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1
Peckham, Stephen, and Niyi Awofeso. "Water Fluoridation: A Critical Review of the Physiological Effects of Ingested Fluoride as a Public Health Intervention." Scientific World Journal 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/293019.
Повний текст джерелаАнотація:
Fluorine is the world’s 13th most abundant element and constitutes 0.08% of the Earth crust. It has the highest electronegativity of all elements. Fluoride is widely distributed in the environment, occurring in the air, soils, rocks, and water. Although fluoride is used industrially in a fluorine compound, the manufacture of ceramics, pesticides, aerosol propellants, refrigerants, glassware, and Teflon cookware, it is a generally unwanted byproduct of aluminium, fertilizer, and iron ore manufacture. The medicinal use of fluorides for the prevention of dental caries began in January 1945 when community water supplies in Grand Rapids, United States, were fluoridated to a level of 1 ppm as a dental caries prevention measure. However, water fluoridation remains a controversial public health measure. This paper reviews the human health effects of fluoride. The authors conclude that available evidence suggests that fluoride has a potential to cause major adverse human health problems, while having only a modest dental caries prevention effect. As part of efforts to reduce hazardous fluoride ingestion, the practice of artificial water fluoridation should be reconsidered globally, while industrial safety measures need to be tightened in order to reduce unethical discharge of fluoride compounds into the environment. Public health approaches for global dental caries reduction that do not involve systemic ingestion of fluoride are urgently needed.
2
Kensche, A., S. Pötschke, C. Hannig, G. Richter, W. Hoth-Hannig, and M. Hannig. "Influence of Calcium Phosphate and Apatite Containing Products on Enamel Erosion." Scientific World Journal 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/7959273.
Повний текст джерелаАнотація:
For the purpose of erosion prevention the present study aimed to compare the efficacy of two biomimetic products and a fluoride solution to optimize the protective properties of the pellicle. After 1 min ofin situpellicle formation on bovine enamel slabs, 8 subjects adopted CPP-ACP (GC Tooth Mousse), a mouthwash with hydroxyapatite microclusters (Biorepair), or a fluoride based mouthwash (elmex Kariesschutz) for 1 min each. Afterwards, samples were exposed in the oral cavity for 28 min. Native enamel slabs and slabs exposed to the oral cavity for 30 min without any rinse served as controls. After oral exposure, slabs were incubated in HCl (pH values 2, 2.3, and 3) for 120 s and kinetics of calcium and phosphate release were measured photometrically; representative samples were evaluated by SEM and TEM. The physiological pellicle reduced demineralization at all pH values; the protective effect was enhanced by fluoride. The biomimetic materials also reduced ion release but their effect was less pronounced. SEM indicated no layer formation after use of the different products. However, TEM confirmed the potential accumulation of mineral components at the pellicle surface. The tested products improve the protective properties of thein situpellicle but not as effectively as fluorides.
3
Sauerheber, Richard. "Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride." Journal of Environmental and Public Health 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/439490.
Повний текст джерелаАнотація:
The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.
4
Lisjak, Darja, Maša Vozlič, Uliana Kostiv, Daniel Horák, Boris Majaron, Slavko Kralj, Irena Zajc, Lovro Žiberna, and Maja Ponikvar-Svet. "NaYF4-based upconverting nanoparticles with optimized phosphonate coatings for chemical stability and viability of human endothelial cells." Methods and Applications in Fluorescence 10, no. 1 (December 22, 2021): 014001. http://dx.doi.org/10.1088/2050-6120/ac41ba.
Повний текст джерелаАнотація:
Abstract The increasing interest in upconverting nanoparticles (UCNPs) in biodiagnostics and therapy fuels the development of biocompatible UCNPs platforms. UCNPs are typically nanocrystallites of rare-earth fluorides codoped with Yb3+ and Er3+ or Tm3+. The most studied UCNPs are based on NaYF4 but are not chemically stable in water. They dissolve significantly in the presence of phosphates. To prevent any adverse effects on the UCNPs induced by cellular phosphates, the surfaces of UCNPs must be made chemically inert and stable by suitable coatings. We studied the effect of various phosphonate coatings on chemical stability and in vitro cytotoxicity of the Yb3+,Er3+-codoped NaYF4 UCNPs in human endothelial cells obtained from cellular line Ea.hy926. Cell viability of endothelial cells was determined using the resazurin-based assay after the short-term (15 min), and long-term (24 h and 48 h) incubations with UCNPs dispersed in cell-culture medium. The coatings were obtained from tertaphosphonic acid (EDTMP), sodium alendronate and poly(ethylene glycol)-neridronate. Regardless of the coating conditions, 1 − 2 nm-thick amorphous surface layers were observed on the UCNPs with transmission electron microscopy. The upconversion fluorescence was measured in the dispersions of all UCNPs. Surafce quenching in aqueous suspensions of the UCNPs was reduced by the coatings. The dissolution degree of the UCNPs was determined from the concentration of dissolved fluoride measured with ion-selective electrode after the ageing of UCNPs in water, physiological buffer (i.e., phosphate-buffered saline—PBS) and cell-culture medium. The phosphonate coatings prepared at 80 °C significantly suppressed the dissolution of UCNPs in PBS while only minor dissolution of bare and coated UCNPs was measured in water and cell-culture medium. The viability of human endothelial cells was significantly reduced when incubated with UCNPs, but it increased with the improved chemical stability of UCNPs by the phosphonate coatings with negligible cytotoxicity when coated with EDTMP at 80 °C.
5
Clarkson, B. H. "Caries Prevention Fluoride." Advances in Dental Research 5, no. 1 (December 1991): 41–45. http://dx.doi.org/10.1177/08959374910050010501.
Повний текст джерелаАнотація:
A clear understanding of the mechanism of action of fluoride and its pharmacokinetics would ensure appropriate clinical use of fluoride and fluoride-containing modalities. Convincing evidence exists that fluoride has a major effect on the demineralization and remineralization of dental hard tissues, and that it interferes with the acid production from "cariogenic" bacteria. However, it has also been shown to be physiologically harmful if fluoride concentrations and/or exposure periods are inappropriate. In order to establish appropriate clinical concentrations and exposure periods for fluoride administration, this review is concentrated on the theme that fluoride controls but does not prevent caries. The review is organized along classical lines, with a discussion of the role of systemic vs. topical fluoride. Discussion of the systemic effects of fluoride includes ingestion through water fluoridation, fluoride supplements, topical fluoride applications, and dentifrices. The benefits and problems associated with the systemic route of fluoride administration are discussed with special reference to caries control and fluoride's mechanism of action and its toxic effect. The same discussions are focused on the role of the topical effects of fluoride, with particular emphasis placed upon: low vs. high fluoride concentrations; calcium fluoride vs. fluorhydroxyapatite; and fluoride distribution, in both the mouth and in the teeth.
6
PELC, Justyna, Beata SMOLIK, and Marcelina KRUPA-MAŁKIEWICZ. "EFFECT OF SODIUM FLUORIDE ON SOME MORPHOLOGICAL AND PHYSIOLOGICAL PARAMETERS OF 10-DAY-OLD SEEDLINGS OF VARIOUS PLANT SPECIES." Folia Pomeranae Universitatis Technologiae Stetinensis Agricultura, Alimentaria, Piscaria et Zootechnica 338, no. 44 (December 30, 2017): 151–58. http://dx.doi.org/10.21005/aapz2017.44.4.16.
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7
Bagmut, I. Yu, and I. L. Kolisnyk. "EFFECT OF FLUORIDE INTOXICATION ON HISTOHORMONE CONTENT IN EXPERIMENTS." Здобутки клінічної і експериментальної медицини, no. 4 (February 12, 2021): 13–16. http://dx.doi.org/10.11603/1811-2471.2020.v.i4.11751.
Повний текст джерелаАнотація:
Connection of work with scientific plans, topics. The work was performed in accordance with the research plan of the Kharkiv Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine and is a fragment of research work of the Department of Clinical Pathophysiology, Topographic Anatomy and Operative Surgery "Pathophysiological mechanisms of radiotoxins on the body and principles of early diagnosis 2017–2021).
SUMMARY. One of the important medical and biological problems is to elucidate the physiological and molecular mechanisms of the impact of harmful environmental factors on the body, including fluorine and its compounds, in particular sodium fluoride [1].
Solving this problem is of great theoretical and practical importance for understanding the intracellular defense mechanisms of the organism. Close attention to various aspects of the biological effects of fluoride on the body is due to the significant distribution of this halogen in nature. At physiological concentrations, it is necessary for normal growth and development of the organism, where it performs its specific metabolic function. Any changes in the external and internal environment are accompanied by changes in the function of the endocrine glands, which leads to certain changes in metabolism and energy. It is known that hormonal insufficiency is accompanied by a decrease in the body's resistance to various adverse factors, including physical, biological, chemical. Disturbance of hormone balance and functioning of endocrine organs and systems entails profound changes in metabolic processes and immunobiological reactivity of the organism, weakening of adaptive-protective mechanisms in support of homeostatic function [2,3]. It is important to study the effects of subchronic fluoride intake, which can in a relatively short time cause various intracellular and systemic disorders in the body.
8
Jakubczyk, Karolina, Alicja Ligenza, Izabela Gutowska, and Katarzyna Janda-Milczarek. "Fluoride Content of Matcha Tea Depending on Leaf Harvest Time and Brewing Conditions." Nutrients 14, no. 12 (June 20, 2022): 2550. http://dx.doi.org/10.3390/nu14122550.
Повний текст джерелаАнотація:
Matcha, or powdered green tea (Camellia sinensis) of the Tencha type, is popular all around the world, and its consumption continues to rise. Because of its unique cultivation method, it is rich in phytochemicals and has many health-promoting properties; it contains high concentrations of polyphenols, theanine and chlorophyll. Tea, and by extension matcha, contains numerous minerals, one of which is fluorine. Under physiological conditions, this mineral plays a significant role in hard tissue mineralisation processes. However, even in low concentrations, with prolonged exposure, fluoride can accumulate in the body, leading to a number of harmful effects. The aim of this study was to evaluate, for the first time, the fluoride content of the matcha infusions from different harvests, brewed using water at different temperatures (25 °C, 70 °C, 80 °C and 90 °C). The content of fluoride ions was measured by the potentiometric method. The fluoride content ranged from 3.36 to 4.03 mg/L and was dependent on both the leaf harvest time and brewing temperature. The concentration of this mineral in the dry powder ranged from 118.39 to 121.65 mg/kg. Irrespective of the water temperature or harvest time, matcha was found to have a high fluoride content, with particularly high concentrations being noted in the powder itself.
9
Whitford, G. M., D. W. Allmann, and A. R. Shahed. "Topical Fluorides: Effects on Physiologic and Biochemical Processes." Journal of Dental Research 66, no. 5 (May 1987): 1072–78. http://dx.doi.org/10.1177/00220345870660051801.
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10
Rodrigues, Douglas Almeida, Juliana de Fátima Sales, Sebastião Carvalho Vasconcelos Filho, Arthur Almeida Rodrigues, Eduardo Matheus Guimarães Teles, Alan Carlos Costa, Efraim Lázaro Reis, Thais Andrade de Carvalho Silva, and Caroline Müller. "Bioindicator potential of Ricinus communis to simulated rainfall containing potassium fluoride." PeerJ 8 (July 1, 2020): e9445. http://dx.doi.org/10.7717/peerj.9445.
Повний текст джерелаАнотація:
Background Fluoride pollution is a global problem because of its high phytotoxicity. Fluoride is released in air, water and soil through industrial processes, where it damages various plant species. Ricinus communis is widely distributed in Brazil, India and China and has been extensively used as a phytoremediation species in heavy metal-contaminated soils. However, few studies regarding the effect of air pollutants on R. communis have been published, and no information about the exposure of this species to fluoride is available. Therefore, the aim of the present study was to investigate the effects of fluoride on R. communis morphoanatomical and physiological responses using simulated rainfall containing potassium fluoride (KF). Methods Young plants at approximately 10 days after emergence were treated daily with KF using simulated rainfall at 0, 1.5, 3.0 and 4.5 mg L−1, for 37 consecutive days. Chlorophyll a fluorescence, gas exchange, anatomical characteristics and fluoride accumulation in the roots and leaves were evaluated after this period. Results No visual or anatomical symptoms were observed for the first three treatments. Necrosis and chlorosis were visually evident after the 37th day of KF application at 4.5 mg L−1, followed by changes in parenchyma tissues, cell collapse and phenolic compound accumulation at the end of the experiment. No damage was observed in terms of photosynthetic photochemical and biochemical stages. Maintenance of physiological characteristics in the presence of fluoride accumulation in roots and leaves were shown to be important fluoride biomarkers. These characteristics suggest that R. communis is tolerant to 1.5 and 3.0 mg L−1 KF, and is anatomically sensitive at 4.5 mg L−1 KF.
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Lima-Filho, Guilherme L., Glaydes M. T. Lima, Silvana R. F. Moreno, Luiz C. M. Aleixo, Sebastião D. Santos-Filho, Rosimeire S. Freitas, Vilma G. B. Melo, and Mario Bernardo-Filho. "Physiological (osmotic fragility) and morphological effects on red blood cells: action of phytic acid and stannous fluoride." Canadian Journal of Physiology and Pharmacology 82, no. 12 (December 1, 2004): 1091–95. http://dx.doi.org/10.1139/y04-110.
Повний текст джерелаАнотація:
Phytic acid occurs in foods derived from plants. We have investigated the possibility that phytic acid and stannous fluoride are capable of altering the physiological properties (osmotic fragility) and morphological properties of red blood cells (RBC). Osmotic fragility was unchanged by the presence of phytic acid and stannous fluoride in the studied concentrations, but RBC morphology was modified in the presence of the studied substances. In conclusion, the alterations to RBC morphology were not sufficient to promote modifications in osmotic fragility. Our results suggest that the chelating properties of phytic acid could be responsible for the observed effects.Key words: phytic acid, stannous fluoride, morphology, osmotic fragility.
12
Tanimoto, K., T. Le, L. Zhu, J. Chen, J. D. B. Featherstone, W. Li, and P. DenBesten. "Effects of Fluoride on the Interactions between Amelogenin and Apatite Crystals." Journal of Dental Research 87, no. 1 (January 2008): 39–44. http://dx.doi.org/10.1177/154405910808700106.
Повний текст джерелаАнотація:
Fluorosed enamel is more porous and less mineralized, possibly related to altered amelogenin-modulated crystal growth. The purpose of this study was to examine the role of fluoride in interactions between amelogenin and apatite crystals. Recombinant human amelogenin (rh174) was bound to carbonated hydroxyapatite containing various amounts of fluoride, and analyzed by protein assay, SDS PAGE, and AFM. Interactions between rh174 and fluoride were assayed by isothermal titration calorimetry (ITC). The initial binding rate of rh174, as well as total amount of rh174 bound to fluoride-containing carbonated hydroxyapatite, was greater than that in the control carbonated hydroxyapatite. Fluoride in solution at physiologic (5.3 micromolar, or 0.1 ppm) concentrations showed no significant effect on binding, but higher fluoride levels significantly decreased protein binding. ITC showed no interactions between fluoride and rh174. These results suggest that fluoride incorporation into the crystal lattice alters the crystal surface to enhance amelogenin binding, with no direct interactions between fluoride and amelogenin.
13
Maressa Hungria de Lima e Silva, Ingrid, Arthur Almeida Rodrigues, Juliana de Fátima Sales, Douglas Almeida Rodrigues, Sebastião Carvalho Vasconcelos Filho, Cássia Lino Rodrigues, Priscila Ferreira Batista, et al. "Fluoride effect indicators in Phaseolus vulgaris seeds and seedlings." PeerJ 10 (May 17, 2022): e13434. http://dx.doi.org/10.7717/peerj.13434.
Повний текст джерелаАнотація:
Background Fluoride (F) is one of the main environmental pollutants, and high concentrations are commonly detected in the air and in both surface and groundwater. However, the effects of this pollutant on seed germination and on the initial growth of crop seedlings are still poorly understood. In this context, the aim of this study was to assess morphoanatomical, physiological and biochemical fluoride effect indicators in Phaseolus vulgaris L. seeds and seedlings. Methods P. vulgaris seeds were exposed to a liquid potassium fluoride solution (KF, pH 6.0) at concentrations of 0 (control), 10, 20, 30 mg L−1 for 7 days. A completely randomized experimental design was applied, consisting of four treatments with four replications each. During the experimental period, physiological (7 days) anatomical and histochemical (2 days), biochemical and chemical (4 days) assessments. An analysis of variance was performed followed by Dunnett’s test. to determine significant differences between the KF-exposed groups and control seeds; and a multivariate analysis was performed. Results The germination parameters, and anatomical, morphological, physiological, biochemical and nutritional characteristics of the seedlings did not show negative effects from exposure to KF at the lowest doses evaluated. On the other hand, treatment with the highest dose of KF (30 mg L−1) resulted in a lower germination rate index and increase in abnormal seedlings, and higher electrical conductivity. A lower root length, magnesium content and photochemical efficiency were also observed. The exposure of P. vulgaris to KF, regardless the dose did not affect seeds anatomy and the accumulation of starch and proteins, in relation to the control group. Conclusions Our findings demonstrated that P. vulgaris seedlings were tolerant to KF solutions up to 20 mg L−1, and sensitive when exposed to 30 mg KF L−1.
14
ten Cate, J. M., and J. D. B. Featherstone. "Mechanistic Aspects of the Interactions Between Fluoride and Dental Enamel." Critical Reviews in Oral Biology & Medicine 2, no. 3 (July 1991): 283–96. http://dx.doi.org/10.1177/10454411910020030101.
Повний текст джерелаАнотація:
For many years after the discovery of its caries preventive effect, fluoride was thought to be primarily active by lowering the solubility of the apatitic mineral phase of the dental hard tissues. Recent findings have shed new light on the mechanisms by which fluoride inhibits or delays dental caries. Fluoride present in the oral fluids alters the rate of the naturally occurring dissolution and reprecipitation processes at the tooth-oral fluid interface. Demineralization of enamel is inhibited by concentrations of fluoride in the sub-ppm range. Likewise, remineralization of incipient caries lesions (the earliest stage of enamel caries) is accelerated by trace amounts of fluoride. As these two processes comprise dental caries the physiological balance between hard tissue breakdown and repair is favorably shifted by fluoride. The driving force for both phenomena is thermodynamic, that is, fluorapatite or a fluoridated hydroxyapatite may form when fluoride is supplied at low concentrations. This article critically reviews the current information about tooth-fluoride interactions, both from laboratory and clinical studies.
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Almeida Rodrigues, Arthur, Douglas Almeida Rodrigues, Juliana de Fátima Sales, Sebastião Carvalho Vasconcelos Filho, Alan Carlos Costa, Cássia Lino Rodrigues, Adinan Alves da Silva, Marisa Domingos, and Caroline Müller. "Morphoanatomical, Physiological, and Biochemical Indicators in Lactuca sativa L. Germination and Growth in Response to Fluoride." Plants 11, no. 23 (December 6, 2022): 3406. http://dx.doi.org/10.3390/plants11233406.
Повний текст джерелаАнотація:
Fluoride is one of the main phytotoxic environmental pollutants, and high concentrations (10–30 mg L−1) are commonly detected in surface and groundwater. Little, however, is known about the effects of this pollutant on crops that require irrigation during their development, which, in addition to phytotoxicity, may cause negative human health effects. Thus, the aim of this study was to characterize the effects of potassium fluoride (KF) on the germination of lettuce seeds and identify the physiological and anatomical markers of this pollutant’s action on plants exposed to it during growth. Initially, lettuce seeds were sown in gerboxes and soaked in solutions containing 0 mg L−1, 10 mg L−1, 20 mg L−1, and 30 mg L−1 KF. Plants grown in a greenhouse were treated daily with KF irrigation at the same KF concentrations for 40 days. KF exposure reduced the germination rate and germination speed index of lettuce seeds at 20 mg L−1 and 30 mg L−1, resulting in compromised root development at the highest KF concentration. Lettuce plants displayed a slight photosynthesis reduction and a significant photochemical efficiency decrease after exposures to all KF concentrations. Lower chlorophyll contents and nitrogen balance indices were observed in plants exposed to 30 mg L−1 KF. On the other hand, increases in phenolic compounds and malondialdehyde were noted with increasing KF concentrations. Lettuce plants can, therefore, accumulate fluoride in leaves when irrigated with KF-rich water. The investigated physiological and biochemical variables were proven to be adequate fluoride action biomarkers in lettuce plants and may become an important tool in the study of olericulture contaminants.
16
Nakada, M. T., J. M. Stadel та S. T. Crooke. "Mobilization of extracellular Ca2+ by prostaglandin F2α can be modulated by fluoride in 3T3-L1 fibroblasts". Biochemical Journal 272, № 1 (15 листопада 1990): 167–74. http://dx.doi.org/10.1042/bj2720167.
Повний текст джерелаАнотація:
Changes in the intracellular concentration of calcium [(Ca2+]i) have been shown to mediate the physiological effects of certain agonists. Ca2+ mobilization occurs through multiple mechanisms which involve both influx and internal release of Ca2+. Prostaglandin F2 alpha (PGF2 alpha) caused a transient mobilization of intracellular Ca2+ in 3T3-L1 fibroblasts. This effect was characterized by fluorescence measurements of trypsin-treated cells loaded with fura-2/AM. In the absence of extracellular Ca2+, the peak amount of Ca2+ mobilized by PGF2 alpha was decreased by 70%, a lag time before the onset of [Ca2+]i increase was observed, and the rate of rise of [Ca2+]i was slowed. Addition of NaF (10 mM) to fura-2-loaded 3T3-L1 cells caused a dose-dependent increase in [Ca2+]i after a brief (approximately 10 s) lag. Maximal effects (approximately 300 nM) were observed at 5-10 mM-NaF. This effect was dependent on the presence of extracellular Ca2+ and appeared to be independent of inositol phosphate production. After reaching a peak at around 40 s after fluoride addition, [Ca2+]i returned to near-baseline within 120 s. This return of [Ca2+]i to near-baseline after fluoride stimulation and the inability of the cells to respond to a subsequent addition of fluoride indicated that the response to fluoride underwent desensitization. Similarly, the pathway used by PGF2 alpha to mobilize Ca2+ underwent desensitization. Exposure of the cells to a maximally effective concentration of fluoride and subsequent addition of PGF2 alpha produced a [Ca2+]i response to PGF2 alpha which was similar in magnitude and kinetics to that seen for PGF2 alpha in the absence of extracellular Ca2+. Conversely, prior exposure of cells to PGF2 alpha diminished the ability of fluoride to mobilize Ca2+. PGF2 alpha also increased inositol phosphate formation, with a time course and dose-response consistent with its ability to increase [Ca2+]i. Prior exposure of cells to fluoride did not change the time course or dose-response characteristics of PGF2 alpha-induced generation of inositol phosphates. These data suggest that PGF2 alpha and fluoride share a common mechanism of activating Ca2+ influx in 3T3-L1 cells.
17
Pan, Ye, Peng Lü, Lijing Yin, Keping Chen, and Yuanqing He. "Effect of fluoride on the proteomic profile of the hippocampus in rats." Zeitschrift für Naturforschung C 70, no. 5-6 (May 1, 2015): 151–57. http://dx.doi.org/10.1515/znc-2014-4158.
Повний текст джерелаАнотація:
Abstract Two-dimensional gel electrophoresis (2-DE) was used to detect fluoride-induced alterations in the proteome of the rat hippocampus. Male Sprague-Dawley rats (n=30) were subjected to treatments three weeks after weaning. Animals of the first group were injected intraperitoneally (i.p.) with aqueous NaF (20 mg/kg/body weight/day), the second group, injected with physiological saline, served as the control. After 30 days, the body weight of the fluoride-treated rats was lower than that of the control, and F– levels in serum were higher than in the control. The hippocampus was subjected to proteomic analysis, and the fluoride-treated group was found to contain 19 up-regulated and eight down-regulated proteins. The proteins, identified by mass-spectroscopic analysis of their fragments obtained after digestion, were found to be involved in amino acid biosynthesis, the insulin signaling pathway and various other crucial functions. Our results also provide useful information on the mechanism of the reduction of the learning ability and memory induced by F.
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Silla, Josué M., Claudimar J. Duarte, Rodrigo A. Cormanich, Roberto Rittner, and Matheus P. Freitas. "Conformational analysis of 2,2-difluoroethylamine hydrochloride: double gauche effect." Beilstein Journal of Organic Chemistry 10 (April 16, 2014): 877–82. http://dx.doi.org/10.3762/bjoc.10.84.
Повний текст джерелаАнотація:
The gauche effect in fluorinated alkylammonium salts is well known and attributed either to an intramolecular hydrogen bond or to an electrostatic attraction between the positively charged nitrogen and the vicinal electronegative fluorine atom. This work reports the effect of adding a fluorine atom in 2-fluoroethylamine hydrochloride on the conformational isomerism of the resulting 2,2-difluoroethylamine chloride (2). The analysis was carried out using NMR coupling constants in D2O solution, in order to mimic the equilibrium conditions in a physiological medium, in the gas phase and in implicit water through theoretical calculations. Despite the presence of σCH→σ*CF and σCH→σ*CN interactions, which usually rule the hyperconjugative gauche effect in 1,2-disubstituted ethanes, the most important forces leading to the double gauche effect (+NH3 in the gauche relationship with both fluorine atoms) in 2 are the Lewis-type ones. Particularly, electrostatic interactions are operative even in water solution, where they should be significantly attenuated, whereas hyperconjugation and hydrogen bond have secondary importance.
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Anusavice, K. J. "Degradability of Dental Ceramics." Advances in Dental Research 6, no. 1 (September 1992): 82–89. http://dx.doi.org/10.1177/08959374920060012201.
Повний текст джерелаАнотація:
The degradation of dental ceramics generally occurs because of mechanical forces or chemical attack. The possible physiological side-effects of ceramics are their tendency to abrade opposing dental structures, the emission of radiation from radioactive components, the roughening of their surfaces by chemical attack with a corresponding increase in plaque retention, and the release of potentially unsafe concentrations of elements as a result of abrasion and dissolution. The chemical durability of dental ceramics is excellent. With the exception of the excessive exposure to acidulated fluoride, ammonium bifluoride, or hydrofluoric acid, there is little risk of surface degradation of virtually all current dental ceramics. Extensive exposure to acidulated fluoride is a possible problem for individuals with head and/or neck cancer who have received large doses of radiation. Such fluoride treatment is necessary to minimize tooth demineralization when saliva flow rates have been reduced because of radiation exposure to salivary glands. Porcelain surface stains are also lost occasionally when abraded by prophylaxis pastes and/or acidulated fluoride. In each case, the solutes are usually not ingested. Further research that uses standardized testing procedures is needed on the chemical durability of dental ceramics. Accelerated durability tests are desirable to minimize the time required for such measurements. The influence of chemical durability on surface roughness and the subsequent effect of roughness on wear of the ceramic restorations as well as of opposing structures should also be explored on a standardized basis.
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Mirzakarimova, Malokhat A. "COMPARATIVE ANALYSIS OF THE INFLUENCE OF COMPLEX MIXTURES OF CHEMICAL AIR POLLUTANTS ON BIOCHEMICAL, PHYSIOLOGICAL, GONADO-, EMBRYOTOXIC INDICES OF LABORATORY ANIMALS AND HYGIENIC EVALUATION OF THEIR COMBINED ACTION." Hygiene and sanitation 96, no. 6 (March 27, 2019): 528–31. http://dx.doi.org/10.18821/0016-9900-2017-96-6-528-531.
Повний текст джерелаАнотація:
In the paper there are presented results of experimental works on the study of the character of the combined toxic effect of various complex mixtures presenting in atmospheric air. The action of complex mixtures on the organism of laboratory animals was studied in two series of experiments. In the first series of the experiments there was investigated the combined action of sulfur dioxide, nitrogen dioxide, hydrogen fluoride and suspended substances, and in the second series of experiments - of lead acetate, formaldehyde, sulfur dioxide and ammonia.The character of the combined action of lead acetate, formaldehyde, sulfur dioxide, ammonia under one-term inhalation is established to be manifested in the form of “effect-summation”, and the impact of such suspended substances as hydrogen fluoride, sulfur dioxide, nitrogen dioxide was similar to the type of “incomplete summation”. In the joint presence of lead acetate, formaldehyde, sulfur dioxide, ammonia in the ambient air, the maximum permissible concentration (MPC ) for each substance should not exceed 0.25 MPC, and the hydrogen fluoride, nitrogen dioxide, sulfur dioxide and suspended solids should not exceed 0.46 MPC under their isolated action .
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Fan, Jibiao, Ke Chen, Jilei Xu, Khaldun ABM, Yao Chen, Liang Chen, and Xuebing Yan. "Physiological effects induced by aluminium and fluoride stress in tall fescue (Festuca arundinacea Schreb)." Ecotoxicology and Environmental Safety 231 (February 2022): 113192. http://dx.doi.org/10.1016/j.ecoenv.2022.113192.
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Duncan, R. F., and J. W. Hershey. "Initiation factor protein modifications and inhibition of protein synthesis." Molecular and Cellular Biology 7, no. 3 (March 1987): 1293–95. http://dx.doi.org/10.1128/mcb.7.3.1293-1295.1987.
Повний текст джерелаАнотація:
The protein covalent modification state of eucaryotic initiation factors eIF-2 and eIF-4B in HeLa cells was examined after they were exposed to a variety of conditions or treatments that regulate protein synthesis. A few factors (e.g., variant pH and sodium fluoride) altered the phosphorylation state of the initiation factor proteins, but the majority (hypertonic medium, ethanol, dimethyl sulfoxide sodium selenite, sodium azide, and colchicine) had no effect on either protein. While initiation factor phosphorylation may regulate protein synthesis in response to many physiological situations, other pathways can regulate protein synthesis under nonphysiological circumstances.
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Duncan, R. F., and J. W. Hershey. "Initiation factor protein modifications and inhibition of protein synthesis." Molecular and Cellular Biology 7, no. 3 (March 1987): 1293–95. http://dx.doi.org/10.1128/mcb.7.3.1293.
Повний текст джерелаАнотація:
The protein covalent modification state of eucaryotic initiation factors eIF-2 and eIF-4B in HeLa cells was examined after they were exposed to a variety of conditions or treatments that regulate protein synthesis. A few factors (e.g., variant pH and sodium fluoride) altered the phosphorylation state of the initiation factor proteins, but the majority (hypertonic medium, ethanol, dimethyl sulfoxide sodium selenite, sodium azide, and colchicine) had no effect on either protein. While initiation factor phosphorylation may regulate protein synthesis in response to many physiological situations, other pathways can regulate protein synthesis under nonphysiological circumstances.
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Rai, L. C., Y. Husaini, and N. Mallick. "Physiological and biochemical responses of Nostoc linckia to combined effects of aluminium, fluoride and acidification." Environmental and Experimental Botany 36, no. 1 (May 1996): 1–12. http://dx.doi.org/10.1016/0098-8472(95)00049-6.
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Batra, Akriti, and Vabitha Shetty. "Non-Fluoridated Remineralising Agents - A Review of Literature." Journal of Evolution of Medical and Dental Sciences 10, no. 9 (March 1, 2021): 638–44. http://dx.doi.org/10.14260/jemds/2021/136.
Повний текст джерелаАнотація:
Dental caries is not merely a continuous and one-way process of demineralisation of the mineral phase, but repeated episodes of demineralisations and remineralisation. The remineralisation process is a natural repair mechanism to restore the minerals again, in ionic forms, to the hydroxyapatite (HAP) crystal lattice. It occurs under nearneutral physiological pH conditions whereby calcium and phosphate mineral ions are redeposited within the caries lesion from saliva and plaque fluid resulting in the formation of newer HAP crystals, which are larger and more resistant to acid dissolution. An insight into the caries process’s multifactorial aetiopathogenesis has resulted in a paradigm shift towards minimally invasive dentistry. This era of personalised care using the medical model for caries management assimilates the signs of examining, diagnosing, intercepting, and managing dental caries at a microscopic level. Fluoride mediated salivary remineralisation system is considered the cornerstone of non-invasive approach for managing non-cavitated carious lesions. However, the effect of fluoride was found to be limited to the outer surface of the tooth, and it was observed that fluoride does not influence the modifiable factors in dental caries such as the biofilm. Hence, fluoride does not reduce the cariogenic challenge especially for high-risk individuals. Due to this gap in the conventional fluoride therapies, non-fluoridated remineralising systems have emerged, which interact with the tooth by delivering calcium and phosphorous ions, modifying the biofilm and neutralising the organic acids. This review re-examines the philosophy behind non-fluoridated remineralisation, their mode of action, availability in the market and evidence-based studies of the most promising advancements in remineralisation approaches. KEY WORDS Caries, Minimally Invasive Dentistry, Remineralisation, Non-Fluoridated Remineralising Systems
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Kumar, Abhishek, Lallu, Munna Singh, and Krishan K. Verma. "Phytotoxicity of Fluoride in Guar (Cyamopsis tetragonoloba) Cultivars and its Effect on Morpho-Physiological and Biochemical Traits." Indian Journal of Agricultural Biochemistry 29, no. 2 (2016): 219. http://dx.doi.org/10.5958/0974-4479.2016.00035.6.
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Goenka, Shilpi, and Sanford R. Simon. "Effects of Fluoride Exposure on Primary Human Melanocytes from Dark and Light Skin." Toxics 8, no. 4 (December 2, 2020): 114. http://dx.doi.org/10.3390/toxics8040114.
Повний текст джерелаАнотація:
Fluoride exposure has adverse effects on human health that have been studied in vitro in cell culture systems. Melanocytes are the melanin pigment-producing cells that have a significant role in the regulation of the process of melanogenesis, which provides several health benefits. Melanocytes are present in the oral cavity, skin, brain, lungs, hair, and eyes. However, to date, there has been no study on the effects of fluoride exposure on melanocytes. Hence, in the current study, we have studied the effects of sodium fluoride (NaF) exposure on neonatal human epidermal melanocytes (HEMn) derived from two different skin phototypes, lightly pigmented (LP) and darkly pigmented (DP). We have assessed the impact of a 24 h and 72 h NaF exposure on metabolic activity and membrane integrity of these cells. In addition, we have evaluated whether NaF exposure might have any impact on the physiological functions of melanocytes associated with the production of melanin, which is regulated by activity of the enzyme tyrosinase. We have also assessed if NaF exposure might induce any oxidative stress in LP and DP melanocytes, by evaluation of production of reactive oxygen species (ROS) and measurement of mitochondrial membrane potential (MMP) levels. Our results showed that HEMn-LP cells showed a higher sensitivity to NaF cytotoxicity than HEMn-DP cells, with significant cytotoxicity at concentrations >1 mM, while concentration range 0.25–1 mM were nontoxic and did not lead to oxidative stress, and also did not alter the levels of intracellular melanin or cellular tyrosinase activity, indicating that treatment up to 1 mM NaF is generally safe to melanocytes from both pigmentation phototypes.
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Lv, Kui Long, Jiu Xing Zhang, Xiang Cai Meng, and Xing Yi Li. "Remineralization Effect of the Nano-HA Toothpaste on Artificial Caries." Key Engineering Materials 330-332 (February 2007): 267–70. http://dx.doi.org/10.4028/www.scientific.net/kem.330-332.267.
Повний текст джерелаАнотація:
The aim of this study is to describe the remineralization effect of the nano-HA toothpaste on artificial caries. The artificial dental caries is made using sour solution. The demineralized teeth specimen is put into five kinds of toothpaste solution respectively for 5 days and 10 days, which are: solution of containing needle like nano-HA, solution of containing spherical nano-HA, solution of general HA, fluorine sodium solution and physiological saline. The hardness of specimen is measured and the surface morphology is characterized by SEM. The remineralized test indicates that the nano-HA toothpaste can enhance the hardness of artificial caries and improve the remineralization of artificial caries. The SEM analysis shows that the cavities and defects of enamel surface are decreased and many mineral salts are sedimentated, which indicate that the nano-HA could promote remineralization for the demineralized enamel.
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Eanes, E. D., and A. W. Hailer. "The Effect of Fluoride on the Size and Morphology of Apatite Crystals Grown from Physiologic Solutions." Calcified Tissue International 63, no. 3 (September 1998): 250–57. http://dx.doi.org/10.1007/s002239900522.
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Pereda, M. D., C. Alonso, M. Gamero, J. A. del Valle, and M. Fernández Lorenzo de Mele. "Comparative study of fluoride conversion coatings formed on biodegradable powder metallurgy Mg: The effect of chlorides at physiological level." Materials Science and Engineering: C 31, no. 5 (July 2011): 858–65. http://dx.doi.org/10.1016/j.msec.2011.01.010.
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CADEFAU, Joan, Mathieu BOLLEN, and Willy STALMANS. "Glucose-induced glycogenesis in the liver involves the glucose-6-phosphate-dependent dephosphorylation of glycogen synthase." Biochemical Journal 322, no. 3 (March 15, 1997): 745–50. http://dx.doi.org/10.1042/bj3220745.
Повний текст джерелаАнотація:
Non-metabolized glucose derivatives may cause inactivation of phosphorylase but, unlike glucose, they are unable to elicit activation of glycogen synthase in isolated hepatocytes. We report here that, after the previous inactivation of phosphorylase by one of these glucose derivatives (2-deoxy-2-fluoro-α-glucosyl fluoride), glycogen synthase was progressively activated by addition of increasing concentrations of glucose. Under these conditions, the degree of activation of glycogen synthase was linearly correlated with the intracellular glucose-6-phosphate (Glc-6-P) concentration. Addition of glucosamine, an inhibitor of glucokinase, decreased both parameters in parallel. Further experiments using an inhibitor of either protein kinases (5-iodotubercidin) or protein phosphatases (microcystin) in isolated hepatocytes indicated that Glc-6-P does not affect glycogen-synthase kinase activity but enhances the glycogen-synthase phosphatase reaction. Experiments in vitro showed that the synthase phosphatase activity of glycogen-bound type-1 protein phosphatase was increased by physiological concentrations of Glc-6-P (0.1–0.5 mM), but not by 2.5 mM fructose-6-P, fructose-1-P or glucose-1-P. At physiological ionic strength, the glycogen-associated synthase phosphatase activity was nearly entirely Glc-6-P-dependent, but Glc-6-P did not relieve the strong inhibitory effect of phosphorylase a. The large stimulatory effects of 2.5 mM Glc-6-P, with glycogen synthase b and phosphorylase a as substrates, appeared to be mostly substrate-directed, while the modest effects observed with casein and histone IIA pointed to an additional stimulation of glycogen-bound protein phosphatase-1 by Glc-6-P. We conclude that glucose elicits hepatic synthase phosphatase activity both by removal of the inhibitor, phosphorylase a, and by generation of the stimulator, Glc-6-P.
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Kruse, Anne Brigitte, Nadine Schlueter, Viktoria Konstanze Kortmann, Cornelia Frese, Annette Anderson, Annette Wittmer, Elmar Hellwig, Kirstin Vach, and Ali Al-Ahmad. "Long-Term Use of Oral Hygiene Products Containing Stannous and Fluoride Ions: Effect on Viable Salivary Bacteria." Antibiotics 10, no. 5 (April 22, 2021): 481. http://dx.doi.org/10.3390/antibiotics10050481.
Повний текст джерелаАнотація:
The aim of this randomized, controlled clinical trial was to isolate and identify viable microorganisms in the saliva of study participants that continuously used a stannous and fluoride ion (F/Sn)-containing toothpaste and mouth rinse over a period of three years in comparison to a control group that used stannous ion free preparations (noF/Sn) over the same time period. Each group (F/Sn and noF/Sn) included 16 participants that used the respective oral hygiene products over a 36-month period. Stimulated saliva samples were collected at baseline (T0) and after 36 months (T1) from all participants for microbiological examination. The microbial composition of the samples was analyzed using culture technique, matrix-assisted laser desorption ionization–time of flight (MALDI–TOF) mass spectrometry, and 16S rDNA Polymerase Chain Reaction (PCR). There were only minor differences between both groups when comparing the absolute values of viable microbiota and bacterial composition. The treatment with F/Sn led to a slight decrease in disease-associated and a slight increase in health-associated bacteria. It was shown that the use of stannous ions had no negative effects on physiological oral microbiota even after prolonged use. In fact, a stabilizing effect of the oral hygiene products containing stannous ions on the health-associated oral microbiota could be expected.
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Mao, Yupeng, Wen Yue, Tianming Zhao, MaiLun Shen, Bing Liu, and Song Chen. "A Self-Powered Biosensor for Monitoring Maximal Lactate Steady State in Sport Training." Biosensors 10, no. 7 (July 8, 2020): 75. http://dx.doi.org/10.3390/bios10070075.
Повний текст джерелаАнотація:
A self-powered biosensor for monitoring the maximal lactate steady state (MLSS) during exercise has been developed for intelligently assisting training system. It has been presented to create poly (vinylidene fluoride) (PVDF)/Tetrapod-shaped ZnO (T-ZnO)/enzyme-modified nanocomposite film through an efficient and cost-effective fabrication process. This sensor can be readily attached to the skin surface of the tester. Due to the piezoelectric surface coupling effect, this biosensor can monitor/sense and analyze physical information in real-time under the non-invasive condition and work independently without any battery. By actively outputting piezoelectric signals, it can quickly and sensitively detect body movements (changes of joint angle, frequency relative humidity during exercise) and physiological information (changes of lactate concentration in sweat). A practical application has been demonstrated by an excellent professional speed skater (male). The purpose of this study is to increase the efficiency of MLSS evaluation, promote the development of piezoelectric surface coupling effect and motion monitoring application, develop an intelligently assisting training system, which has opened up a new direction for human motion monitoring.
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Mahood, Hanaa E., and Baydaa M. Abbood. "Physiological and Histological Study of Preventive effect of Antioxidants, Selenium and Vitamin C with Garlic in Rats treated with Sodium Fluoride." Research Journal of Pharmacy and Technology 11, no. 3 (2018): 941. http://dx.doi.org/10.5958/0974-360x.2018.00174.9.
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PALAPARTI, Anuradha, Yuan LI, and Madhu B. ANAND-SRIVASTAVA. "Inhibition of atrial natriuretic peptide (ANP) C receptor expression by antisense oligodeoxynucleotides in A10 vascular smooth-muscle cells is associated with attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase." Biochemical Journal 346, no. 2 (February 22, 2000): 313–20. http://dx.doi.org/10.1042/bj3460313.
Повний текст джерелаАнотація:
Atrial natriuretic peptide (ANP) mediates a variety of physiological effects through its interaction with ANP-A, ANP-B or ANP-C receptors. However, controversies exist regarding the involvement of ANP-C receptor and adenylyl cyclase/cAMP signal-transduction systems to which these receptors are coupled in mediating these responses. In the present studies, we have employed an antisense approach to eliminate the ANP-C receptor and to examine the effect of this elimination on adenylyl cyclase inhibition. An 18-mer antisense phosphorothioate oligodeoxynucleotide (OH-2) targeted at the initiation codon of the ANP-C receptor was used to examine its effects on the expression of the ANP-C receptor and ANP-C-receptor-mediated inhibition of adenylyl cyclase in vascular smooth-muscle cells (A10). Treatment of the cells with antisense oligonucleotide resulted in complete attenuation of C-ANP4-23 [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANP4-23-NH2]-mediated inhibition of adenylyl cyclase, whereas sense and missense oligomers did not affect the inhibition of adenylyl cyclase by C-ANP4-23. In addition, the stimulatory effects of guanine nucleotides, isoproterenol, sodium fluoride and forskolin as well as the inhibitory effects of angiotensin II on adenylyl cyclase were not affected by antisense-oligonucleotide treatment. The attenuation of C-ANP4-23-mediated inhibition of adenylyl cyclase by antisense oligonucleotide was dose- and time-dependent. A complete attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase was observed at 2.5 μM. In addition, treatment of the cells with antisense oligonucleotide and not with sense or missense oligomers resulted in the inhibition of the levels of ANP-C-receptor protein and mRNA as determined by immunoblotting and Northern blotting using antisera against the ANP-C receptor and a cDNA probe of the ANP-C receptor respectively. On the other hand, ANP-A/B-receptor-mediated increases in cGMP levels were not inhibited by antisense-oligonucleotide treatment. Our results demonstrate conclusively that the elimination of ANP-C receptor by antisense oligonucleotide attenuates ANP-induced inhibition of adenylyl cyclase and provide evidence that antisense oligonucleotide of the ANP-C receptor may serve as a useful pharmacological tool to elucidate the physiological functions of the ANP-C receptor.
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Iozzo, Patricia, Panithaya Chareonthaitawee, Marco Di Terlizzi, D. John Betteridge, Ele Ferrannini, and Paolo G. Camici. "Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans." American Journal of Physiology-Endocrinology and Metabolism 282, no. 5 (May 1, 2002): E1163—E1171. http://dx.doi.org/10.1152/ajpendo.00386.2001.
Повний текст джерелаАнотація:
We investigated the effect of insulin on total and regional myocardial blood flow (MBF) and glucose uptake (MGU) in healthy subjects (50 ± 5 yr) by means of positron emission tomography (PET) with oxygen-15-labeled water (H2 15O) and fluorine-18 labeled fluorodeoxyglucose (18FDG) before and during physiological hyperinsulinemia (40 mU · min−1 · m−2). Twelve male subjects were included in the study. During hyperinsulinemia, MBF increased from 0.91 ± 0.28 to 1.01 ± 0.31 ml · min−1 · g−1 ( n= 7 patients, P = 0.05; n = 112 regions, P < 0.005). Intersubject variability ranged from −3.0 to +41%. MGU increased from 0.11 ± 0.08 ( n = 5) to 0.56 ± 0.08 μmol · min−1 · g−1( P < 0.0001, n = 7). MBF and insulin-mediated MGU were higher in the septum and anterior and lateral wall along short-axis regions of the heart. During hyperinsulinemia, MBF was also higher in the apex and midventricle compared with the base. MBF and MGU were positively correlated before ( r = 0.66, P < 0.0001) and during hyperinsulinemia ( r= 0.24, P < 0.05). These results provide evidence that insulin stimulates MBF in normal human hearts and appears to involve mainly those regions of the heart where insulin-mediated MGU is higher. Furthermore, regional distribution of insulin-stimulated MBF and MGU does not appear to be uniform across the left ventricular wall of healthy subjects.
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Ghantous, Hanan N., Jeanne Fernando, Scott E. Morgan, A. Jay Gandolfi, and Klaus Brandel. "Precision-cut Guinea-pig Liver Slices as a Tool for Studying the Toxicity of Volatile Anaesthetics." Alternatives to Laboratory Animals 18, no. 1_part_1 (November 1990): 191–99. http://dx.doi.org/10.1177/026119299001800120.1.
Повний текст джерелаАнотація:
Cultured precision-cut liver slices retain normal liver architecture and physiological biochemical functions. Hartley male guinea-pig liver slices have proven to be a good model for studying the biotransformation and toxicity of halothane. This system was used to evaluate the biotransformation and toxicity of different volatile anaesthetics (halothane, enflurane, isoflurane and sevoflurane), and compare their effects to those of new anaesthetics (desflurane). Liver slices (250–300μm thick) were incubated in sealed roller vials, containing Krebs Henseleit buffer at 37°C under 95% O2:5% CO2 atmosphere. Volatile anaesthetics were delivered by volatilisation after pre-incubation for 1 hour to produce a constant concentration in the medium. Production of the metabolites, trifluroacetic acid and fluoride ion, was measured. Intracellular potassium ion content, protein synthesis and secretion were determined as indicators of viability of the slices. The rank order of biotransformation of anaesthetics by the liver slices was halothane >sevoflurane>isoflurane and enflurane>desflurane. The rank order of hepatotoxicity of these anaesthetics was halothane>isoflurane and enflurane>sevoflurane and desflurane. Halothane is the anaesthetic which is metabolised furthest and has the most toxic effect, while desflurane is the least metabolised anaesthetic and has the least toxicity. This in vitro cultured precision-cut liver slice system appears to be suitable for studying the biotransformation of volatile anaesthetics and correlating its role in the resulting toxicity.
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Meyer-Fernandes, José Roberto, Mario Alberto da Silva-Neto, Mirna dos Santos Soares, Eloise Fernandes, Anibal Eugênio Vercesi, and Mécia Maria de Oliveira. "Ecto-Phosphatase Activities on the Cell Surface of the Amastigote Forms of Trypanosoma cruzi." Zeitschrift für Naturforschung C 54, no. 11 (November 1, 1999): 977–84. http://dx.doi.org/10.1515/znc-1999-1120.
Повний текст джерелаАнотація:
Abstract Live Trypanosoma cruzi amastigotes hydrolyzed p-nitrophenylphosphate (PNPP), phos-pho-amino-acids and 32P-casein under physiologically appropriate conditions. PNPP was hydrolysed at a rate of 80 nmol ·mg -1 ·h -1 in the presence of 5 mм MgCl2, pH 7.2 at 30 °C. In the absence of Mg2+ the activity was reduced 40% and we call this basal activity. At saturating concentration of PNPP, half-maximal PNPP hydrolysis was obtained with 0.22 mм MgCl2· Ca2+ had no effect on the basal activity, could not substitute Mg2+ as an activator and in contrast inhibited the PNPP hydrolysis stimulated by Mg2+ (I50 = 0.43 mм ) . In the absence of Mg2+ (basal activity) the stimulating half concentration (S0. 5) for PNPP was 1.57 mм , while at saturating MgCl2 concentrations the corresponding S0.5 for PNPP for Mg2+-stimulated phosphatase activity (difference between total minus basal phosphatase activity) was 0.99 mм . The Mg-dependent PNPP hydrolysis was strongly inhibited by sodium fluoride (NaF), vanadate and Zn2+ but not by tartrate and levamizole. The Mg-independent basal phosphatase activity was insensitive to tartrate, levamizole as well NaF and less inhibited by vanadate and Zn2+. Intact amastigotes were also able to hydrolyse phosphoserine, phos-phothreonine and phosphotyrosine but only the phosphotyrosine hydrolysis was stimulated by MgCl2 and inhibited by CaCl2 and phosphotyrosine was a competitive inhibitor of the PNPP hydrolysis stimulated by Mg2+. The cells were also able to hydrolyse 32P-casein phosphorylated on serine and threonine residues but only in the presence of MgCl2. These results indicate that in the amastigote form of T. cruzi there are at least two ectophosphatase activities, one of which is Mg2+ dependent and can dephosphorylate phospho-aminoacids and phosphoproteins under physiological conditions.
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Aldergham, Samar, Abdalmageed Qopori, Raad Bahmaishan, Wessam Tayyar, Sadaga Maghrabi, Rinad Nawab, Majd Eskndrani, and Yazeed Albudair. "Methods and Challenges in Preventive Dental Care of the Elderly." Journal of Healthcare Sciences 02, no. 11 (2022): 354–60. http://dx.doi.org/10.52533/johs.2022.21104.
Повний текст джерелаАнотація:
As individuals age, physiologic alterations take place in the oral cavity, and are thought to be a regular component of the ageing process. However, pathological developments that are not harmless, and that need professional care, are frequently encountered. The line between physiological ageing and actual pathological changes is not clear in all cases. The wellbeing of the oral cavity can be compromised with the initiation of tooth loss, soft tissue lesions such as oral carcinoma, neglected grossly carious teeth, neglected severe periodontitis, and orofacial neuralgia. For adequate oral health to be retained in older ages, oral diseases must be prevented and/or treated with emphasis in younger ages. Proper self-management measures—like brushing of teeth with a fluoridated toothpaste, dental flossing, and consuming nutrient-dense and balanced meals which have less refined carbohydrate are crucial preventive practices to be incorporated in daily life by people of all ages which includes the elderly. Dental care professionals can play a major role in prevention of dental problems and avoidance of more damage of oral tissues in older people. Professional activities comprise head, neck, and intraoral assessment of teeth and surrounding tissues for presence of oral manifestations of systemic illnesses, oral neoplasms, carious teeth, periodontitis, and impaired function and esthetics. Other measures for prevention comprise prophylaxis, dental care guidance, fluoride varnish provision, and proper therapy via restorations and reconstructions. Since the effects of dental conditions accrue as time passes, the necessity for sooner establishment of a preventive routine in life is vital for healthy ageing intraorally. Further, dental care for the geriatric population initiates in the younger ages through a stress on management of oral health issues early on, and from that point through an elaborate preventive plan moving ahead.
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Gandra, Rafael M., Laura N. Silva, Xênia M. Souto, Leandro S. Sangenito, Lucas P. S. Cruz, Lys A. Braga-Silva, Diego S. Gonçalves, Sergio H. Seabra, Marta H. Branquinha, and André L. S. Santos. "The serine peptidase inhibitor TPCK induces several morphophysiological changes in the opportunistic fungal pathogen Candida parapsilosis sensu stricto." Medical Mycology 57, no. 8 (February 9, 2019): 1024–37. http://dx.doi.org/10.1093/mmy/myz008.
Повний текст джерелаАнотація:
AbstractCandida parapsilosis sensu stricto (C. parapsilosis) has emerged as the second/third commonest Candida species isolated from hospitals worldwide. Candida spp. possess numerous virulence attributes, including peptidases that play multiple roles in both physiological and pathological events. So, fungal peptidases are valid targets for new drugs development. With this premise in mind, we have evaluated the effect of serine peptidase inhibitors (SPIs) on both cell biology and virulence aspects of C. parapsilosis. First, five different SPIs, phenylmethylsulfonyl fluoride, benzamidine, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, N-α-tosyl-L-lysine chloromethyl ketone hydrochloride, and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) were tested, and TPCK showed the best efficacy to arrest fungal growth. Subsequently, the ability of TPCK to modulate physiopathological processes was investigated. Overall, TPCK was able to (i) inhibit the cell-associated serine peptidase activities, (ii) promote morphometric and ultrastructural alterations, (iii) induce an increase in the intracellular oxidation level, which culminates in a vigorous lipid peroxidation and accumulation of neutral lipids in cytoplasmic inclusions, (iv) modulate the expression/exposition of surface structures, such as mannose/glucose-rich glycoconjugates, N-acetylglucosamine-containing molecules, chitin, polypeptides and surface aspartic peptidases, (v) reduce the adhesion to either polystyrene or glass surfaces as well as to partially disarticulate the mature biofilm, (vi) block the fungal interaction with macrophages, and (vii) protect Galleria mellonella from fungal infection, enhancing larvae survivability. Altogether, these results demonstrated that TPCK induced several changes over fungal biology besides the interference with aspects associated to C. parapsilosis virulence and pathogenesis, which indicates that SPIs could be novel promising therapeutic agents in dealing with candidiasis.
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Million, D., P. Zillner, and R. Baumann. "Oxygen pressure-dependent control of carbonic anhydrase synthesis in chick embryonic erythrocytes." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 5 (November 1, 1991): R1188—R1196. http://dx.doi.org/10.1152/ajpregu.1991.261.5.r1188.
Повний текст джерелаАнотація:
During chick embryonic development carbonic anhydrase (CA) expression of erythrocytes is kept at a very low level until the last week of incubation (i.e., up to day 14). We have previously obtained evidence that hypoxia is the physiological stimulus for rapid onset of CA synthesis before hatching. Looking for putative signals we have carried out in vitro incubations of embryonic erythrocytes, screening a large number of hormones and second messengers, which were all ineffective, with the exception of the A1 agonist N6-phenylisopropyladenosine (adenosine had no effect). However, incubation with embryonic plasma (10%) from embryos greater than 6 days caused a 10-fold increase of the CA activity during 24 h. This increase was not observed when the incubation was carried out with the addition of actinomycin D, cycloheximide, aluminum fluoride, pertussis toxin, or heat-inactivated plasma. Mammalian plasma had no effect on CA activity. Filtration experiments show that the molecular mass of the factor is less than 2,000 Da. We conclude that embryonic plasma contains a heat-labile factor which stimulates CA synthesis via activation of transcription and whose receptor is coupled to a pertussis toxin-sensitive G protein. In vivo the action of the plasma factor is suppressed as long as blood Po2 is high, suggesting the presence of an inhibitor molecule whose synthesis is controlled by the Po2.
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Wang, Xu. "A Multifunctional Flexible Ferroelectric Transistor Sensor Based on Si/Fe-Doped Indium Oxide for Electronic Skin." Journal of Nanomaterials 2022 (August 16, 2022): 1–7. http://dx.doi.org/10.1155/2022/2952589.
Повний текст джерелаАнотація:
As the sensing basis and data source of the new generation of information technology, sensors play a vital role in today’s information age. The purpose of this work is to construct a flexible ferroelectric field-effect transistor (FeFET) as a prototype for a multifunctional sensor for electronic skin. The FeFET device is fabricated from poly(vinylidene fluoride-dimethylsiloxane) (P(VDF-DMS)) and Si/Fe-doped indium oxide (SFIO). Furthermore, this device is capable of three-in-one sensing. Specifically, it can detect temperature changes from 0°C to 70°C and monitors external forces with a linear sensitivity of 4.6 nA·kPa-1 across a pressure range of 50 kPa to 150 kPa. Additionally, electrostatic interaction enables the gadget to detect the approach of a charged item. Furthermore, this gadget was built to detect physiological signals produced by the human body, such as pulse, respiration, and finger movements. It is very bend-resistant and retains transmission properties after 1200 cycles of bending. Moreover, we will examine the device’s sensitivity to temperature variations and charged particles when bent to a radius of 1.09 mm. This design will promote the next generation multifunctional E-skin.
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SVISTUNENKO, Dimitri A., Martyn A. SHARPE, Peter NICHOLLS, Christine BLENKINSOP, Nathan A. DAVIES, Jacqueline DUNNE, Michael T. WILSON, and Chris E. COOPER. "The pH dependence of naturally occurring low-spin forms of methaemoglobin and metmyoglobin: an EPR study." Biochemical Journal 351, no. 3 (October 24, 2000): 595–605. http://dx.doi.org/10.1042/bj3510595.
Повний текст джерелаАнотація:
The paramagnetic species in human metHb and horse metmyoglobin (metMb) have been studied at low temperature using EPR spectroscopy. The high-spin (HS) haem signal in aquometMb has a greater rhombic distortion than the HS metHb signal. Nevertheless, the individual line width (g = 6) is smaller in metMb than in metHb, consistent with non-identical signals from the α and β Hb subunits. Three low-spin (LS) haem forms are present in metHb, while metMb has only two. The major LS form in both proteins is the alkaline species (with OH- at the sixth co-ordination position). The minor LS forms are assigned to different histidine hemichromes in equilibrium with the normal HS species at low temperature. LS forms disappear when the haem is bound by a ligand, such as fluoride, which ensures 100% occupancy of the HS state both at room temperature and at 25K. The small differences in effective g-factors of the histidine hemichromes are interpreted in terms of different distances between the distal histidine and haem iron. The pH dependence of the inter-conversion of the different paramagnetic species is consistent with a model whereby protonation of a residue with a pK of 5.69 (metHb) or 6.12 (metMb), affects ligand binding and transformation from the HS to the LS form. Chemical and spectroscopic considerations suggest that the residue is unlikely to be the proximal or distal histidine. We therefore propose a model where protonation of this distant amino acid causes a conformational change at the iron site. Identical effects are seen in frozen human blood, suggesting that this effect may have physiological significance.
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Abdelrahman, Mutassim M., Ibrahim A. Alhidary, Riyadh S. Aljumaah, and Bernard Faye. "Blood Trace Element Status in Camels: A Review." Animals 12, no. 16 (August 18, 2022): 2116. http://dx.doi.org/10.3390/ani12162116.
Повний текст джерелаАнотація:
Trace minerals play an important role in animal health and productivity. They are involved also in many physiological activities, and their deficiency causes a variety of pathological problems and metabolic defects, reducing consequently the animal productivity. The demand for animal products in semi-arid areas is rapidly increasing, and the supply is still below the required level, partially due to low animal productivity. Camels (Camelus dromedarius and Camelus bactrianus) are considered one of the main sources of healthy, high-quality meat and milk for human consumption within most of the countries in the semi-arid regions. Despite their efficient adaptation to their environment, camels can suffer from the growth retardation of newborns, low feed efficiency, anemia, poor fertility, poor reproduction and many other metabolic disorders. It is well known that trace mineral deficiencies and trace mineral toxicities can influence camels’ production and reproductive efficiency, as well as many aspects of their growth and metabolism. Evaluating the trace minerals status of camels and their variability is an obvious step toward improving camels’ productivity and health. Thus, the present article reviews the data regarding the status of trace minerals (copper, zinc, iron, selenium, manganese, cobalt, iodine, fluorine, molybdenum, sulfur, bromide and nickel) in camel blood and their physiological variability, with a focus on their deficiency and toxicity effects.
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DiCorleto, P. E., and C. A. de la Motte. "Thrombin causes increased monocytic-cell adhesion to endothelial cells through a protein kinase C-dependent pathway." Biochemical Journal 264, no. 1 (November 15, 1989): 71–77. http://dx.doi.org/10.1042/bj2640071.
Повний текст джерелаАнотація:
The coagulation protein thrombin has been shown to stimulate multiple endothelial-cell (EC) functions, including production of platelet-derived growth factor and of platelet-activating factor (PAF), and neutrophil adhesion. We have found that thrombin causes increased binding of monocytic cells (U937 cells and normal human monocytes) to cultured EC of various species. Maximum adhesion of monocytes to pig aortic EC occurred 6 h after thrombin treatment and remained elevated through 24 h. Stimulation of adherence by bovine alpha-thrombin was half-maximal at 15 units/ml, and reached a plateau at 50 units/ml. Catalytically inactive thrombin (phenylmethanesulphonyl fluoride-treated) had no effect on monocyte adhesion to EC. Heparin, but not the endotoxin antagonist polymyxin B, suppressed the stimulation of adhesion by thrombin without altering basal adhesion. Two lines of evidence suggested that protein kinase C (PKC) was involved in the intracellular signalling to increase monocyte adhesion to EC. First the PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated monocytic-cell adhesion to EC at a dose consistent with stimulation of PKC (half-maximal response at 1-3 nM) and with a time course similar to that for thrombin stimulation (maximal by 4 h). Diacylglycerol, a physiological activator of PKC, also stimulated U937-cell adhesion to EC. Secondly, H7, a PKC inhibitor, completely blocked stimulation of monocyte adhesion to EC by thrombin or PMA. The structural analogue of H7, HA1004, which preferentially inhibits cyclic-AMP- and cyclic-GMP-dependent protein kinases, had no effect on stimulated monocyte adhesion. The PKC inhibitor also blocked the stimulation of monocyte adhesion to EC by interleukin-1 and endotoxin, but did not alter the basal level of monocyte binding to unstimulated EC. Thrombin stimulation of monocyte adhesion differed from the reported stimulation of neutrophil adhesion by thrombin in that the latter process reached a maximum in minutes rather than hours. In addition, neither PAF itself nor agents known to stimulate PAF production by EC, such as arachidonate and the Ca2+ ionophore A23187, had any effect on monocyte adhesion. These results demonstrate a PKC-dependent cytokine-like action of the coagulation protein thrombin in modulating monocytic-cell adhesion to EC, a phenomenon of potential importance in many pathological and physiological processes.
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He, L., B. Dinger, K. Sanders, J. Hoidal, A. Obeso, L. Stensaas, S. Fidone, and C. Gonzalez. "Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 289, no. 6 (December 2005): L916—L924. http://dx.doi.org/10.1152/ajplung.00015.2005.
Повний текст джерелаАнотація:
Membrane potential in oxygen-sensitive type I cells in carotid body is controlled by diverse sets of voltage-dependent and -independent K+ channels. Coupling of Po2 to the open-closed state of channels may involve production of reactive oxygen species (ROS) by NADPH oxidase. One hypothesis suggests that ROS are produced in proportion to the prevailing Po2 and a subset of K+ channels closes as ROS levels decrease. We evaluated ROS levels in normal and p47 phox gene-deleted [NADPH oxidase knockout (KO)] type I cells using the ROS-sensitive dye dihydroethidium (DHE). In normal cells, hypoxia elicited an increase in ROS, which was blocked by the specific NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF, 3 mM). KO type I cells did not respond to hypoxia, but the mitochondrial uncoupler azide (5 μM) elicited increased fluorescence in both normal and KO cells. Hypoxia had no effect on ROS production in sensory and sympathetic neurons. Methodological control experiments showed that stimulation of neutrophils with a cocktail containing the chemotactic peptide N-formyl-Met-Leu-Phe (1 μM), arachidonic acid (10 μM), and cytochalasin B (5 μg/ml) elicited a rapid increase in DHE fluorescence. This response was blocked by the NADPH oxidase inhibitor diphenyleneiodonium (10 μM). KO neutrophils did not respond; however, azide (5 μM) elicited a rapid increase in fluorescence. Physiological studies in type I cells demonstrated that hypoxia evoked an enhanced depression of K+ current and increased intracellular Ca2+ levels in KO vs. normal cells. Moreover, AEBSF potentiated hypoxia-induced increases in intracellular Ca2+ and enhanced the depression of K+ current in low O2. Our findings suggest that local compartmental increases in oxidase activity and ROS production inhibit the activity of type I cells by facilitating K+ channel activity in hypoxia.
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Rhodes, CG, and JM Hughes. "Pulmonary studies using positron emission tomography." European Respiratory Journal 8, no. 6 (June 1, 1995): 1001–17. http://dx.doi.org/10.1183/09031936.95.08061001.
Повний текст джерелаАнотація:
The detailed investigation of regional differences in lung function at a local level began when suitable gamma-ray emitting isotopes and focused external radiation detectors (especially the Anger gamma-camera) became available. A major recent advance has been the development of positron emission tomography (PET), which provides a powerful combination of highly accurate tomographic reconstruction of radioisotope concentration with a potentially unlimited list of biological compounds to be labelled with the positron emitting isotopes of oxygen, carbon and fluorine. Early studies using PET focused on the inhalation of 11CO (or C15O) and 19Ne gases and the intravenous injection of 13N in saline and H215O for the measurement of relatively simple aspects of regional lung function, such as tissue, blood and gas volumes, blood flow, ventilation and ventilation/perfusion (V'A/Q'). More recent work has been directed towards the more challenging areas of regional endothelial permeability, carbohydrate utilization, enzyme and receptor binding assays, and in vivo pharmacokinetics. The short physical half-lives of the isotopes (17 s to 2 h) and the noninvasive nature of PET allows serial measurements to be made on patients (within the constraints of permitted radiation doses) to assess the effect of physiological and therapeutic interventions.
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Furman R.L.*, Barylo O. S. ,. Agafonov K. V. ,. Kirichek O. V. ,. "COMPREHENSIVE STUDY OF ORAL HYGIENE STATUS IN 40-50 YEAR-OLD WOMEN RANGES USING DRUG PRODUCT TO INCREASE RESISTANCE OF DENTAL HARD TISSUES." Innovative Journal of Medical and Health Science 9, no. 3 (March 22, 2019): 343–46. http://dx.doi.org/10.15520/ijmhs.v9i3.2483.
Повний текст джерелаАнотація:
Resistance of tooth enamel to aggressive effect of metabolic by-products of oral cavity microorganisms is provided by fluoroapatites of enamel surface layers. The patients were divided into two groups: control group (30 females) and experimental (observa-tion) group (30 females). In control group, the traditional method of caries prevention was used, which included professional teeth cleaning, mouthwash with physiological solution (0.9%) of sodium chloride after meals, hygienic teeth brushing by a standard method twice a day. Females of experimental group underwent professional teeth cleaning, treatment of teeth with the drug product containing sodium fluoride to in-crease the resistance of hard tissues of teeth, silver nitrate and decamethoxin, rinsing with standardized decamethoxin solution. Various indices are used in modern den-tistry to evaluate oral hygiene status. Index estimation provides quantitative charac-teristics of static status of oral hygiene. Their values enable to suggest the course of inflammatory-destructive or dystrophic process and its severity, to evaluate treatment efficacy and quality of regular check-up of a particular patient or dispensary cases. The study demonstrated significant positive clinical efficacy of the drug product used to increase resistance of dental hard tissues. In particular, patients using the pharma-ceutical preparation to improve the resistance of dental hard tissues, had significantly lower values of Fedorov-Volodkina’s Index, Greene-Vermillion Index (Oral Hygiene Index- Simplified), Patient Hygiene Performance (PHP) Index as compared to the control group.
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Isaac, R. E. "Proctolin degradation by membrane peptidases from nervous tissues of the desert locust (Schistocerca gregaria)." Biochemical Journal 245, no. 2 (July 15, 1987): 365–70. http://dx.doi.org/10.1042/bj2450365.
Повний текст джерелаАнотація:
The hydrolysis of the insect neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) by enzyme preparations from the nervous tissue of the desert locust (Schistocerca gregaria) was investigated. Neural homogenate degraded proctolin (100 microM) at neutral pH by cleavage of the Arg-Tyr and Tyr-Leu bonds to yield Tyr-Leu-Pro-Thr, Arg-Tyr and free tyrosine. Arg-Tyr was detected as a major metabolite when the aminopeptidase inhibitors amastatin and bestatin were present to prevent Arg-Tyr breakdown. Around 50% of the proctolin-degrading activity was isolated in a 30,000 g membrane fraction and was shown to be almost entirely due to aminopeptidase activity. The aminopeptidase had an apparent Km of 23 microM, a pH optimum of 7.0 and was inhibited by 1 mM-EDTA and amastatin [IC50 = 0.3 microM], but was relatively insensitive to bestatin, actinonin and puromycin. Phenylmethanesulphonyl fluoride (1 mM) and p-chloromercuriphenylsulphonic acid (1 mM) had no effect on this enzyme activity. Although the bulk of the Tyr-Leu hydrolytic activity was located in the 30,000 g supernatant, some weak activity was detected in a washed membrane preparation. This peptidase displayed a high affinity for proctolin (Km = 0.35 microM) and optimal activity at around pH 7.0. Synaptosome- and mitochondria-rich fractions were prepared from crude neural membranes. The aminopeptidase activity was concentrated in the synaptic-membrane preparation, whereas activity giving rise to Arg-Tyr was predominantly localized in the mitochondrial fraction. The subcellular localization of the membrane aminopeptidase is consistent with a possible physiological role for this enzyme in the inactivation of synaptically released proctolin.
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Kumar, Dhiraj, Akhilesh Mishra, Ala Lisok, Rakeeb Kureshi, Sagar Shelake, Donika Plyku, Rupashree Sen, et al. "Pharmacodynamic measures within tumors expose differential activity of PD(L)-1 antibody therapeutics." Proceedings of the National Academy of Sciences 118, no. 37 (September 10, 2021): e2107982118. http://dx.doi.org/10.1073/pnas.2107982118.
Повний текст джерелаАнотація:
Macromolecules such as monoclonal antibodies (mAbs) are likely to experience poor tumor penetration because of their large size, and thus low drug exposure of target cells within a tumor could contribute to suboptimal responses. Given the challenge of inadequate quantitative tools to assess mAb activity within tumors, we hypothesized that measurement of accessible target levels in tumors could elucidate the pharmacologic activity of a mAb and could be used to compare the activity of different mAbs. Using positron emission tomography (PET), we measured the pharmacodynamics of immune checkpoint protein programmed-death ligand 1 (PD-L1) to evaluate pharmacologic effects of mAbs targeting PD-L1 and its receptor programmed cell death protein 1 (PD-1). For PD-L1 quantification, we first developed a small peptide-based fluorine-18–labeled PET imaging agent, [18F]DK222, which provided high-contrast images in preclinical models. We then quantified accessible PD-L1 levels in the tumor bed during treatment with anti–PD-1 and anti–PD-L1 mAbs. Applying mixed-effects models to these data, we found subtle differences in the pharmacodynamic effects of two anti–PD-1 mAbs (nivolumab and pembrolizumab). In contrast, we observed starkly divergent target engagement with anti–PD-L1 mAbs (atezolizumab, avelumab, and durvalumab) that were administered at equivalent doses, correlating with differential effects on tumor growth. Thus, we show that measuring PD-L1 pharmacodynamics informs mechanistic understanding of therapeutic mAbs targeting PD-L1 and PD-1. These findings demonstrate the value of quantifying target pharmacodynamics to elucidate the pharmacologic activity of mAbs, independent of mAb biophysical properties and inclusive of all physiological variables, which are highly heterogeneous within and across tumors and patients.