The blood-brain barrier restricts the administration of drugs for neurological diseases. K16ApoE is an effective drug delivery carrier to deliver drugs across the blood-brain barrier, but it contains ...acute and high toxicity. The toxicity mechanism of K16ApoE must be revealed for clinical uses. Previous studies hypothesized that the toxicity mechanism was acetylcholinesterase inhibition in the brain. However, these studies used improper buffers in the AChE assay, further leading to anomalous results. Meanwhile, previous studies have not investigated the effects of K16ApoE on all the AChE-containing tissues and organs throughout the body. The previous dose design was also too narrow. Herein, we designed a more comprehensive and rational dose interval for K16ApoE, observed and recorded the mouse responses after receiving K16ApoE, and collected the brain, diaphragm, and serum to investigate the systemic K16ApoE effects on AChE. We also incubated purified AChE with K16ApoE in vitro. It could reveal the direct effect of K16ApoE on AChE without the influence of absorption and metabolism in vivo. The in vitro results demonstrated that K16ApoE inhibits rhAChE activity as the dose increases. However, the in vivo results demonstrated that K16ApoE does not affect tissue AChE activity in female mice. Therefore, we confirmed the AChE inhibitory effect of K16ApoE, but contrary to our hypothesis, AChE inhibition is not the toxicological mechanism of K16ApoE. We also recorded toxicological responses after the mice received K16ApoE, which would promote further toxicological investigation on K16ApoE.
K16ApoE is a brain-targeted drug carrier that can deliver drugs throughout the brain and maintain sustained activity during delivery. However, related studies have revealed that K16ApoE has acute and ...high toxicity, and its toxicological mechanism remains unknown. Our previous experiments found that K16ApoE affects the blood state of mice. Thus, we performed a hemolysis assay to investigate whether K16ApoE could induce hemolysis, but we found that K16ApoE was unable to lyse red blood cells at lethal doses. Then, we monitored cerebral blood flow and perfusion after the mice received incremental doses of K16ApoE and found that K16ApoE could suddenly interrupt the blood flow and reduce the perfusion in the brain. K16ApoE could also disrupt the consistency of cerebral perfusion. Last, we examined the blood cells under the microscope and found that K16ApoE caused the cells to clump in the plasma and increase blood viscosity. Based on these findings, we confirmed that the toxicity of K16ApoE is mainly in the blood. The mechanism is that K16ApoE induces blood cell aggregation and interrupts blood flow.
Between 27 August 2011 and 15 September 2011, the Hudson River Estuary was subjected to two named weather events: Hurricane Irene and Tropical Storm Lee. An ongoing sampling programme enabled the ...collection of pre-storm, post-storm and prior year data of physical, chemical and biological parameters at eight locations within or adjacent to the Estuary, including the upper Hudson River and the Mohawk River. Samples were analysed to determine the degree of impact by Hurricane Irene and Tropical Storm Lee. Suspended solids and water clarity showed significant changes, particularly at the confluence of the Mohawk River. Total phosphorus, pH and conductivity were all significantly different following the storms, but no identifiable change to total nitrogen occurred. Physical parameters associated with the Mohawk River were different pre- and post-storm, but most chemical parameters remained unchanged. Sample locations within the Estuary showed changes to both physical and chemical parameters. Estuary-wide, chlorophyll a concentration and zooplankton density biota were significantly reduced. The data indicate that quantified impacts to water quality lasted for up to three months. An assessment of these results leads to the conclusion that anthropogenic influences within and surrounding the Estuary exacerbated the ecological impacts of these storms.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Traditional Chinese medicine has usually been recognized to be efficacious to treat chronic diseases from the western point-of-view. However, there is a long history in China of applying traditional ...Chinese medicine in many acute and urgent medical conditions. In this review, selected methods documented in traditional Chinese medicine including blowing air to ear, nose insufflating therapy, acupuncture and moxibustion were presented as the common practices to promote consciousness recovery from coma. We aimed to explore the mechanism of these four methods with current scientific evidence, further discuss the potential of traditional Chinese medicine to be applied in emergency medicine and provide a path forward to more rigorously validate these procedures. The development of the integrated traditional Chinese medicine and western medicines provides a new therapeutic direction for the new first-aid treatment.
The K16ApoE peptide has been demonstrated to deliver a supraphysiological level of protein therapeutics to the brain and further increase the life-span of mice with a lysosomal storage disorder ...(LSD). If successfully developed, K16ApoE would provide new treatments for LSD and many other neurological diseases. However, while the K16ApoE can cross the blood-brain barrier, data indicates a toxic response associated with it. The mechanism of toxicity must be resolved for further clinical translation. The toxic response towards the peptide was hypothesized to be induced by inhibition of acetylcholinesterase (AChE) activity at neuro-muscular junction. Here, the dose-response analysis between AChE and K16ApoE was conducted in both female and male mice. Results demonstrated that AChE activity was significantly reduced with increasing dose of K16ApoE except for the mid-dose where a dramatic increase in AChE activity was observed. Also, obvious difference in response to K16ApoE was shown when considering the influence from sex and body weight. Though the statistical analysis of the dose response and survival ratio suggested that AChE is not the primary mechanism of action for the acute toxicity of K16ApoE, the complex inhibition/stimulation response of AChE indicated that this enzyme must play a role in the toxicity of the peptide.
In 1990, the US Congress amended the Clean Air Act (CAA) to reduce regional-scale ecosystem degradation from SO
x
and NO
x
emissions which have been responsible for acid deposition in regions such as ...the Adirondack Mountains of New York State. An ecosystem assessment project was conducted from 1994 to 2012 by the Darrin Fresh Water Institute to determine the effect of these emission reduction policies on aquatic systems. The project investigated water chemistry and biota in 30 Adirondack lakes and ponded waters. Although regulatory changes made in response to the 1990 CAA amendments resulted in a reduction of acid deposition within the Adirondacks, the ecosystem response to these reductions is complicated. A statistical analysis of SO
4
, pH, Al, and DOC data collected during this project demonstrates positive change in response to decreased deposition. The changes in water chemistry also have lowered the risk of Al toxicity to brook trout (
Salvelinus fontinalis
Mitchill), which allowed the re-introduction of this species to Brooktrout Lake from which it had been extirpated. However, pH and labile aluminum (Al
im
) fluctuate and are not strongly correlated to changes in acid deposition. As such, toxicity to
S. fontinalis
also is cyclic and provides rationale for the difficulties inherent in re-establishing resident populations in impacted aquatic environments. Overall, aquatic ecosystems of the Adirondacks show a positive response to reduced deposition driven by changes in environmental policy, but the response is more complex and indicates an ecosystem-wide interaction between aquatic and watershed components of the ecosystem.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Concurrent regional and global environmental changes are affecting freshwater ecosystems. Decadal-scale data on lake ecosystems that can describe processes affected by these changes are important as ...multiple stressors often interact to alter the trajectory of key ecological phenomena in complex ways. Due to the practical challenges associated with long-term data collections, the majority of existing long-term data sets focus on only a small number of lakes or few response variables. Here we present physical, chemical, and biological data from 28 lakes in the Adirondack Mountains of northern New York State. These data span the period from 1994-2012 and harmonize multiple open and as-yet unpublished data sources. The dataset creation is reproducible and transparent; R code and all original files used to create the dataset are provided in an appendix. This dataset will be useful for examining ecological change in lakes undergoing multiple stressors.
We collected statoblasts of the bryozoans Pectinatella magnifica, Lophopodella carteri, and Cristatella mucedo from multiple locations within the Hudson River Estuary and at the confluence of the ...Mohawk and the Hudson Rivers during benthic invertebrate sampling activities October 2009-November 2011. We identified both P. magnifica and L. carteri at geographically separated locations within the estuary. Although these animals are exclusively freshwater organisms, we found P. magnifica and L. carteri statoblasts in both freshwater and brackish water environments; only P. magnifica is considered indigenous to New York. Based upon the distribution of statoblasts, it is unknown whether C. mucedo is resident in the estuary. However, our findings indicate that the estuary and the Mohawk River have established populations of L. carteri and P. magnifica.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Hudson River Estuary (Estuary) is a 245 km (154 mi) long water body located in eastern New York State. It is the central geographic feature of an important ecological, economic and cultural ...region. As such, the Estuary has been the subject of a significant number of scientific investigations addressing various biotic and abiotic components of this ecosystem. However, most of this work has addressed the mainstem of the Estuary with considerably less work focusing on the near-shore embayments surrounding the confluence of tributaries to the Estuary. This project investigated biologic implications of pesticide policy on the Estuary focusing on the areas of confluence between tributaries and the Estuary. The results demonstrate that the areas surrounding the confluence of these tributaries are unique ecosystems that are structurally different from each other and vary both by location within the Estuary and the time of year. Significant differences occur in both the biotic and abiotic components of the ecosystems studied. To assess the potential impacts pesticides may have on these ecosystems, a bioaccumulation model was developed to predict the bioaccumulation of organophosphate and carbamate pesticides in the Banded Killifish (Fundulus diaphanus), a euryhaline species found throughout the Estuary. The bioaccumulation model was populated with ecosystem specific data and used to determine if F. diaphanus is exposed to different concentrations of pesticides based on location within the Estuary. The data conclusively demonstrate that variation within the investigated ecosystems results in significantly different pesticide body burden in F. diaphanus. The body burden differences have a mixed correlation with activity rates of acetylcholinesterase, an enzyme of the neurological system inhibited by organophosphate and carbamate pesticides. Overall, the pesticide policies applied throughout the Estuary do not prevent the bioaccumulation of pesticides within the Estuary. The model utilized in this project demonstrates that pesticide concentrations in the environment, while low, have the potential to bioaccumulate to levels that can result in biological effects.
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