Microanalysis of Alzheimer disease NFT and plaques

Electron probe energy dispersive microanalysis of isolated andin situ neurofibrillary tangles (NFT) and neuritic (senile) plaque cores have been done to investigate the levels of Al, Si, Ca and Fe in the leading lesions of Alzheimer disease neuropathology. Varying levels of Si and Al, and to a lesser extent Ca, have been co-localized in about one half of the NFT and plaques examined using X-ray mapping. The variability of detection and the low levels of Al present indicates that aluminum is not required for the formation of the NFT and that aluminosilicates are not involved in the formation of the plaque core.     

Microprobe studies of aluminum accumulation in association with human central nervous system disease

The neurofibrillary tangle, first described by Alzheimer in 1907, along with the senile plaque, represent the two principle neuropathologic lesions identified in the brains of patients with Alzheimer's disease. Aluminum salts inoculated into the central nervous system of certain experimental animals induces neurofilamentous lesions which are similar, but not identical to the neurofibrillary tangles seen in Alzheimer's disease. Although some reports provide evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Over the past several years we have approached this problem using a variety of microprobe techniques in order to determine the distribution of trace elements within individual nerve cells.Using scanning electron microscopy with X-ray spectrometry, we have identified accumulations of aluminum in the neurofibrillary tangle-bearing neurons of cases of Alzheimer's disease. Similar accumulations have been found in the brains of the indigenous natives of Guam who suffer from parkinsonism with dementia and from amyotrophic lateral sclerosis. Recent studies using laser microprobe mass analysis suggest that the predominance of aluminum identified within the parikaryon of neurofibrillary tangle-bearing neurons is located within the neurofibrillary tangle itself. Although this ongoing research still cannot ascribe a causal role for aluminum in the etiology and/or pathogenesis of the neurofibrillary tangle, the data suggest that certain environmental factors related to trace elemental constituents may play an important role in the formation of this type of cellular pathology.     

Models of environmentally induced neurological disease: epidemiology and etiology of amyotrophic lateral sclerosis and parkinsonism-dementia in the Western Pacific

Amyotrophic lateral sclerosis (ALS) on Guam previously attained incidence rates 50 to 100 times that of the continental United States and Europe and accounted for one in five deaths among Chamorros over age 25. A second neurological disorder in high incidence, parkinsonism-dementia (PD), and the early appearance in those populations of neurofibrillary tangles such as are seen in Alzheimer's disease and normal ageing have also been noted. Incidence and mortality rates of both diseases have declined dramatically during the past 30 years, and today, the risk of developing either disease among Guamanian Chamorros is only several times higher than in non-Guamanian populations. The decline is most likely a consequence of increased acculturation over the past three decades, with a concomitant decrease in isolation, changes in dietary habits and local water supplies, and much less dependence on locally grown foodstuffs. Similar declines are evident in the remaining two Pacific foci of high- incidence ALS, namely the Kii Peninsula focus in Japan and southern West New Guinea where western contact and introduction of new foodstuffs have occurred.The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect, provoked by chronic nutritional deficiencies of calcium, lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD. This elemental deposition is thought to result in aberrant microtubule assembly and/or abnormal post-translational modification of the amyloid precursor protein leading to widespread formation of neurofibrillary tangles, the hallmark pathological features in these disorders. The naturalistic paradigms of these foci in the Western Pacific have provided insights to understanding not only ALS and PD but other neurological disorders, such as classical ALS, Parkinson's disease, Alzheimer's disease and early neuronal ageing.     

Microbial transformations in deep-sea sediments: free-vehicle studies

Radiotracer techniques can be used to assess eitherin-situ metabolic activities of natural microbial populations or potential turnover rates of specific substrates under the givenin-situ conditions. The second approach has been used in deep-sea sediment studies where steady-state conditions are unlikely to occur because of the heterogeneous distribution of nutrients as a result of a patchy input by depositing particulates. Recent sediment trap studies have shown that particulate matter reaching the deep sea does contain simple organic compounds. Therefore, the present experiments dealt with the measurement of carbon incorporation and respiration of¹⁴C-labeled acetate, glucose, glutamate and trimethylamine in deepsea sediments. Free vehicles, i.e. aluminum framed tripods that descend untethered to the deep sea floor and return automatically, were used for thein-situ injection and incubation of cores at depths of 2600 to 5330 m. The data were compared to those obtained from (1) parallel samples incubated at 1 atm andin-situ temperature and (2) a shallow-water station (Buzzards Bay, 12 m). Rates measuredin situ generally decrease with water depth as well as with depth in the upper 9 cm of top sediment. In most experiments, rates measured in the 1 atm controls were higher than those observedin situ. This fact supports the general notion that natural populations of deep-sea sediment contain barotolerant and barophilic microorganisms in varying proportions.     

Aluminium and the pathogenesis of senile plaques: studies in Alzheimer's disease and chronic renal failure

Aluminium and silicon are co-localised as aluminosilicate at the centre of the senile plaque core. These focal deposits appear to be a consistent and specific feature associated with A4 amyloid fibrils in the plaque core and are not associated with other types of amyloidosis. A pathogenic role for AI and Si is suggested by the finding of A4 amyloid deposits, immature senile plaques and an abnormal content and distribution of these elements in the brains of patients (<55 years) with chronic renal failure. Evidence suggests that AI uptake and distribution within the brain is mediated by transferrin. The distribution of transferrin receptors may account for the vulnerability of regions such as the hippocampus and cortex which are selectively involved in Alzheimer's disease.     

The central nervous system of Thenus orientalis (Leach)

Previous authors have suggested that there exist close correlations between the topography of the brain and the mode of life in isopods. This paper describes and illustrates the central nervous system of Thenus orientalis (family: Scyllaridae) and evaluates the findings in evolutionary terms. Considering the shortening of the connectives and the fusion of ganglia in the thoracic region of the ventral nerve cord, T. orientalis shows more pronounced marks of specialization than highly evolved isopods; in regard to the topographical displacement of the anatomical units of the brain, it occupies an intermediate position between the primitive Mysidacea and the advanced Isopoda.Present address of the author     

Morphological and histochemical observations on the nervous system of two sipunculid species,Siphonosoma australe and S. cumanense

The nervous systems of Siphonosoma australe Keferstein and S. cumanense Keferstein, 1867 are histologically similar. However, the two species differ with regard to the structure of the nuchal organ and ventral sensory organ. The nuchal organ in S. cumanense is multilobulated, innervated by 4 pairs of nerves and secretes acidophilic granules, whereas that in S. australe is bilobed, innervated by 2 pairs of nerves and is nonsecretory. Whilst the ventral sensory organ in S. cumanense appears empty and collapsed, that in S. australe contains concretions rich in glycoprotein. The central nervous system consists of the cerebral ganglion, circumesophageal commissures, and the ventral medullary nerve cord. The ovoid brain consists of a centrally placed neuropile and a cellular cortex. Three types of neurons are found in the brain: the giant (cyanophil), median (acidophil), and the globular neurons. The cell bodies of the giant and median neurons are located in the posterodorsal part of the brain, whereas the globular neurons predominate in the rest of the cortex. Most of the protein tests stained the giant and median but not globular neurons. The giant neurons also showed a weak PAS and sudanophilic reaction, suggesting the presence of small amounts of neutral mucopolysaccharides and lipids. Cyanophils and acidophils containing fuchsinophilic granules show possible neurosecretory activity.     

Impact of the polychaete Capitella sp. I on microbial activity in an organic-rich marine sediment contaminated with the polycyclic aromatic hydrocarbon fluoranthene

Polychaetes belonging to the genus Capitella are often present in high numbers in organic-rich sediments polluted with, e.g., oil components, and Capitella spp. may have a great impact on the biogeochemistry of these sediments. We examined the influence of Capitella sp. I on microbial activity in an organic-rich marine sediment contaminated with the polycyclic aromatic hydrocarbon, fluoranthene. Capitella sp. I were added to microcosms (10 000 ind m⁻²) and the impact of a pulse-sedimentation of fluoranthene-contaminated sediment (3 mm layer) was studied for a period of 12 d after sedimentation. The sediment oxygen uptake and total sediment metabolism (TCO₂ production) increased in cores with worms (71 to 131%), whereas the anaerobic activity, measured as sulfate reduction rate 12 d after sedimentation, was lower compared to cores without worms. The effect of fluoranthene on sulfate reduction was most pronounced in the presence of worms, with a 34% reduction versus 16% in cores without worms. The reduced sulfur pools in cores with worms were smaller than in cores without worms, suggesting that the reduced anaerobic activity was caused by increased oxidation of the sediment, which may favor O₂ and other electron-acceptors (e.g. NO₃ ⁻, Fe³⁺, Mn⁴⁺) in organic matter decomposition. The sediment oxygen uptake and TCO₂ production did not show significant changes due to fluoranthene treatment, indicating that these parameters were either less sensitive to fluoranthene stress or recovered more rapidly (i.e. within 48 h) than sulfate reduction rates. Bioturbation by Capitella sp. I altered the depth profile of fluoranthene such that fluoranthene was found in deeper sediment layers (down to 2 cm) where diffusional loss and microbial breakdown probably are reduced relative to surface layers. In cores without worms, fluoranthene was found down to 1 cm, with 75% remaining in the upper 5 mm. Received: 5 December 1996 / Accepted: 11 February 1997     

Uptake of aluminum by lipid vesicles

Aluminium uptake and tight binding were studied in multilayered phospholipid liposomes, as a model for cellular uptake of aluminum ions. Most of these studies were conducted with an initial aluminum concentration of 10 μM, while aluminum superficially bound to liposomes was removed by citrate chelation. Maximum uptake and tight binding of aluminium were pH‐dependent. In dimyristoyl phosphatidylcholine (DMPC) liposomes, this maximum occurred in the neutral pH region, while it was shifted towards more acidic pH values in DMPC liposomes containing 20% of acidic phosphatidylserine. The initial rate of aluminum uptake was apparently dependent on the physical state of the liposome membrane. Prior formation of an aluminum‐citrate chelate prevented aluminum uptake and tight binding to DMPC liposomes.     

Single and multiple daily dose toxicokinetics of fluoride after oral administration of sodium fluoride along with aluminum sulfate in goats

Our previous study suggested that toxicokinetic parameters of fluoride were significantly changed on the 30th day as compared with 1st day, after repeated oral administration of sodium fluoride alone for 30 days in goats. The purpose of this study was to investigate whether aluminum sulfate has ameliorative effect on the toxicokinetics of fluoride. For this, sodium fluoride (20 mg kg^?1 b. wt.) along with aluminum sulfate (150 mg kg^?1 b. wt.) was administered in goats for 30 days to investigate its effect on toxicokinetics of fluoride on days 1 and 30. The fluoride levels against time were adequately described by one compartment open model. The peak plasma level of fluoride was observed at 2 h. The toxicokinetics data revealed a nonsignificant decrease in β (elimination rate constant) and C _max (the maximum plasma concentration) and increase in t _1/2 K _a (absorption half-lives), t _1/2 β (elimination half-lives), area under the plasma (AUC) concentration versus time curve and mean residence time (MRT) was observed for the last dose from their respective first dose values. On the basis of changes in the toxicokinetic parameters, it was concluded that repeated oral administration has cumulative effect on plasma fluoride level and concurrent oral administration of aluminum sulfate has ameliorative action on the toxicokinetics of fluoride in goats.     

The multixenobiotic resistance mechanism in the marine sponge Suberites domuncula: its potential applicability for the evaluation of environmental pollution by toxic compounds

Experiments were carried out with the marine sponge Suberites domuncula to determine whether sponges may express-like mammalian tumor cells-a multidrug-like transporter system. The results demonstrate that sponge cells possess such a protective system termed multixenobiotic resistance (MXR) pump or P-glycoprotein-like pump. The protein was identified by antisera for the mammalian P170 multidrug resistance protein as a 130 kDa molecule. Binding studies were performed with ³H-vincristine (³H-VCR) and membrane vesicles; this process is ATP-dependent and inhibited by verapamil, which is known to reverse the multidrug-resistance phenotype in mammalian systems. Accumulation experiments were performed to demonstrate that the uptake of ³H-VCR is time-dependent, and increases at elevated extracellular levels of ³H-VCR. Application of the dyeing technique with calcein-AM, a suitable functional assay for multidrug transporter systems in mammal cells, also revealed the existence of the MXR pump in S. domuncula plasma membranes. These data demonstrate that S. domuncula is provided with a multidrug-like transporter, the MXR pump, which might function as a protection system for sponges in polluted environments.     

Sodium cyanide-induced modulations in the activities of some oxidative enzymes and metabolites in the fingerlings of Cyprinus carpio (Linnaeus)

Carp fingerlings exposed to a sublethal concentration (0.5?mg?L^?1) of sodium cyanide showed a steady decrement over a 7-day period in respiratory rate, rise in lactate dehydrogenase (LDH), and fall in succinate dehydrogenase (SDH) activities followed by variations in lactic and pyruvate levels. Changes in these enzyme activities might be due to impaired oxidative metabolism and severe cellular damage leading to the release of these enzymes. Decline in the activities of SDH and LDH clearly represents a shift from aerobic to anaerobic metabolism as evidenced by elevated lactate and decline in pyruvate levels. The shift to anaerobic metabolism is also reflected by severe drop in the respiratory rate of the fish. This may be a consequence of the blockage of electron transfer from cytochrome c oxidase to molecular oxygen, thus ceasing cellular respiration and it can lead to cellular hypoxia even in the presence of normal hemoglobin oxygenation. Hence, we indirectly reconfirm the inhibition of oxidative metabolism by sodium cyanide. Alterations in behavioral pattern induced by sublethal sodium cyanide exposure may be due to the combination of cytotoxic hypoxia with lactate acidosis, which depresses the central nervous system (CNS); as the brain is the most sensitive site to anoxia, it results in impaired CNS function.     

Biochemical and histopathological changes of Biomphalaria alexandrina snails exposed to bisphenol A

The effects of sub-lethal concentrations of bisphenol A on some biochemical parameters in Biomphalaria alexandrina snail's hemolymph and tissues as well as on histological changes of the hermaphrodite gland were evaluated. Adult snails were exposed to sub-lethal concentrations for four weeks and samples of snails were investigated after two and four weeks. Total protein and albumin levels in hemolymph, as well as lipid peroxidation and glutathione contents of snails’ tissues, were measured. After two weeks of exposure, total protein content and albumin levels decreased in all groups. Elevation of lipid peroxidation levels was correlated with decreasing glutathione content in the treated snails. Histological examination of the hermaphrodite gland revealed deformations in eggs and affected sperm production.     

Quantification of metallothionein in whole body gammarus locusta (crustacea: amphipoda) using differential pulse polarography

A polarographic method was optimised for the quantitative determination of metallothionein (MT) in whole body Gammarus locusta (Crustacea: Amphipoda). The identity of the MT-like proteins was examined using electrophoretic analysis (SDS-PAGE) and induction studies (water-borne exposures to copper). The MT-method was then used to examine changes in MT levels over the lifetime (juveniles, sub-adults and adults) of a laboratory population of G. locusta; copper (Cu) and zinc (Zn) body burden were also measured by flame atomic absorption spectrometry. MT was quantified by heat-denaturation of 30?000?g supernatants (to remove the bulk of non-MT proteins) followed by differential pulse polarography (DPP) to measure sulphydryl-group containing proteins. DPP proved to be a sensitive and reliable method to quantify heat-stable total sulphydryl-proteins. The majority of the latter was indicated to be MT from SDS-PAGE and induction studies. SDS-PAGE revealed a putative MT of 23?±?0.6?kDa app. mol. wt., consistent with the average size of dimeric MTs (10–20?kDa) found in several aquatic invertebrate species. Copper-exposure revealed parallel increases in the amounts of 23?kDa protein and total sulphydryl-proteins. Levels of whole body MT (rabbit pure MT as standard) range between 1.3 and 2.3?mg?g^?1 dry wt. over the lifetime of G. locusta. Sex-related changes in MT status were observed, the levels in females being 1.6 times higher than in males (p<0.05). Copper and Zn body content changed over the lifetime of G. locusta, the levels in juveniles (p>0.05) and sub-adults (p<0.05) being higher than in adults. It is concluded that the inclusion of MT in ecotoxicological studies with amphipod crustaceans require some caution with respect to the stages of moulting and/or sexual maturation of organisms, but this should not provide any major impediment in its use in metal pollution monitoring.     

砷污染土壤中不同基因型水稻根表铁膜的形成及其对砷吸收和转运影响

采用土壤盆栽试验法,研究6个不同基因型水稻品种根表铁膜形成及其对As吸收、转运的影响。结果表明,水稻形成根表铁膜在不同基因型品种之间差异显著（p<0.001）,其中品种94D-22形成铁膜量（以Fe含量计）是品种圭630的1.5~1.8倍,添加As处理对水稻根表铁膜形成影响不显著。低As含量的对照土壤中,水稻根表铁膜量与根系As含量存在着显著的正相关关系（r=0.657,n=24,p<0.01）,与As转移系数呈显著的负相关关系(r=-0.612,n=24,p<0.01）。土壤添加As后,水稻根表铁膜量与茎叶As含量存在显著的正相关关系（r=0.653-0.673,n=24,p<0.01）,与As转运之间无显著相关性。比较生长于As污染土壤的不同水稻品种,科优1360茎叶积累As较少,且其根系转运As能力也较差,而品种94D-22正好相反。研究结果表明,在As含量较低的土壤中,水稻根表铁膜的存在可成为根系As的障碍层,阻止As向地上部转运;但在As含量较高的土壤,根表铁膜的存在却促进了水稻茎叶对As的积累,其对As的转运没有显著影响。人们可通过作物品种筛选来防治土壤As污染危害、降低As对人体健康的威胁。     

Deposit-feeding amphipods (Monoporeia affinis) reduce the recruitment of copepod nauplii from benthic resting eggs in the northern Baltic Sea

We experimentally investigated the effect of different densities of the burrowing, deposit-feeding amphipod Monoporeia affinis on the recruitment of zooplankton from benthic resting eggs. Intact sediment cores with in situ density and species composition of zooplankton resting eggs and benthic fauna were collected in the northern Bothnian Sea, part of the Baltic Sea. We removed as many M. affinis as possible from the cores and then added different numbers of M. affinis to the cores to generate a range of densities. The cores were exposed to different densities of M. affinis for either 3 or 40 days, after which the hatched zooplankton was registered. One subset of the cores were initially incubated under low temperature (2–3 °C, to prevent hatching) for 37 days (the resting phase), to allow for effects of M. affinis on unhatched resting eggs. These cores were then incubated under higher temperature (13 °C) for 3 days (the hatching phase), to induce hatching and allow for effects on hatching or hatched specimens. In a second subset of cores with the same time and temperature schedule, the M. affinis density was experimentally reduced at the start of the hatching phase, to evaluate the effect of M. affinis during the hatching phase. To a third subset of cores, we immediately initiated the hatching phase, without an experimental resting phase, to evaluate the effects induced during the resting phase. The most common zooplankton species that hatched was Eurytemora affinis (Copepoda), followed by Bosmina longispina maritima (Cladocera). In all cores that were subjected to a resting phase, the numbers of hatched E. affinis were log-linearly negatively related to density of M. affinis. An increase of M. affinis density from 1,000 to 5,000 individuals m⁻², normal field densities, reduced the hatching by 60–70%. The negative impact was mainly exerted during the hatching phase, suggesting predation on, burial of or physical injury of hatching nauplii or eggs in a late development stage as likely mechanisms. Also, the number of B. longispina maritima that hatched was reduced by M. affinis during the hatching phase, but no clear relation to density of M. affinis could be identified. The results show that M. affinis can reduce recruitment to zooplankton from benthic resting eggs. Such impact by the benthos on resting stages of zooplankton is therefore a potentially significant link between the benthic and pelagic systems. Received: 10 August 2000 / Accepted: 13 November 2000     

Effects of mussel (Perna canaliculus) biodeposit decomposition on benthic respiration and nutrient fluxes

Suspension-feeding bivalves increase the quantity and quality of sedimenting organic matter through the production of faeces and pseudofaeces that are remineralised in coastal sediments and thus increase sediment oxygen demand and nutrient regeneration. Bivalves are intensively cultivated worldwide; however, no bivalve biodeposit decay rates are available to parameterise models describing the environmental effects of bivalve culture. We examined sediment biogeochemical changes as bivalve biodeposits age by incubating coastal sediments to which we added fresh mussel (Perna canaliculus) biodeposits and measured O₂ and nutrient fluxes as well as sediment characteristics over an 11-day period. Biodeposits elevated organic matter, chlorophyll a, phaeophytin a, organic carbon and nitrogen concentrations in the surface sediments. Sediment oxygen consumption (SOC) increased significantly (P=0.016) by ∼1.5 times to 1,010 μmol m⁻² h⁻¹ immediately after biodeposit addition and remained elevated compared to control cores without additions for the incubation period. This increase is in the range of observed in situ oxygen demand enhancements under mussel farms. To calculate a decay rate for biodeposits in sediments we fitted a first-order G model to the observed increase in SOC. The significant model fit (P=0.001, r ²=0.72) generated a decay rate of 0.16 day⁻¹ (P=0.033, SE=0.05) that corresponds to a half-life time of 4.3 day. This decay rate is 1–2 orders of magnitude higher than published decay rates of coastal sediments without organic enrichment but similar to rates of decaying zooplankton faecal pellets. NH₄⁺ release increased rapidly on the day of biodeposit addition (P=0.013) and reached a maximum of 144 μmol m⁻² h⁻¹ after 5 days which was 3.6 times higher compared to control cores. During this period NH₄⁺ release was significantly (P<0.001 to P=0.043) higher in the cores with biodeposit additions than in control cores.     

大鼠胚胎期PFOS暴露致出生早期死亡及神经系统发育影响的基因组学分析

为了阐明PFOS导致新生儿死亡的可能原因和机制,探讨PFOS致死与神经系统发育的相互联系,利用基因芯片技术,观察了经PFOS饲料染毒后出生1和7d大鼠脑组织基因表达情况,通过基因组学(Gene Ontology)和生物路径(Pathway)对差异基因的功能和相互联系进行分析.结果显示,PFOS染毒后,出生1、7d的大鼠脑皮质组织分别有864、642条基因发生差异表达,差异基因涉及的与PFOS致死相关的生物过程包括中枢神经系统发育、血循环系统、刺激应答、骨骼发育、氧化应激、心脏功能以及pH值调节等.结果表明,PFOS导致的出生早期死亡与神经系统发育有关,PFOS可能通过改变脑组织血氧平衡,影响正常的中枢神经系统功能和发育过程而使新生儿的存活率下降.     

Migration of aluminum from food contact materials to food—a health risk for consumers? Part I of III: exposure to aluminum,release of aluminum,tolerable weekly intake (TWI), toxicological effects of aluminum,study design,and methods

Background

In spite of the prevalence of aluminum in nature, no organism has been found to date which requires this element for its biological functions. The possible health risks to human beings resulting from uptake of aluminum include detrimental effects to the hemopoietic system, the nervous system and bones. Aluminum is used in many fields and occurs in numerous foodstuffs. Food contact materials containing aluminum represent an anthropogenic source of dietary aluminum.

Results

As a result of their frequent use in private households a study was undertaken to detect migration of this metal to foodstuffs from drink containers, coffee pots, grill pans, and camping cookware made of aluminum.

Conclusions

An estimate of the health risk to consumers is calculated, based on the tolerable weekly intake (TWI) specified by the European Food Safety Authority of 1 mg/kg body weight for all groups of people. In some instances the TWI is significantly exceeded, dependent upon the food contact material and the food itself.