 'neurotoxin' might reasonably be extended to include those chemical species which also adversely affect astrocytes. This review is intended to highlight developments that have occurred in the field of 'neurotoxins' during the past 5 years, including MPTP/MPP+, 6-hydroxydopamine (6-OHDA), meth-amphetamine; salsolinol; leukoaminochrome-o-semi-quinone; rotenone; iron; paraquat; HPP+; veratridine; soman; glutamate; kainate; 3-nitropropionic acid; peroxynitrite anion; and metals (copper, manganese, lead, mercury). Neurotoxins represent tools to help elucidate intra- and extra-cellular processes involved in neuronal necrosis and apoptosis, so that drugs can be developed towards targets that interrupt the processes leading towards neuronal death.

No description available.