China
Africa
Explore chapters and articles related to this topic
The No-Reflow Phenomenon: A Misnomer?
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
Lewis C. Becker, Giuseppe Ambrosio, John Manissi, Harlan F. Weisman
Tissue specimens were then taken for blood flow measurements and electron microscopic examination. Specimens were removed under UV light from either thioflavin-positive or thioflavin-negative areas within the risk region as well as from the nonischemic myocardium in the anterior wall. Care was taken to avoid samples that showed visible heterogeneity in thioflavin staining. The size of the samples was about 50 to 100 mg. The specimens were cut into 2- to 3-mm3 pieces, weighed, and stored in cold (4°C) glutaraldehyde. Microsphere radioactivity was measured and the samples were processed for electron microscopy. Additional samples of the same size were also taken from various zones and counted for regional blood flow measurement.
Radiochemistry for Preclinical Imaging Studies
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Another prominent representative example for N-methylated PET tracer is [11C]PiB (Figure 16.10) (Klunk et al. 2004). This established diagnostic agent for imaging Aβ amyloid plaques in Alzheimer’s disease has been developed starting from fluorescent markers. However, these original compounds cannot penetrate the blood–brain barrier due to their molecular weight (Congo red) and/or salt character (Congo red, thioflavin-T). Preclinical screening of a number of radiolabeled thioflavin derivatives eventually identified [11C]PiB as a lead candidate, which has now well progressed into clinical trials and also inspired research in alternative amyloid binders (Klunk and Mathis 2008; Cohen et al. 2012; Svedberg et al. 2012). The radiochemical synthesis of [11C]PiB is based on the 11C-methylation of the aniline group of the hydroxy-protected benzothiazole precursor. This is followed by an acidic hydrolysis of the phenol-protecting group (Figure 16.10).
Prions
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Akikazu Sakudo, Takashi Onodera
Recently, the real-time quaking-induced conversion (RT-QuIC) test [22], which is a modified version of PMCA, has been developed. This method is based on the prion-seeded fibrillization of recombinant PrP. In RT-QuIC reactions, prion-associated seeds induce the amyloid fibril formation of bacterially expressed recombinant PrP in multiwell plates. The resulting amyloid fibrils are then detected by the enhanced fluorescence of an amyloid sensitive dye, thioflavin T, present in the reaction mix. RT-QuIC is known to be highly specific and sensitive for the detection of multiple human and animal prion diseases [23]. Epidemiological surveillance of CJD, which currently relies heavily on autopsy-based diagnosis, could be more efficient, cost-effective, and broadly applicable with RT-QuIC testing for cerebrospinal fluid (CSF) samples that can be obtained without autopsies [24]. The second-generation RT-QuIC assay markedly improves the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients [24].
Phenolic composition, antioxidant activity, anticholinesterase potential and modulatory effects of aqueous extracts of some seaweeds on β-amyloid aggregation and disaggregation
Published in Pharmaceutical Biology, 2019
Tosin A. Olasehinde, Ademola O. Olaniran, Anthony I. Okoh
In the second phase of the experiment, continuous aggregation of Aβ1-42 was observed in the control at different time intervals. Aggregation of the protein increased with time as shown in the control. However co-treatment with the extracts after 48 h led to disaggregation of the preformed and matured fibrils. The decrease in protein aggregates observed after the treatment suggests the disaggregation of Aβ1-42 aggregates. Better disaggregation effect of Aβ1-42 aggregates was exhibited by ECK-AQ and GEL-AQ compared to URL-AQ and RED-AQ. Furthermore, thioflavin assay was used in this study to quantify the levels of amyloid fibril. Thioflavin is an important quantitative marker of β-amyloid protein. Mostly, fluorescence intensity increases rapidly when thioflavin binds to amyloid fibrils. An increase in fluorescence intensity was observed in the control. Co-treatment with the seaweed extracts caused a decrease in fluorescence intensity. The observed decrease in fluorescence intensity with increase in incubation time which was exhibited by ECK-AQ, GEL-AQ, ULT and RED-AQ suggests loss or low levels of matured amyloid fibrils. This result correlates with the decrease in protein aggregates observed in the electron micrographs. The electron micrographs revealed that the extracts disassembled preformed aggregates and/or matured amyloid fibrils after 72 h. Our findings revealed that the constituents of the extracts may contribute to the inhibition of aggregation and disaggregation of Aβ1-42 fibrils.
Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Jie Zhu, Hongyu Yang, Yao Chen, Hongzhi Lin, Qi Li, Jun Mo, Yaoyao Bian, Yuqiong Pei, Haopeng Sun
Compounds 10d, 10 g, and 10j that showed potent ChEs inhibition activity were selected for further evaluation for their inhibitory capacity on self-induced Aβ1–42 aggregation. A thioflavin T-based fluorometric assay was performed34. Results are summarised in Table 2. Three compounds displayed significant inhibition on the aggregation of Aβ1–42 with the inhibitory rate 66.84, 65.49, and 49.51%, respectively compared to 45.72% with resveratrol as reference standard under the concentration of 25 μM. These results suggested that our compounds were MTDLs. Because of these promising in vitro data, the in vivo activities of compounds 10d and 10g were further tested.
Neuroprotective effects of a biodegradable poly(lactic-co-glycolic acid)-ginsenoside Rg3 nanoformulation: a potential nanotherapy for Alzheimer’s disease?
Published in Journal of Drug Targeting, 2018
Ravikumar Aalinkeel, Hilliard L. Kutscher, Ajay Singh, Katherine Cwiklinski, Noor Khechen, Stanley A. Schwartz, Paras N. Prasad, Supriya D. Mahajan
PLGA NPs encapsulating ginsenoside Rg3 were successfully made using an oil–water emulsion process. Angiopep-2 provides a non-invasive and flexible platform for transporting drugs or biologically active molecules into the CNS [29–31], and was incorporated into the NP surface to enable the NP to cross the BBB as well as homing on to the glial cells which also express Angiopep-2 receptors. PLGA NPs carry a negative zeta potential and adsorb the Angiopep-2 targeting peptide on to their surface. Thioflavin-T by virtue of its ability to bind amyloid protein, detects Aβ plaques that accumulate in patients with AD. ThT forms highly fluorescent complexes with amyloid fibrils and amyloid plaques. The amyloid fibrils are formed from layers of laminated β-sheets, and the Thioflavin-T binds to fibril-like β-sheets [32]. ThT can fluoresce only in the bound state when it is incorporated into amyloid fibril, therefore we used ThT fluorescence to quantitate amyloid plaques. ThT was encapsulated into the PLGA core, allows targeting amyloid fibrils. ThT exhibits bright fluorescence that can be visualised and/or fluorometrically quantified thereby providing the diagnostic component of our theranostic. We also incorporated a lipophilic dye Rhodamine 123 into our PLGA core that allowed us to track the nanoparticles (Figure 1(A)). Both the controlled release of encapsulated materials and their entrapment efficiency can be modified by changing the molecular weight, lactide:glycolide ratio and terminal chemistry of PLGA. The percentage loading efficiency can be quantitated by determining the amount of Rg3 present in the nanosuspension by high-performance liquid chromatography (HPLC), based on the initial amount of Rg3 added into the nanoemulsion, which is a fixed quantity. Based on our previous experience with PLGA nanoformulation, we are able to get a loading efficiency of about 65–70% [33,34].