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Biochemia Medica Jun 2022The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic...
INTRODUCTION
The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved.
MATERIALS AND METHODS
Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
RESULTS
All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission.
CONCLUSIONS
Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission.
Topics: Child; Child, Preschool; Cholesterol, HDL; Desmosterol; Humans; Lipoproteins; Nephrotic Syndrome; Tandem Mass Spectrometry
PubMed: 35799985
DOI: 10.11613/BM.2022.020706 -
Food & Function Nov 2021In this study, we used large, rigid, and hydrophilic zein-propylene glycol alginate composite particles (ZPCPs) and small, soft, and hydrophobic whey protein microgel...
In this study, we used large, rigid, and hydrophilic zein-propylene glycol alginate composite particles (ZPCPs) and small, soft, and hydrophobic whey protein microgel (WPM) particles to synergistically stabilize a Pickering emulsion for delivery of β-carotene. The photothermal stability and storage stability of β-carotene were improved with the combined use of different particles. Microstructural observations showed that ZPCPs were effectively adsorbed at the oil/water interface despite the substantial interparticle gaps. WPM particles could swell and stretch on the interface due to their deformable structure, thereby forming an interfacial layer of flattened particles to cover a large surface area. The interfacial structure and macroscopic properties of Pickering emulsions were modulated by adjusting the mass ratio and addition sequence of different particles. The combination of ZPCPs and WPM delayed the lipolysis during gastrointestinal digestion. Through controlling the composition of the complex interface, the free fatty acid (FFA) release rate of Pickering emulsions in the small intestinal phase was reduced from 15.64% to 9.03%. When ZPCPs were used as the inner layer and WPM as the outer layer and the mass ratio of ZPCPs to WPM was 4 : 1, the Pickering emulsion showed the best stability and β-carotene bioaccessibility. The Pickering emulsion with particle-particle complex interfaces could be applied in foods and pharmaceuticals for the purpose of enhanced stability, delayed lipolysis or sustained nutrient release.
Topics: Alginates; Biological Availability; Cryoelectron Microscopy; Drug Stability; Emulsions; Hot Temperature; Humans; Hydrogen-Ion Concentration; Lipids; Microscopy, Electron, Scanning; Osmolar Concentration; Ultraviolet Rays; Whey Proteins; Zein; beta Carotene
PubMed: 34617943
DOI: 10.1039/d1fo01714d -
The Quarterly Journal of Nuclear... Dec 2004An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides... (Review)
Review
An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.
Topics: Actinium; Alpha Particles; Antibodies, Monoclonal; Astatine; Bismuth; Humans; Isotopes; Neoplasms; Practice Patterns, Physicians'; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640792
DOI: No ID Found -
Materials (Basel, Switzerland) Dec 2022We propose a novel process to efficiently prepare highly dispersed and stable Tricalcium Phosphate (β-TCP) suspensions. TCP is coupled with a polymer to enhance its...
We propose a novel process to efficiently prepare highly dispersed and stable Tricalcium Phosphate (β-TCP) suspensions. TCP is coupled with a polymer to enhance its brittleness to be used as an artificial hard tissue. A high solid fraction of β-TCP is mixed with the polymer in order to improve the mechanical strength of the prepared material. The high solid fractions led to fast particle aggregation due to Van der Waals forces, and sediments appeared quickly in the suspension. As a result, we used a dispersant, dispex AA4040 (A40), to boost the surface potential and steric hindrance of particles to make a stable suspension. However, the particle size of β-TCP is too large to form a suspension, as the gravity effect is much more dominant than Brownian motion. Hence, β-TCP was subjected to wet ball milling to break the aggregated particles, and particle size was reduced to ~300 nm. Further, to decrease sedimentation velocity, cellulose nanocrystals (CNCs) are added as a thickening agent to increase the overall viscosity of suspension. Besides the viscosity enhancement, CNCs were also wrapped with A40 micelles and increase the stability of the suspension. These CNC/A40 micelles further facilitated stable suspension of β-TCP particles with an average hydration radius of 244.5 nm. Finally, β-TCP bone cement was formulated with the suspension, and the related cytotoxicity was estimated to demonstrate its applicability for hard tissue applications.
PubMed: 36614568
DOI: 10.3390/ma16010228 -
International Journal of Molecular... Aug 2022Glycogen is an easily accessible source of energy for various processes. In hepatocytes, it can be found in the form of individual molecules (β-particles) and their...
Glycogen is an easily accessible source of energy for various processes. In hepatocytes, it can be found in the form of individual molecules (β-particles) and their agglomerates (α-particles). The glycogen content in hepatocytes depends on the physiological state and can vary due to the size and number of the particles. Using biochemical, cytofluorometric, interferometric and morphometric methods, the number of β-particles in rat hepatocytes was determined after 48 h of fasting at different time intervals after glucose refeeding. It has been shown that after starvation, hepatocytes contain ~1.6 × 10 β-particles. During refeeding, their number of hepatocytes gradually increases and reaches a maximum (~5.9 × 10) at 45 min after glucose administration, but then quickly decreases. The data obtained suggest that in cells there is a continuous synthesis and degradation of particles, and at different stages of life, one or another process predominates. It has been suggested that in the course of glycogenesis, pre-existing β-particles are replaced by those formed de novo. The main contribution to the deposition of glycogen is made by an increase in the glucose residue number in its molecules. The average diameter of β-particles of glycogen during glycogenesis increases from ~11 nm to 21 nm.
Topics: Animals; Fasting; Glucose; Glycogen; Hepatocytes; Liver; Rats; Starvation
PubMed: 36012534
DOI: 10.3390/ijms23169263 -
Molecules (Basel, Switzerland) Aug 2022Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been... (Review)
Review
Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RP) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.
Topics: Beta Particles; Diagnostic Imaging; Humans; Neoplasms; Radioisotopes; Radiopharmaceuticals
PubMed: 36014472
DOI: 10.3390/molecules27165231 -
Journal of Nuclear Medicine : Official... Apr 2023Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in...
Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in treatment for metastatic and locoregional disease. Peptide receptor radionuclide therapy with Lu-DOTATATE (DOTA-octreotate), a β-particle-emitting somatostatin derivative, has demonstrated survival benefit in patients with SSTR-positive NETs. Despite excellent results, a subset of patients has tumors that are resistant to treatment, and alternative agents are needed. Targeted α-particle therapy has been shown to kill tumors that are resistant to targeted β-particle therapy, suggesting that targeted α-particle therapy may offer a promising treatment option for patients with Lu-DOTATATE-resistant disease. Although DOTATATE can chelate the clinically relevant α-particle-emitting radionuclide Ac, the labeling reaction requires high temperatures, and the resulting radioconjugate has suboptimal stability. We designed and synthesized MACROPATATE (MACROPA-octreotate), a novel radioconjugate capable of chelating Ac at room temperature, and assessed its in vitro and in vivo performance. MACROPATATE demonstrated comparable affinity to DOTATATE (dissociation constant, 21 nM) in U2-OS-SSTR2, a SSTR2-positive transfected cell line. Ac-MACROPATATE demonstrated superior serum stability at 37°C over time compared with Ac-DOTATATE. Biodistribution studies demonstrated higher tumor uptake of Ac-MACROPATATE than of Ac-DOTATATE in mice engrafted with subcutaneous H69 NETs. Therapy studies showed that Ac-MACROPATATE exhibits significant antitumor and survival benefit compared with saline control in mice engrafted with SSTR-positive tumors. However, the increased accumulation of Ac-MACROPATATE in liver and kidneys and subsequent toxicity to these organs decreased its therapeutic index compared with Ac-DOTATATE. Ac-MACROPATATE and Ac-DOTATATE exhibit favorable therapeutic efficacy in animal models. Because of elevated liver and kidney accumulation and lower administered activity for dose-limiting toxicity of Ac-MACROPATATE, Ac-DOTATATE was deemed the superior agent for targeted α-particle peptide receptor radionuclide therapy.
Topics: Mice; Animals; Octreotide; Neuroendocrine Tumors; Organometallic Compounds; Tissue Distribution; Somatostatin; Receptors, Somatostatin; Radioisotopes; Radiopharmaceuticals
PubMed: 36396453
DOI: 10.2967/jnumed.122.264707 -
Journal of Nuclear Medicine : Official... Sep 2017In recent years, new α-particle-, β-particle-, and Auger electron-emitting radiometals-such as Cu, Sc, Ho, Tb, Tb, Pb/Bi, Ac, and Bi-have been produced and evaluated... (Review)
Review
In recent years, new α-particle-, β-particle-, and Auger electron-emitting radiometals-such as Cu, Sc, Ho, Tb, Tb, Pb/Bi, Ac, and Bi-have been produced and evaluated (pre)clinically for therapeutic purposes. In this short review article, the most important routes of production of these radiometals are critically discussed, as are examples of their application in preclinical and clinical studies.
Topics: Alpha Particles; Animals; Beta Particles; Electrons; Humans; Metals; Radiochemistry; Radioisotopes
PubMed: 28864619
DOI: 10.2967/jnumed.116.186825 -
Scientific Reports Jul 2019A novel omics-like method referred to as "particle morphomics" has been proposed in the present study. The dynamic images of >2,000,000 particles per sample in...
A novel omics-like method referred to as "particle morphomics" has been proposed in the present study. The dynamic images of >2,000,000 particles per sample in sediments, soils and dusts were collected by a Sympatec GmbH QICPIC particle size and shape analyzer, and the morphological descriptors of each particle including equivalent diameter, sphericity, aspect ratio and convexity were extracted as the "particle morphome". Various multivariate analyses were adopted to process the high-throughput data of particle morphome including analyses of alpha and beta diversities, similarity, correlation, network, redundancy, discretion and principal coordinate. The outcome of particle morphomics could estimate the morphological diversity and sketch the profile of morphological structure, which aided to develop a morphological fingerprint for specific particle samples. The distribution and properties of particle assemblages of specific morphology could also be evaluated by selecting particles with respect to filter criteria. More importantly, the particle morphomics may be extended to investigate and explain the biogeochemical and environmental processes involved with particle morphology if linked with external variables.
PubMed: 31270428
DOI: 10.1038/s41598-019-46062-6 -
Acta Biochimica Polonica 2011The pre-β HDL fraction constitutes a heterogeneous population of discoid nascent HDL particles. They transport from 1 to 25 % of total human plasma apo A-I. Pre-β HDL... (Review)
Review
The pre-β HDL fraction constitutes a heterogeneous population of discoid nascent HDL particles. They transport from 1 to 25 % of total human plasma apo A-I. Pre-β HDL particles are generated de novo by interaction between ABCA1 transporters and monomolecular lipid-free apo A-I. Most probably, the binding of apo A-I to ABCA1 initiates the generation of the phospholipid-apo A-I complex which induces free cholesterol efflux. The lipid-poor nascent pre-β HDL particle associates with more lipids through exposure to the ABCG1 transporter and apo M. The maturation of pre-β HDL into the spherical α-HDL containing apo A-I is mediated by LCAT, which esterifies free cholesterol and thereby forms a hydrophobic core of the lipoprotein particle. LCAT is also a key factor in promoting the formation of the HDL particle containing apo A-I and apo A-II by fusion of the spherical α-HDL containing apo A-I and the nascent discoid HDL containing apo A-II. The plasma remodelling of mature HDL particles by lipid transfer proteins and hepatic lipase causes the dissociation of lipid-free/lipid-poor apo A-I, which can either interact with ABCA1 transporters and be incorporated back into pre-existing HDL particles, or eventually be catabolized in the kidney. The formation of pre-β HDL and the cycling of apo A-I between the pre-β and α-HDL particles are thought to be crucial mechanisms of reverse cholesterol transport and the expression of ABCA1 in macrophages may play a main role in the protection against atherosclerosis.
Topics: ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Animals; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins; Apolipoproteins M; Cholesterol; High-Density Lipoproteins, Pre-beta; Humans; Lipase; Lipocalins; Phosphatidylcholine-Sterol O-Acyltransferase
PubMed: 21750785
DOI: No ID Found