Relevant bibliographies by topics / Medical Biochemistry: Lipids

Academic literature on the topic 'Medical Biochemistry: Lipids'

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Published: 4 June 2021
Last updated: 29 January 2023

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Journal articles on the topic "Medical Biochemistry: Lipids"

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Honek, John F. "Glyoxalase biochemistry." Biomolecular Concepts 6, no. 5-6 (December 1, 2015): 401–14. http://dx.doi.org/10.1515/bmc-2015-0025.

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AbstractThe glyoxalase enzyme system utilizes intracellular thiols such as glutathione to convert α-ketoaldehydes, such as methylglyoxal, into D-hydroxyacids. This overview discusses several main aspects of the glyoxalase system and its likely function in the cell. The control of methylglyoxal levels in the cell is an important biochemical imperative and high levels have been associated with major medical symptoms that relate to this metabolite’s capability to covalently modify proteins, lipids and nucleic acid.
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Oostendorp, Marlies, Udo FH Engelke, Michèl AAP Willemsen, and Ron A. Wevers. "Diagnosing Inborn Errors of Lipid Metabolism with Proton Nuclear Magnetic Resonance Spectroscopy." Clinical Chemistry 52, no. 7 (July 1, 2006): 1395–405. http://dx.doi.org/10.1373/clinchem.2006.069112.

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Abstract Background: Many severe diseases are caused by defects in lipid metabolism. As a result, patients often accumulate unusual lipids in their blood and tissues, and proper identification of these lipids is essential for correct diagnosis. In this study, we investigated the potential use of proton nuclear magnetic resonance (1H-NMR) spectroscopy to simultaneously identify and quantify (un)usual lipids present in the blood of patients with different inborn errors of lipid metabolism. Methods: We extracted blood plasma or serum lipids in chloroform–methanol (2:1 by volume). After addition of the nonvolatile chemical shift and concentration reference compound octamethylcyclotetrasiloxane, we performed 1H-NMR measurements on a 500-MHz spectrometer. Assignments were based on the literature, computer simulations, and reference spectra of relevant authentic standards. Results: Spectra of normal plasma samples allowed the identification of 9 lipid species. We found good correlation between conventional methods and 1H-NMR for cholesterol and triglyceride concentrations. We also investigated 4 inborn errors of lipid metabolism (3 in sterol metabolism and 1 in fatty acid metabolism). NMR analysis led to a correct diagnosis for all 4 diseases, whereas the concentration of the diagnostic metabolite could be determined for 3. Conclusions: 1H-NMR spectroscopy of blood plasma or serum lipid extracts can be used to accurately identify and quantify lipids. The method can also identify unusual lipids in the blood of patients with inborn errors of lipid metabolism. This technique may therefore be applicable in clinical diagnosis and follow-up.
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AHSAN, HASEEB. "Clinical Chemistry and Biochemistry: The Role of Biomarkers and Biomolecules." Asian Journal of Science Education 4, no. 1 (April 22, 2022): 17–24. http://dx.doi.org/10.24815/ajse.v4i1.24431.

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Biochemistry is a branch of biosciences which deals with the study of chemical reactions that occur in living cells and organisms. It is a subject in which biological phenomenon is analyzed in terms of chemical reactions or metabolic pathways. Biochemistry has been previously named as biological chemistry, chemical biology, clinical chemistry, chemical pathology, physiological chemistry, including medical biochemistry and clinical biochemistry. Medical biochemistry studies the chemical composition and physiological reactions in the human body. Clinical biochemistry is the measurement of chemicals or analytes in body fluids for the diagnosis, monitoring and management of patients with various diseases such as diabetes, cardiovascular diseases, etc. An increase in the number and availability of laboratory diagnostics has helped in the solution of clinical problems. Particularly important is the contribution of clinical chemistry to the diagnosis and monitoring of diabetes. The importance of lipids and lipoproteins for public health has increased with clinical studies showing the benefit of lipid lowering in cardiovascular diseases. An understanding of clinical chemistry and biochemistry would be useful in the study of medical and allied sciences for the advancement of knowledge in academic and professional courses. This review article is an attempt to understand the scope and significance of basic and applied aspects of biochemistry
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Wild, R. A., D. Applebaum-Bowden, L. M. Demers, M. Bartholomew, J. R. Landis, W. R. Hazzard, and R. J. Santen. "Lipoprotein lipids in women with androgen excess: independent associations with increased insulin and androgen." Clinical Chemistry 36, no. 2 (February 1, 1990): 283–89. http://dx.doi.org/10.1093/clinchem/36.2.283.

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Abstract Concentrations of triglycerides are increased and concentrations of high-density lipoprotein (HDL) cholesterol are low in women with hyperandrogenism. These alterations could be related to excessive androgen or estrogen, to hyperinsulinism, or to a combination of these abnormalities. We examined their independent influences on lipids in 21 women with hyperandrogenism, subgrouped according to apparent source of androgen excess. Results for lipid, androgen, and insulin did not differ among subgroups, so these data were pooled. Free plus albumin-bound testosterone (uT) was correlated with triglycerides (r = 0.69, P less than 0.01) and HDL cholesterol (r = -0.56, P less than 0.01). Both triglycerides (r = 0.66, P less than 0.01) and HDL cholesterol (r = -0.48, P less than 0.05) were also correlated with insulin measured during fasting. Partial correlation revealed that, after adjusting for insulin, lipids were associated with uT. This suggests that androgen excess is independently related to lipid excess. Insulin also was correlated with lipids when adjusted for uT. Free plus albumin-bound estradiol was not associated with any of the lipids. We conclude that altered lipids in women with hyperandrogenism result from the independent effects of androgen and insulin.
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Jordan, P., D. Brubacher, U. Moser, H. B. Stähelin, and K. F. Gey. "Vitamin E and vitamin A concentrations in plasma adjusted for cholesterol and triglycerides by multiple regression." Clinical Chemistry 41, no. 6 (June 1, 1995): 924–27. http://dx.doi.org/10.1093/clinchem/41.6.924.

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Abstract The plasma concentration of vitamins A and E varies with the amount of concurrent lipids and thus requires lipid standardization. The present study compares a new multiple regression-based method for adjusting vitamins A and E concentrations for cholesterol and triglycerides with previous methods (adjustment for cholesterol only, and adjustment for the sum of cholesterol and triglycerides). The results show that the new method can reduce influence of the concurrent lipids.
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Bel’Skaya, L. V., E. A. Sarf, and D. V. Solomatin. "DETERMINATION OF THE QUANTITATIVE CONTENT OF LIPIDS IN A BIOLOGICAL MATERIAL BY THE METHOD OF IR SPECTROSCOPY." Russian Clinical Laboratory Diagnostics 64, no. 4 (October 7, 2019): 204–9. http://dx.doi.org/10.18821/0869-2084-2019-64-4-204-209.

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A modification of the Folch method has been proposed for the quantitative determination of lipids in biological material, in which, after extraction of lipids with a chloroform / ethanol mixture, lipids are determined using IR spectroscopy. The bands corresponding to the stretching and deformation vibrations of the methyl and methylene groups of lipids and fatty acids were selected as analytical absorption bands: 1396, 1458, 2853, and 2923 cm- 1. These bands do not intersect with the absorption bands of proteins and nucleic acids, thus avoiding the stage of preliminary cleaning of lipids from non-lipid impurities. A multifactor regression model was constructed, which allows experimental data to be described with an error not exceeding 12%.
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Franck, P., J. L. Sallerin, H. Schroeder, M. A. Gelot, and P. Nabet. "Rapid determination of fecal fat by Fourier transform infrared analysis (FTIR) with partial least-squares regression and an attenuated total reflectance accessory." Clinical Chemistry 42, no. 12 (December 1, 1996): 2015–20. http://dx.doi.org/10.1093/clinchem/42.12.2015.

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Abstract Fecal lipid content is usually determined by titrimetric or gravimetric methods, but these methods are time consuming and involve dangerous solvents. We have developed a new method of measuring fecal lipids by Fourier transform infrared spectrometry (FTIR) with an attenuated total reflectance accessory that is fast and requires no solvents. The spectra of stools from 4000 to 750 cm-1 were analyzed, and the lipid concentrations were measured by using a calibration curve prepared by partial least-squares analysis of data from 34 stools. The linearity of the method was tested by mixing low-lipid stools with lipid-overloaded stools to give a range of 0.5-15% lipid. The prediction residual values were -0.49-0.78% for calibrators, and -2.55-2.34% for unknown samples. There was good agreement between the fecal lipids measured by gravimetric (x) and FTIR(y) methods: y = 0.87x + 5.5. The standard error of prediction was 1.07%.
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Guille, Jennifer, John K. Raison, and Janusz M. Gebicki. "Radiation-induced lipid peroxidation and the fluidity of erythrocyte membrane lipids." Free Radical Biology and Medicine 3, no. 2 (January 1987): 147–52. http://dx.doi.org/10.1016/s0891-5849(87)80010-2.

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Wratten, M. L., A. A. van't Veld, U. A. van der Heide, G. van Ginkel, A. Sevanian, and Y. K. Levine. "Structural and dynamic effects of oxidized lipids in unsaturated lipid membranes." Free Radical Biology and Medicine 9 (January 1990): 124. http://dx.doi.org/10.1016/0891-5849(90)90618-s.

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Friedlander, Y., J. D. Kark, and Y. Stein. "Variability of plasma lipids and lipoproteins: the Jerusalem Lipid Research Clinic Study." Clinical Chemistry 31, no. 7 (July 1, 1985): 1121–26. http://dx.doi.org/10.1093/clinchem/31.7.1121.

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Abstract We examined the variability of lipid and lipoprotein concentrations in plasma from a population sample from the Jerusalem Lipid Research Clinic study. Coefficients of variation of about 8% for plasma cholesterol, 11% to 15% for low- and high-density-lipoprotein cholesterol, and about 30% for triglyceride were reported, both for 17-year-olds and adults examined twice, with a median period of two months between measurements. Stability was similar in a subsample of adults who had an additional measurement a median of 28 months later. Within-assay analytical variation (CV) was 1.9-2.0% for cholesterol, 1.5-2.3% for triglyceride, and 4.5% for high-density-lipoprotein cholesterol. Between-assay variation was 3-5% for cholesterol and triglyceride and 10% for high-density-lipoprotein cholesterol. The lower stability of the lipoprotein fractions of cholesterol than of total cholesterol emphasizes the need for repeated measurements of these fractions for more accurate characterization of subjects, especially those with extreme values, both for clinical use and for predicting outcome in follow-up studies.
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Dissertations / Theses on the topic "Medical Biochemistry: Lipids"

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Jonnalagadda, Deepa. "HETEROGENEITY IN PLATELET EXOCYTOSIS." UKnowledge, 2013. http://uknowledge.uky.edu/biochem_etds/8.

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Platelet exocytosis is essential for hemostasis and for many of its sequelae. Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically-controlled process? My work describes platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (i.e. thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed and extent of release. PAR4-agonist induced slower release of fewer molecules while thrombin rapidly induced the greatest release. Cargo with opposing actions (e.g. pro- and anti-angiogenic) had similar release profiles, suggesting limited thematic response to specific agonists. From the release time-course data, rate constants were calculated and used to probe for underlying patterns. Probability density function and operator variance analyses were consistent with three classes of release events, differing in their rates. The distribution of cargo into these three classes was heterogeneous suggesting that platelet secretion is a stochastic process potentially controlled by several factors such as cargo solubility, granule shape, and/or granule-plasma membrane fusion routes. Sphingosine 1 phosphate (S1P) is a bioactive lipid that is stored in platelets. S1P is essential for embryonic development, vascular integrity, and inflammation. Platelets are an abundant source of S1P due to the absence of the enzymes that degrade it. Platelets release S1P upon stimulation. My work attempts to determine how this bioactive lipid is released from platelets. Washed platelets were stimulated with agonists for defined periods of time and the supernatant and pellet fractions were separated by centrifugation. Lipids were separated by liquid phase extraction and S1P was quantified with a triple quadrapole mass spectrometer. A carrier molecule (BSA) is required to detect release of S1P. Further, there is a dose-dependent increase in total S1P with increasing BSA. S1P release shows characteristics similar to other platelet granule cargo e.g. platelet factor IV (PF4). Platelets from Unc13-d Jinx mice and VAMP8-/- mice, which are secretion-deficient (dense granule, alpha granule and lysosome), were utilized to understand the process of S1P release. S1P release was more affected in Unc13-d Jinx mice mirroring their dense granule secretion defect. Fluorescence microscopy and sub-cellular fractionation were used to examine localization of S1P in platelets. S1P was observed to be enriched in a granule population. These studies indicate the existence of two pools of S1P, a readily extractable agranular pool, sensitive to BSA, and a granular pool that requires the secretion machinery for release. The secretion machinery of platelets in addition to being involved in the release of normal granule cargo is thus proved to be involved in the release of bioactive lipid molecules like S1P.
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Haraszti, Reka A. "Engineered Exosomes for Delivery of Therapeutic siRNAs to Neurons." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/971.

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Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data. We established that cholesterol-conjugated siRNAs passively associate to EV membrane and can be productively delivered to target neurons. We extensively characterized this loading process and optimized exosome-to-siRNA ratios for loading. We found that chemical stabilization of 5'-phosphate with 5'-E-vinylphosphonate and chemical stabilization of all nucleotides with 2'-O-methyl and 2'-fluoro increases the accumulation of siRNA and the level of mRNA silencing in target cells. Therefore, we recommend using fully modified siRNAs for lipid-mediated loading to EVs. Later, we identified that α-tocopherol-succinate (vitamin E) conjugation to siRNA increases productive loading to exosomes compared to originally described cholesterol. Low EV yield has been a rate-limiting factor in preclinical development of the EV technology. We developed a scalable EV manufacturing process based on three-dimensional, xenofree culture of mesenchymal stem cells and concentration of EVs from conditioned media using tangential flow filtration. This process yields exosomes more efficient at siRNA delivery than exosomes isolated via differential ultracentrifugation from two-dimensional cultures of the same cells. In-depth characterization of EV content is required for quality control of EV preparations as well as understanding composition–activity relationship of EVs. We have generated mass-spectrometry data on more than 3000 proteins and more than 2000 lipid species detected in exosomes (small EVs) and microvesicles (large EVs) isolated from five different producer cells: two cell lines (U87 and Huh7) and three mesenchymal stem cell types (derived from bone marrow, adipose tissue and umbilical cord Wharton’s jelly). These data represent an indispensable resource for the community. Furthermore, relating composition change to activity change of EVs isolated from cells upon serum deprivation allowed us to identify essential components of siRNA-delivering exosomes. Based on these data we reverse engineered natural exosomes into artificial exosomes consisting of dioleoyl-phosphatidylcholine, cholesterol, dilysocardiolipin, Rab7, AHSG and Desmoplakin. These artificial exosomes reproduced efficient siRNA delivery of natural exosomes both in vitro and in vivo. Artificial exosomes may facilitate manufacturing, quality control and cargo loading challenge that currently impede the therapeutic EV field.
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Kénanian, Gérald. "Staphylococcus aureus se met transitoirement en dormance pour utiliser les acides gras de l'hôte et échapper à une inhibition par un anti-FASII : quel signal active son réveil ?" Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS242.

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Le traitement des infections dues aux bactéries multirésistantes aux antibiotiques est un défi médical majeur du 21ème siècle. Ce défi a incité la recherche de cibles ayant des fonctions essentielles pour le développement de nouveaux antibiotiques. Les enzymes de la voie FASII, responsables de la synthèse des acides gras (AG), sont considérées comme essentielles et de nombreux antibiotiques, appelés anti-FASII, ont été développés pour lutter contre des pathogènes du phylum des Firmicutes. Cependant, notre laboratoire a montré que plusieurs pathogènes contournent l’inhibition des anti-FASII par l’utilisation des AGs exogènes abondants chez l’hôte (sang, organes, aliments). Ce contournement compromet l’utilisation des anti-FASII en traitement. Le statut du pathogène majeur, Staphylococcus aureus, est néanmoins resté en débat. Il synthétise un AG non disponible chez l’hôte, et donc, d’après la littérature, ne pourrait pas être compensé. La question de cette thèse est de comprendre les mécanismes utilisés par S. aureus lui permettant de contourner les anti-FASII. Deux mécanismes sont mis en évidence: I- Des mutations à haute fréquence du gène fabD surviennent et permettent à la bactérie d’utiliser des AGs exogènes. Ce type de mutation favorise la disponibilité de la protéine ACP permettant l’utilisation des AGs exogènes. II- Une stratégie sans mutation décelable survient en présence de fluides hôtes tels que le sérum. Elle comprend une première étape de "dormance" d’environ 8 à 10 heures pendant laquelle des AGs sont incorporés. Durant cette adaptation les bactéries semblent bloquées dans la division cellulaire, et subissent des changements morphologiques. Cette étape est suivie par une reprise de croissance « normale » où S. aureus utilise librement des AGs exogènes et reste insensible aux anti-FASII. Dans nos conditions, une étude microscopique « time-lapse », a permis de visualiser qu’environ 3% de la population bactérienne adaptée aux anti-FASII émerge. Nos résultats pointent vers un mécanisme d’adaptation dans lequel le sérum diminuerait le stress bactérien et augmenterait ainsi la disponibilité de l’ACP et des AGs exogènes, facilitant leur utilisation pour la synthèse des phospholipides. Les AGs exogènes peuvent donc remplacer totalement les endogènes. Ce résultat va à l’encontre de l’hypothèse couramment acceptée qu’un AG endogène de S. aureus est conservé et essentiel. Nous avons poursuivi cette étude par des analyses protéomiques et par le criblage d’une banque de 2000 mutants de S. aureus en cherchant des loci impliqués dans l’adaptation aux anti-FASII. Des fonctions de la réponse au stress, la division cellulaire et le métabolisme des lipides semblent être impliqués dans cette adaptation. Pour conclure, cette étude a permis de clarifier les étapes impliquées dans la réponse adaptative de S. aureus aux anti-FASII. Même si nos résultats prouvent que S. aureus contourne les anti-FASII, une approche combinatoire pourrait être envisagée où l’anti-FASII serait couplé avec un deuxième inhibiteur qui bloquerait sa capacité à sortir de la dormance
Treatment of infections caused by multidrug-resistant bacteria is a major medical challenge of the 21st century, which has stimulated the search for essential bacterial functions as potential antimicrobial drug targets. The fatty acid synthesis (FASII) pathway enzymes are considered essential, and numerous antibiotics called (anti-FASII), have been developed to eliminate pathogens of the Firmicutes phylum. However, our laboratory has shown that several pathogens bypass FASII inhibitors by incorporating exogenous fatty acids (FAs), which are abundant in the host (in blood, organs and foods). FASII bypass thus compromises the use of FASII-based antibiotics. The status of the major pathogen, Staphylococcus aureus, has remained in debate. S. aureus synthesizes an FA not produced by the host and according to the literature, is required and would not be available in the host. However, work in my lab showed that indeed bypasses FASII. The goal of my research project is to understand the mechanisms used by S. aureus to bypass FASII antibiotics. Two mechanisms are highlighted: I- High frequency mutations of the fabD gene allow S. aureus to use exogenous FAs; our study indicates that higher availability of ACP in these mutants facilitates FA utilization. II- A strategy without detectable mutation occurs in the presence of host fluids such as serum. It comprises a first "dormancy" step of about 8 to 10 hours, followed by outgrowth; FAs are incorporated throughout these steps. The latency phase appears to be due to a division block, during which cells undergo morphological changes. During "normal" growth recovery, S. aureus freely uses exogenous FAs and remains insensitive to anti-FASII. Using « time-lapse » microscopic study, we showed in our test conditions that about 3% of the bacterial population adapted to FASII antibiotics. Ours results point to an adaptation mechanism in which serum decreases bacterial stress, leading to increased availability of ACP and exogenous FAs. These substrates can then be used for phospholipid synthesis. These results resolve the debate by showing that S. aureus can replace endogenous FAs with exogenous FAs when FASII is blocked. Contrary to current dogma, FASII is not essential in S. aureus. To identify the loci involved in adaptation to anti-FASII, we performed proteomic analyses and also screened a S. aureus mutant library. Functions of stress response, cell division, and lipid metabolism appear to be involved in this adaptation. To conclude, this study clarified the steps leading to S. aureus adaptation to FASII antibiotics. Although our results show that S. aureus bypasses anti-FASII, a combinatorial approach could be considered in which FASII antibiotics could be coupled to a second inhibitor that would prevent exit from the dormancy
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(7041221), Shayak Samaddar. "Delivery Strategies for Nucleic Acids." Thesis, 2019.

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Utilization of nucleic acids to manipulate genetic information within a cell is known as gene therapy. It has provided researchers with unprecedented opportunities in treatment and mitigation of several life-threatening diseases. Gene therapy is an attractive alternative to conventional chemotherapy or radiation therapy due to its high efficiency, minimal side effects, and potential to evade drug resistance. The versatility of gene therapy makes it useful for the treatment of diseases dangerous disease like cancer. However, delivery of nucleic acid payloads to the intended target has been the bottleneck in clinical translation of such therapies. Here, we have developed and evaluated three different delivery systems (lipid based, polymer based and lipid-polymer hybrid) which can complex nucleic acid payloads, able to target specific cell types and get dissembled on cellular internalization to release the therapeutic payload. Our lipid and lipid-polymer hybrid delivery systems utilize a novel bacterial peptide sequence which enables these vectors to “stick” to fibronectin present in tumor extracellular matrix making them attractive for intravesical administration in bladder cancer management. Additionally, these systems have pH responsive modalities which aids in vector dissemble under acidic endosomal pH conditions for efficient release of therapeutic cargos after internalization into target cells.

In our efforts to develop an ideal delivery system with a tunable the assembly/disassembly properties, we synthesized a library of pendent polymer with biodegradable polycarbonate backbone. The ability of the pendent groups to form host-gest interaction with hydrophobic core of cationic cyclodextrins determined the stability of the delivery system. We demonstrate the capability of such polymer systems to form nano-dimensinal complexes with nucleic acid and transfect cancer cells. The above-mentioned property of cyclodextrins to form host-guest interaction with hydrophobic molecules also forms the basis of its utilization in the treatment of a rare metabolic disorder called Niemann Pick type C disease where there the cells loses the ability to remove stored cholesterol from endo-lysosomal compartments. Cyclodextrin forms host-gest complexes with aberrantly stored cholesterol and helps normalization of cellular cholesterol level. However, the soluble nature and small size of the cyclodextrin causes very rapid clearance for the body necessitating dosage levels as high as 9000mg/kg for therapeutic benefit. We have also developed a library of polyrotaxanes, where multiple cyclodextrins are threaded onto linear polymer chains and end-capped with bulky groups to prevent slippage. This kind to assembly drastically increases the systemic circulation time by preventing rapid renal clearance. We evaluated the ability of these constructs to serve as a long circulation delivery system for delivery of β-cyclodextrins for potential treatment of Niemann Pick type C disease. Finally, we have studied the structure-function relationships of these supramolecular assemblies to aid in rational design of therapeutic polyrotaxanes.
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(8933363), Ahmad Abdurahman M. Alhulail. "FAT AND SODIUM QUANTIFICATION AND CORRELATION BY MRSI." Thesis, 2020.

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Lipids and sodium (23Na) are two essential components of the human body. They play a role in almost all biological systems. However, an increase in their levels is associated with metabolic diseases. The elevation of their contents can cause similar health disorders. Examples of prevalent disorders that share an increase of musculoskeletal lipids and 23Na are hypertension and diabetes. However, the relationship between in vivo lipid and sodium levels in pathophysiology has not been studied enough and therefore is still unclear. Additionally, the available quantification methods to facilitate such a study may not be practical. They are either invasive, not sensitive enough, or require an impractical measurement time.

Therefore, in this work, our aims were to develop practical in vivo methods to quantify the absolute sodium concentration as well as the concentration of each lipid component individually, and to study the correlation between them within the skeletal muscles.

Since lipids and 23Na have different nuclear magnetic resonance properties, their quantification by magnetic resonance (MR) techniques face different challenges. Thus, we optimized different MR spectroscopic imaging (MRSI) techniques for lipids and 23Na.

Our proposed proton MRSI was able to provide eight lipid fat fraction (FF) maps representing each musculoskeletal lipid component (fatty acid) detected by our MRSI technique, and demonstrated a superior sensitivity compared to the conventional MR imaging methods.

For 23Na, our developed 23Na-MRSI was able to measure and map the absolute 23Na concentration with values agreeing with those reported previously in biopsy studies, and with a high repeatability (CV < 6 %) within significantly shorter acquisition time compared to other available techniques.

Finally, the 23Na concentration and the fat fractions of each lipid component within healthy skeletal muscles were measured and correlated using our developed MRSI methods. Our findings suggest a positive regional relationship between 23Na and lipids and negative correlation between 23Na and BMI under healthy conditions.

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Sinn, Natalie. "Omega-3 fatty acids, micronutrients and cognitive and behaviour problems associated with child attention deficit hyperactivity disorder." 2006. http://arrow.unisa.edu.au:8081/1959.8/46377.

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This thesis concerns the role of nutrients in cognitive and behaviour problems associated with child attention deficit hyperactivity disorder (ADHD). Study 1 investigated relationships between Conners' ADHD Index ratings, fatty acid deficiency symptoms (FADS), and cognitive performance in a normal population of children. Studies 2 and 3 comprised a 30 week intervention trial investigating effects of n-3 PUFA supplementation on ADHD symptoms in 7-12 year old children with high ADHD scores.
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(6597242), Clint M. Alfaro. "DEVELOPMENT OF AMBIENT IONIZATION MASS SPECTROMETRY FOR INTRAOPERATIVE CANCER DIAGNOSTICS AND SURGICAL MARGIN ASSESSMENT." Thesis, 2019.

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Advancements in cancer treatments have increased rapidly in recent years, but cures remain elusive. Surgical tumor resection is a central treatment for many solid malignancies. Residual tumor at surgical margins leads to tumor recurrence. Novel tools for assessing residual tumor at surgical margins could improve surgical outcomes by helping to maximize the extent of resection. Ambient ionization-mass spectrometry (MS) methods generate and analyze ions from minimally prepared samples in near-real-time (e.g. seconds to minutes). These methods leverage the high sensitivity and specificity of mass spectrometry for analyzing gas phase ions and generating those ions quickly and with minimal sample preparation. Recent work has shown that differential profiles of ions, corresponding to phospholipids and small metabolites, are detected from cancerous and their respective normal tissue with ambient ionization-MS methods. When properly implemented, ambient ionization-MS could be used to assess for tumor at surgical margins and provide a molecular diagnosis during surgery.

The research herein reports efforts in developing rapid intraoperative ambient ionization-MS methods for the molecular assessment of cancerous tissues. Touch spray (TS) ionization and desorption electrospray ionization (DESI) were utilized to analyze kidney cancer and brain cancer.

As a demonstration of the applicability of TS-MS to provide diagnostic information from fresh surgical tissues, TS-MS was used to rapidly analyze renal cell carcinoma and healthy renal tissue biopsies obtained from human subjects undergoing nephrectomy surgery. Differential phospholipid profiles were identified using principal component analysis (PCA), and the significant ions were characterized using multiple stages of mass spectrometry and high resolution/exact mass MS. The same TS-MS analyzed renal tissues were subsequently analyzed with DESI-MS imaging to corroborate the TS-MS results, and the significant DESI-MS ions were also characterized with MS.

Significant efforts were made in developing and evaluating a standalone intraoperative DESI-MS system for analyzing brain tissue biopsies during brain tumor surgery. The intraoperative DESI-MS system consists of a linear trap quadrupole mass spectrometer placed on a custom-machined cart that contains all hardware for operating the mass spectrometer. This instrument was operated in the neurosurgical suites at Indiana University School of Medicine to rapidly analyze brain tissue biopsies obtained from glioma resection surgeries. A DESI-MS library of normal brain tissue and glioma was used to statistically classify the brain tissue biopsies collected in the operating room. Multivariate statistical methodologies were employed to predict the disease state and tumor cell percentage of the samples. A DESI-MS assay for detecting 2-hydroxyglutarate (2HG), the oncometabolic product of the isocitrate dehydrogenase (IDH) mutation (a key glioma prognostic marker), was developed and applied to determine the IDH mutation status during the surgical resection. The strengths, weaknesses, and areas of future work in this field are discussed.

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Gulati, Sonia. "Characterizing the Interaction of the ATP Binding Cassette Transporters (G subfamily) with the Intracellular Protein Lipid Environment." Thesis, 2011. https://doi.org/10.7916/D8ZW1SW7.

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Cholesterol is an essential molecule that mediates a myriad of critical cellular processes, such as signal transduction in eukaryotes, membrane fluidity, and steroidogenesis. As such it is not surprising that cholesterol homeostasis is tightly regulated, striking a precise balance between endogenous synthesis and regulated uptake/efflux to and from extracellular acceptors. In mammalian cells, sterol efflux is a key component of the homeostatic equation and is mediated by members of the ATP binding cassette (ABC) transporter superfamily. ATP-binding cassette (ABC) transporters represent a group of evolutionarily highly conserved cellular transmembrane proteins that mediate the ATP-dependent translocation of substrates across membranes. Members of this superfamily, ABCA1 and ABCG1, are key components of the reverse cholesterol transport pathway. ABCG1 acts in concert with ABCA1 to maximize the removal of excess cholesterol from cells by promoting cholesterol efflux onto mature and nascent HDL particles, respectively. To date, mammalian ABC transporters are exclusively associated with efflux of cholesterol. In Saccharomyces cerevisiae, we have demonstrated that the opposite (i.e inward) transport of sterol in yeast is also dependent on two ABC transporters (Aus1p and Pdr11p). This prompts the question what dictates directionality of sterol transport by ABC transporters. The main focus of this study is to define the parameters that result in sterol movement across membranes. The comparison between these contrasting states (outward v. inward transport of the same substrate) will allow us to dissect whether sterol transport across the plasma membrane is defined by the molecule (i.e. the ABC transporter) or by microenvironment (i.e. the status of other proteins and lipids) in which it resides. We have developed the model eukaryote Saccharomyces cerevisiae as a tool to understand the mechanisms that influence ABC-transporter mediated movement of sterols. Specifically, we expressed murine ABCG1 (mABCG1) in yeast and assessed how changes in the intracellular sterol environment affect movement of sterols by this transporter. We found that expression of mABCG1 is able to vary (both increase and decrease) the concentration of exogenous sterols in the cell in response to intracellular sterol changes. We also found that yeast members of the ABCG subfamily, Aus1p and Pdr11p are able to promote either influx of cholesterol or efflux of a cholesterol derivative depending on the sterol context of the cell. This is the first example of an ABC transporter mediating bi-directional transport. These data suggest that direction of transport is not a static property of the transporter but rather can adapt in response to changes in the intracellular microenvironment. In addition to sterols we also found that proteins in the microenvironment may also influence direction of transport. Specifically, we found that the yeast sterol esterifying enzyme Are2p, physically interacts with the ABC transporters Aus1p and Pdr11p. Furthermore, all three proteins were found to co-localize to detergent resistant membrane microdomains. Deletion of either ABC transporter resulted in Are2p re-localization from DRMs to a detergent soluble fraction as well as a significant decrease in the percent of sterol esterified. This phenomenon is evolutionarily conserved in the murine lung where ABCG1 and ACAT1 were observed to co-localize with flotillin-1, a marker of DRMs. We propose that co-localization and complex formation of sterol esterification enzymes and ABC transporters in DRMs reflects a novel mechanism that directs membrane sterols to the esterification reaction. The studies presented in this thesis provide evidence that direction of transport is not a static inherent property of the transporter, but rather that it is mutable and influenced by surrounding sterols and proteins. The data provided here offers further insight as to how ABC transporters move cholesterol from the membrane and therefore may provide a platform for innovative strategies to combat atherosclerosis.
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(10725291), Priya Prakash. "Characterizing Microglial Response to Amyloid: From New Tools to New Molecules." Thesis, 2021.

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Microglia are a population of specialized, tissue-resident immune cells that make up around 10% of total cells in our brain. They actively prune neuronal synapses, engulf cellular debris, and misfolded protein aggregates such as the Alzheimer’s Disease (AD)-associated amyloid-beta (Aβ) by the process of phagocytosis. During AD, microglia are unable to phagocytose Aβ, perhaps due to the several disease-associated changes affecting their normal function. Functional molecules such as lipids and metabolites also influence microglial behavior but have primarily remained uncharacterized to date. The overarching question of this work is, How do microglia become dysfunctional in chronic inflammation? To this end, we developed new chemical tools to better understand and investigate the microglial response to Aβ in vitro and in vivo. Specifically, we introduce three new tools. (1) Recombinant human Aβ was developed via a rapid, refined, and robust method for expressing, purifying, and characterizing the protein. (2) A pH-sensitive fluorophore conjugate of Aβ (called AβpH) was developed to identify and separate Aβ-specific phagocytic and non-phagocytic glial cells ex vivo and in vivo. (3) New lysosomal, mitochondrial, and nuclei-targeting pH-activable fluorescent probes (called LysoShine, MitoShine, and NucShine, respectively) to visualize subcellular organelles in live microglia. Next, we asked, What changes occur to the global lipid and metabolite profiles of microglia in the presence of Aβ in vitro and in vivo? We screened 1500 lipids comprising 10 lipid classes and 700 metabolites in microglia exposed to Aβ. We found significant changes in specific lipid classes with acute and prolonged Aβ exposure. We also identified a lipid-related protein that was differentially regulated due to Aβ in vivo. This new lipid reprogramming mechanism “turned on” in the presence of cellular stress was also present in microglia in the brains of the 5xFAD mouse model, suggesting a generic response to inflammation and toxicity. It is well known that activated microglia induce reactive astrocytes during inflammation. Therefore, we asked, What changes in proteins, lipids, and metabolites occur in astrocytes due to their reactive state? We provide a comprehensive characterization of reactive astrocytes comprising 3660 proteins, 1500 lipids, and 700 metabolites. These microglia and astrocytes datasets will be available to the scientific community as a web application. We propose a final model wherein the molecules secreted by reactive astrocytes may also induce lipid-related changes to the microglial cell state in inflammation. In conclusion, this thesis highlights chemical neuroimmunology as the new frontier of neuroscience propelled by the development of new chemical tools and techniques to characterize glial cell states and function in neurodegeneration.

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He, Ke. "Studies of amphiphilic helical peptides interacting with lipid bilayer membranes by x-ray and neutron scattering." Thesis, 1996. http://hdl.handle.net/1911/16991.

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A variety of amphiphilic helical peptides have been shown to exhibit a transition from adsorbing parallel to a membrane surface at low concentrations to inserting perpendicularly into the membrane at high concentrations. This transition has been correlated to the peptides' cytolytic activities. Alamethicin, a 20 amino acid peptide, is an example of an amphiphilic helical peptide. Previous studies of alamethicin in diphytanoyl phosphatidylcoline (DPhPC) lipid bilayers showed that alamethicin were adsorbed in the lipid polar region at low concentrations. X-ray diffraction experiments showed that the bilayer thickness of DPhPC decreased with increasing alamethicin concentration in proportion to the peptide lipid molar ratio from 1/150 to 1/47 (Wu et al., 1995); the latter is near the threshold of the critical concentration for insertion, 1/40. This thesis will focus on the high concentration states of alamethicin in lipid bilayers. A new technique of x-ray and neutron in-plane scattering is described. With neutron in-plane scattering, the aqueous pores ($\ge20$A in diameter) formed by inserted alamethicin in lipid bilayers were directly observed. DPhPC with alamethicin at concentrations above the critical concentration for insertion was studied by x-ray lamellar diffraction. The bilayer thickness of DPhPC first decreases as the peptide begins to insert and then increases after a substantial fraction of the peptide is inserted. Huang (1995) speculated that the peptide insertion transition was caused by the membrane deformation energy. This idea is extended to the high concentration region and is used to explain qualitatively the mechanics of the peptide insertion transition.
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Books on the topic "Medical Biochemistry: Lipids"

1

J, Quinn Peter, Wang Xiaoyuan, and SpringerLink (Online service), eds. Lipids in Health and Disease. Dordrecht: Springer Science+Business Media B.V., 2008.

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Introduction to lipidomics: From bacteria to man. Boca Raton: CRC Press, 2013.

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J, McIlhinney R. A., and Hooper N. M, eds. Lipids, rafts and traffic: Biochemical Society symposium no. 72, held at BioScience2004, Glasgow, July 2004. London: Portland Press, 2005.

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D, Gunstone F., Harwood John L, and Padley F. B. 1936-, eds. The Lipid handbook. 2nd ed. London: Chapman and Hall, 1994.

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Tomohito, Hamazaki, and Okuyama Harumi, eds. Fatty acids and lipids: New findings. Basel: Karger, 2001.

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H, Ong Augustine S., and Packer Lester, eds. Lipid-soluble antioxidants: Biochemistry and clinical applications. Basel: Birkhäuser Verlag, 1992.

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ONG and PACKER. Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications. Birkhäuser, 2012.

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ONG and PACKER. Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications. Birkhauser Verlag, 2013.

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Leray, Claude. Introduction to Lipidomics: From Bacteria to Man. Taylor & Francis Group, 2012.

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Leray, Claude. Introduction to Lipidomics: From Bacteria to Man. Taylor & Francis Group, 2012.

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Book chapters on the topic "Medical Biochemistry: Lipids"

1

Blanco, Antonio, and Gustavo Blanco. "Lipids." In Medical Biochemistry, 99–119. Elsevier, 2017. http://dx.doi.org/10.1016/b978-0-12-803550-4.00005-7.

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Blanco, Antonio, and Gustavo Blanco. "Lipids." In Medical Biochemistry, 105–29. Elsevier, 2022. http://dx.doi.org/10.1016/b978-0-323-91599-1.00003-1.

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Elbein, A. D. "Complex Lipids." In Medical Biochemistry, 367–76. Elsevier, 2009. http://dx.doi.org/10.1016/b978-0-323-05371-6.00027-9.

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Baynes, J. W. "Carbohydrates and Lipids." In Medical Biochemistry, 23–32. Elsevier, 2009. http://dx.doi.org/10.1016/b978-0-323-05371-6.00003-6.

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BHAGAVAN, N. V. "Lipids III: Plasma Lipoproteins." In Medical Biochemistry, 429–51. Elsevier, 2002. http://dx.doi.org/10.1016/b978-012095440-7/50022-6.

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Aroor, AR. "Chapter-03 Chemistry of Lipids." In Medical Biochemistry, 70–100. Jaypee Brothers Medical Publishers (P) Ltd., 2011. http://dx.doi.org/10.5005/jp/books/11450_3.

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Raju, SM, and Bindu Madala. "Chemistry of Lipids." In Illustrated Medical Biochemistry, 62. Jaypee Brothers Medical Publishers (P) Ltd., 2005. http://dx.doi.org/10.5005/jp/books/10375_6.

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Bhagavan, N. V., and Chung-Eun Ha. "Lipids I." In Essentials of Medical Biochemistry, 191–207. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-12-095461-2.00016-3.

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Bhagavan, N. V., and Chung-Eun Ha. "Lipids II." In Essentials of Medical Biochemistry, 209–23. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-12-095461-2.00017-5.

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Bhagavan, N. V., and Chung-Eun Ha. "Lipids III." In Essentials of Medical Biochemistry, 225–39. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-12-095461-2.00018-7.

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