Redistribution Of Calcium Research Articles

Dynamics of changes in cadmium levels in environmental objects and its impact on the bio-elemental composition of living organisms.

As a result of intensive anthropogenic impact in the biosphere there is a rapid process of accumulation of heavy metal salts. They have led to the aggravation of problems associated with the pollution of ecosystems and basic food products of plant and animal origin. Environmental pollution by these compounds is caused by their persistence in environmental objects, migration ability, accumulation by plants. This contributes to their accumulation in the human environment. A number of studies have shown that heavy metals have mutagenic, toxic effects and affect the intensity of biochemical processes. Therefore, the presence of heavy metals in the environment is extremely undesirable. Moreover, the ecological state of the environment is directly related to changes in the human internal environment. Deficiency or excess of certain bioelements in soils and drinking water or non-compliance with its stable chemical composition causes the development of dysmicroelementosis. The ecological situation of the Carpathian region is closely related to the state of soils and water resources. In this regard, it is advisable to study and control the level of cadmium compounds in the environment of the region. The study of the effect of cadmium intoxication on the macro- and microelement composition of the brain and myocardium of experimental animals is also worthwhile. Materials and methods. Soils and drinking water of the plain, foothill and mountainous zones of the region, as well as organs and tissues of experimental animals served as the object of research. Cadmium levels in drinking water and myocardial tissues and brain of experimental animals have been measured by atomic absorption spectroscopy. Results and discussion. The study of soils in the Prykarpattia region has revealed an increase in the toxic element cadmium. Its content is 1.1-1.5 times higher than background levels. The analysis of drinking water allowed to establish that a significant number of people living in the plain and foothill zone of the region consume water with a high content of cadmium. The main stages of cadmium intake and accumulation in plants have been analyzed. Significant disorders in the body of experimental animals under conditions of excessive intake of cadmium compounds have been revealed. It was accompanied by the accumulation of cadmium in the myocardium and brain, on the background of redistribution of vital macronutrients calcium and magnesium along with micronutrients copper and zinc. Thus, excessive intake of cadmium salts causes the development of dysmicroelementosis, which is accompanied by a violation of the homeostasis of a living organism. It is suggested to conduct continuous monitoring of the level of toxicants in the ecosystem as an integral component of environmental monitoring.

Mal'javr – the first gold prospect in the Archean conglomerates, the Kola region

A new type of prospects of gold mineralization in the Kola region is considered in the paper. The Mal'javr prospect is located in the south-western flank of the Uragubsky greenstone belt in biotite gneiss – the metamorphosed sedimentary rocks with interlayering of polymictic conglomerate, gravelite, and sandstone. Gold-bearing sulfide mineralization was found in altered rocks, which form a series of lens-shaped bodies, concentrated along a shear zone of NNE strike. The bodies of altered rocks are zonal: the central zone makes 50–80 % of the lens volume, it consists of garnet and quartz, the intermediate zone is of garnet-biotite mineral composition, and in the outer zone, which is often reduced, the main minerals are hedenbergite, hornblende, and grunerite. The metasomatic alteration is connected with an increase of iron content, decrease of Al, Si, and alkaline metals Na and K, redistribution of calcium to the outer zone of metasomatic lenses; and magnesium is inert. If compared to the unaltered gneiss, the altered rocks are depleted in Rb, Cs, Sr, Ba, Zr, Nb; and content of Cu, Zn, Mn, As, Ag, Te, W, Bi (all these elements are known to associate with gold) increases. All zones of altered rocks are rich in sulfide mineralization. Pyrrhotite and arsenopyrite are the main sulfide minerals, minor minerals are chalcopyrite, pentlandite, magnetite, tochilinite, native gold, and late pyrite and marcasite. Rock alteration and formation of sulfide mineralization happened at a high temperature > 600 °С, and the late alteration processes at ~400 °C. The arsenopyrite-gold mineralization probably formed with As and Au mobilized from the host biotite gneiss during regional metamorphism or due to pegmatite vein intrusion.

A Fatal Case of Metastatic Pulmonary Calcification during the Puerperium

We present an unusual case of a fatal respiratory failure in a young woman developed two weeks after she gave birth at home. Circumstantial and clinical features of the case were strongly suggestive for a 'classical' septic origin of the respiratory symptoms. Autopsy, together with histopathological and immunohistochemical analyses allowed demonstrating a massive calcium redistribution consisting of an important osteolysis, especially from cranial bones and abnormal accumulation in lungs and other organs. Such physiopathology was driven by a primary hyperparathyroidism secondary to a parathyroid carcinoma as demonstrated by immunohistochemistry. This very rare case is furthermore characterised by a regular pregnancy course, ended with the birth of a healthy new-born. A complex interaction between pregnancy physiology and hyperparathyroidism might be hypothesised, determining the discrepancy between the relative long period of wellness and the tumultuous cascade occurred in the puerperium.

Influences of subcellular Ca redistribution induced by γ irradiation on the fruit firmness of refrigerated blueberries

To investigate influences of intracellular calcium (Ca) redistribution induced by irradiation treatments on the firmness of refrigerated blueberries, 'Bluecrop' blueberry fruit were irradiated with gamma (γ) ray at doses of 0.5, 1.0, and 2.5 kGy and unirradiated fruit served as the control (CK). The influences of different irradiation doses on changes in intracellular Ca2+ fluorescence signals and subcellular Ca distribution were evaluated, as well as correlations of these changes with the firmness of refrigerated blueberry fruit. Results showed that irradiation treatment could induce blueberry pulp cells to produce Ca2+ fluorescence signals and increase the intracellular Ca2+ concentration. In addition, the greater the dose during irradiation, the more significant its effect. In the refrigeration period, the intracellular Ca distribution had no effect on fruit firmness of blueberries irradiated at 0.5 kGy. Whereas, irradiated at 1.0 and 2.5 kGy could make Ca content increase in cell walls and decrease in organelle and cytoplasm, thus promoting Ca accumulation in cell wall at early stage of storage. Subcellular Ca redistribution induced by irradiation at 1.0 kGy was not related to the fruit firmness of refrigerated blueberries, but irradiation at 2.5 kGy could promote the migration of intracellular Ca to cell wall, which exerted a positive effect on the fruit firmness of refrigerated blueberries.

The Risk of the Development and Relationship of Kidney Stone Disease and Osteoporosis (Literature review)

Urinary stone disease (USD) is a common pathology with the formation of calculi in the kidneys, ureter, and bladder. Besides the family history, hyperparathyroidism, hypo- and hypervitaminosis of vitamin D, hypercalciuria, and hyperoxaluria are the high risk factors for USD development. This is due primarily to the activation of bone resorption with increased hypercalciuria. It is known that in the urine of every person there is a small amount of urea, inorganic salts, uric acid, creatinine and other substances. The main reason for the formation of calculi is a certain metabolic disorder, which leads to the formation of insoluble salts from which stones are formed – urates, phosphates, oxalates, etc. One of the unsolved problems in the metaphylaxis of USD is the treatment and prevention of osteoporosis which is comorbid with it, since calcium and vitamin D preparations are widely used for the prevention and treatment of osteoporosis. Osteoporosis and arterial calcification often coincide in the nature of the manifestation, which indicates an imbalance in the redistribution of calcium with a predominant direction in the vascular the wall. Vitamin K2 deficiency is closely related to the process of vascular calcification. In the cardiovascular system, with the use of vitamin K antagonists or vitamin K deficiency, calcification of the endothelium of blood vessels occurs. The effect of osteocalcin protein on stone formation processes is controversial. For example, some researchers have found that high serum level of Glaprotein is associated with a lower risk of kidney stones. Based on the results of a daily urinalysis study, the EAU Guidelines (2022) updated the recommendations on metaphylactic USD regarding the benefit/harm of additional calcium and vitamin D use in patients with nephrolithiasis depending on the type of crystalluria. The absence of recommendations for the management of patients with combined pathologies (USD, osteoporosis, cardiovascular diseases) prompts a comprehensive assessment of common risk factors, as well as the formation of programs and algorithms for early diagnosis and the development of recommendations for the prevention and avoidance of complications. Based on the literature analysis, it was established that today the issue of choosing the optimal management for diagnosis and treatment of USD and osteoporosis is still very controversial and ambiguous. There is a necessity for detailed study of this problem, the development of a complex differentiated approach to diagnosis and treatment of patients.

Molybdenum and cadmium co-exposure induces CaMKKβ/AMPK/mTOR pathway mediated-autophagy by subcellular calcium redistribution in duck renal tubular epithelial cells

Excessive molybdenum (Mo) and cadmium (Cd) are toxic environmental pollutants. Our previous research confirmed excessive Mo and Cd co-induced calcium homeostasis disorder and autophagy in duck kidneys, but how calcium ion (Ca2+) regulates autophagy is unclear. The results revealed that the Mo- and/or Cd-induced cytosolic Ca2+ concentration ([Ca2+]c) increase mainly came from intracellular calcium stores. Mo and/or Cd caused mitochondrial Ca2+ content ([Ca2+]mit) and [Ca2+]c increase with endoplasmic reticulum (ER) Ca2+ content ([Ca2+]ER) decrease and upregulated calcium homeostasis-related factor expression levels, but 2-Aminoethoxydiphenyl borate (2-APB) reversed subcellular Ca2+ redistribution. Increased Phospholipase C (PLC) and inositol 1,4,5-trisphosphate (IP3) activities and inositol 1,4,5-trisphosphate receptor (IP3R) expression level were observed in Mo- and/or Cd-treated cells, which was reversed by the PLC inhibitor U-73122. 2-APB and 1,2-Bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM) addition mitigated [Ca2+]c and autophagy (variations in microtubule-associated protein light chain 3 (LC3), LC3B-II/LC3B-I, autophagy related 5 (ATG5), sequestosome-1(P62), programmed cell death-1 (Beclin-1) and Dynein expression levels, LC3 puncta, autophagosomes and acid vesicle organelles) under Mo and/or Cd treatment, respectively, while thapsigargin (TG) had the opposite impacts. Additionally, the calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor STO-609 reversed the increased CaMKKβ, adenosine 5′-monophosphate-activated protein kinase (AMPK), Beclin-1, and LC3B-II/LC3B-I protein expression levels and reduced mammalian target of rapamycin (mTOR) and P62 protein expression levels in Mo- and/or Cd-exposed cells. Collectively, the results confirmed that [Ca2+]c overload resulted from PLC/IP3/IP3R pathway-mediated ER Ca2+ release, and then activated autophagy by the CaMKKβ/AMPK/mTOR pathway in Mo- and/or Cd-treated duck renal tubular epithelial cells.

High-Content Phenotypic Screen of a Focused TCAMS Drug Library Identifies Novel Disruptors of the Malaria Parasite Calcium Dynamics.

The search for new antimalarial drugs with unexplored mechanisms of action is currently one of the main objectives to combat the resistance already in the clinic. New drugs should target specific mechanisms that once initiated lead inevitably to the parasite's death and clearance and cause minimal toxicity to the host. One such new mode of action recently characterized is to target the parasite's calcium dynamics. Disruption of the calcium homeostasis is associated with compromised digestive vacuole membrane integrity and release of its contents, leading to programmed cell death-like features characterized by loss of mitochondrial membrane potential and DNA degradation. Intriguingly, chloroquine (CQ)-treated parasites were previously reported to exhibit such cellular features. Using a high-throughput phenotypic screen, we identified 158 physiological disruptors (hits) of parasite calcium distribution from a small subset of approximately 3000 compounds selected from the GSK TCAMS (Tres Cantos Anti-Malarial Set) compound library. These compounds were then extensively profiled for biological activity against various CQ- and artemisinin-resistant Plasmodium falciparum strains and stages. The hits were also examined for cytotoxicity, speed of antimalarial activity, and their possible inhibitory effects on heme crystallization. Overall, we identified three compounds, TCMDC-136230, -125431, and -125457, which were potent in inducing calcium redistribution but minimally inhibited heme crystallization. Molecular superimposition of the molecules by computational methods identified a common pharmacophore, with the best fit assigned to TCMDC-125457. There were low cytotoxicity or CQ cross-resistance issues for these three compounds. IC50 values of these three compounds were in the low micromolar range. In addition, TCMDC-125457 demonstrated high efficacy when pulsed in a single-dose combination with artesunate against tightly synchronized artemisinin-resistant ring-stage parasites. These results should add new drug options to the current armament of antimalarial drugs as well as provide promising starting points for development of drugs with non-classical modes of action.

Sub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome.

Direct injury of mitochondrial respiratory chain (RC) complex I by Ndufs4 subunit mutations results in complex I deficiency (CID) and a progressive encephalomyopathy, known as Leigh syndrome. While mitochondrial, cytosolic and multi-organelle pathways are known to be involved in the neuromuscular LS pathogenesis, compartment-specific metabolomics has, to date, not been applied to murine models of CID. We thus hypothesized that sub-cellular metabolomics would be able to contribute organelle-specific insights to known Ndufs4 metabolic perturbations. To that end, whole brains and skeletal muscle from late-stage Ndufs4 mice and age/sex-matched controls were harvested for mitochondrial and cytosolic isolation. Untargeted 1H-NMR and semi-targeted LC-MS/MS metabolomics was applied to the resulting cell fractions, whereafter important variables (VIPs) were selected by univariate statistics. A predominant increase in multiple targeted amino acids was observed in whole-brain samples, with a more prominent effect at the mitochondrial level. Similar pathways were implicated in the muscle tissue, showing a greater depletion of core metabolites with a compartment-specific distribution, however. The altered metabolites expectedly implicate altered redox homeostasis, alternate RC fueling, one-carbon metabolism, urea cycling and dysregulated proteostasis to different degrees in the analyzed tissues. A first application of EDTA-chelated magnesium and calcium measurement by NMR also revealed tissue- and compartment-specific alterations, implicating stress response-related calcium redistribution between neural cell compartments, as well as whole-cell muscle magnesium depletion. Altogether, these results confirm the ability of compartment-specific metabolomics to capture known alterations related to Ndufs4 KO and CID while proving its worth in elucidating metabolic compartmentalization in said pathways that went undetected in the diluted whole-cell samples previously studied.

Redistribution of calcium and sodium in calcareous soil profile and their effects on copper and lead uptake: A poplar-based phytomanagement

Poplar serves as a phytostabilizator in phytomanagement of the trace metals (TMs) copper (Cu) and lead (Pb) contaminated land. In the process of long-term phytomanagement, it is not clear how the cycling of the mineral nutrients calcium (Ca) and sodium (Na) in calcareous soil will affect poplar remediation mechanisms. We selected a site contaminated by Cu and Pb and phytomanaged by Populus simonii Carr. stands of different ages (7, 14, and 28 years) to study the influencing mechanisms. The results showed that after afforestation, the Ca in the subsoil returned to the topsoil through fallen leaves, whereas the Na in the topsoil migrated downward to the subsoil by leaching, resulting in the redistribution of mineral nutrients in the soil profile. In addition, the Ca content in soil solution of the root-zone was significantly lower relative to that of the bulk soil, whereas the Na content in soil solution was significantly higher in all stands. As a result, because of the competitive adsorption of mineral nutrient and TM cations on the soil surface, the pool of bioavailable TM in root-zone soils did not significantly decrease with stand age. On the contrary, the TM content in poplar leaves (Cu: 31–37 mg kg−1; Pb: 62–84 mg kg−1) and litter (Cu: 230–790 mg kg−1; Pb: 394–1366 mg kg−1) increased significantly with stand age. Nevertheless, the TM content in poplar wood (Cu < 3 mg kg−1; Pb < 12 mg kg−1) remained at an extremely low level in all stands. Our results highlighted that strengthening leaf collection is necessary to eliminate ecological risks and ensure the safe production of poplar wood in the long-term phytomanagement of TM-contaminated land.

Synchrotron µXRF imaging of live seedlings of Berkheya coddii and Odontarrhena muralis during germination and seedling growth

Nickel hyperaccumulator plants require highly evolved mechanisms to avoid cellular-level toxicity to cope with the high prevailing concentrations of nickel in their seeds and seedlings. This study aimed to investigate tissue-level distribution and redistribution of Ni and other physiologically relevant elements during the germination of hyperaccumulator plants. Berkheya coddii Roessler (Asteraceae) and Odontarrhena muralis sensu latu (Waldst. & Kit.) Endl. (O. chalcidica), formerly Alyssum murale (Waldst. & Kit.) (Brassicaceae), were germinated for several days at room temperature before using synchrotron micro X-ray Fluorescence Spectroscopy (µXRF) to obtain high-sensitivity and high-resolution elemental images of live/hydrated plants at various stages of seed germination and seedling growth. The results show that fruits and seeds of both species were highly enriched in nickel. In Berkheya coddii, nickel was located in the cotyledons, the micropylar area, the seed coat, and the point of attachment of the pappus with the cypsela body. In Odontarrhena muralis seeds, nickel occurred in the cotyledons and hypocotyl. The emergence of true leaves initiates nickel and calcium redistribution within seedlings in both species. The diversity in physiological responses to nickel in Berkheya coddii and Odontarrhena muralis does not only occur at the mature stage, but is inherent to both species as seed elemental storage and tolerance mechanisms during seedling development differ.

Calcium redistribution contributes to the hard-to-cook phenotype and increases PHA-L lectin thermal stability in common bean low phytic acid 1 mutant seeds

Seed phytic acid reduces mineral bioavailability by chelating minerals. Consumption of common bean seeds with the low phytic acid 1 (lpa1) mutation improved iron status in human trials but caused adverse gastrointestinal effects, presumably due to increased stability of lectin phytohemagglutinin L (PHA-L) compared to the wild type (wt). A hard-to-cook (HTC) defect observed in lpa1 seeds intensified this problem. We quantified the HTC phenotype of lpa1 common beans with three genetic backgrounds. The HTC phenotype in the lpa1 black bean line correlated with the redistribution of calcium particularly in the cell walls, providing support for the “phytase-phytate-pectin” theory of the HTC mechanism. Furthermore, the excess of free cations in the lpa1 mutation in combination with different PHA alleles affected the stability of PHA-L lectin.

Clemastine Fumarate Protects Against Myocardial Ischemia Reperfusion Injury by Activating the TLR4/PI3K/Akt Signaling Pathway

Our pilot studies have shown that clemastine fumarate (CLE) can protect against myocardial ischemia-reperfusion injury (MIRI) through regulation of toll like receptor 4 (TLR4). However, the protective mechanism of CLE and related signaling pathways for MIRI remains unclear. The objective of this study is to determine the mechanism by which CLE relieves MIRI in cardiomyocytes and its relationship with the TLR4/PI3K/Akt signaling pathway. CCK8 analysis was used to test the optimal concentration of TLR4 inhibitor CLI-095 and TLR4 agonist lipopolysaccharide (LPS) on MIRI. The expression of inflammatory factors, oxidative stress response, cell damage, and intracellular calcium redistribution of cardiomyocytes were examined using the ELISA kits, Total Superoxide Dismutase Assay Kit with WST-8 and Lipid Peroxidation MDA Assay Kit, LDH Cytotoxicity Assay Kit, and laser scanning confocal microscope. The expression of TLR4/PI3K/Akt and cleaved caspase-3 were determined by Western blotting and immunofluorescent staining. Our results showed that MIRI aggravated the inflammatory response, oxidative stress, cellular damage of cardiomyocytes, and caused redistribution of intracellular calcium, upregulated the expression of TLR4 protein, cleaved caspase-3 protein, and down-regulated the expression of PI3K/Akt protein. After treatment with CLE, the inflammatory response, oxidative stress, and cellular damage of cardiomyocytes were alleviated, and intracellular calcium ion accumulation decreased. The expression of TLR4 protein, cleaved caspase-3 protein declined, but PI3K/Akt protein expression increased in cardiomyocytes treated with CLE. In addition, after treatment with the TLR4 inhibitor CLI-095, the results were similar to those of CLE treatment. The TLR4 agonist LPS aggravated the reactions caused by MIRI. The role of LPS was reversed after CLE treatment. These results suggested that CLE can attenuate MIRI by activating the TLR4/PI3K/Akt signaling pathway.

Salivary Content Might be Associated With Skeletal Status in Postmenopausal Women: SilesiaOsteoActive Study Results

Aim: The aim of the study was to investigate whether salivary mineral content may be associated with bone status in women after menopause. Material and methods: The study group consisted of 125 postmenopausal women aged 64.3 ± 6.9 yr, derived from the epidemiological SilesiaOsteoActive Study. All participants underwent hip and spine bone densitometry using dual energy X-ray absorptiometry, dental examination, and saliva content analysis. Data for salivary pH, copper, calcium, phosphorus, and zinc concentrations were evaluated. Results: Mean femoral neck bone mineral density (BMD) was 0.739 ± 0.118 g/cm2, total hip BMD 0.891 ± 0.14 g/cm2, and spine BMD 0.868 ± 0.14 g/cm2. Salivary pH was significantly lower in women with spinal osteoporosis defined as T-score below −2.5, compared to individuals with normal BMD (pH: 6.65 ± 0.67 vs 6.96 ± 0.58, p < 0.05). There was a significant though weak inverse correlation between Ca concentration in saliva and femoral neck BMD (r = −0.23, p < 0.05). Conclusions: High salivary calcium content and low salivary pH may be indicative of low hip and decreased spine BMD, respectively. These associations may reflect demineralization process (calcium redistribution) influencing bone, and a negative effect of acidity on mineral tissues, although causal pathway remains not clear.

Особливості мінерального обміну у кролів за умови корекції біологічно активними кормовими добавками на тлі імплантування PLA імплантатів

Humic substances are able to influence mineral metabolism due to their properties to form chelate complexes. Directly, the state of bone tissue is closely related to general processes that ensure the exchange of minerals in the body as a whole. Polylactic acid (PLA) is a biopolymer which, due to its high biocompatibility and osseointegration properties, is increasingly used for the manufacture of implants. Among the methods of improving the osseointegration of implants, gaining popularity, the use of pharmacological drugs and dietary supplements that have a direct effect on bone tissue or act indirectly by affecting the body’s systems and metabolism. For the experiment 32 rabbits were divided into groups of 8 rabbits each In two model groups, 16 rabbits were implanted with PLA implants in the bilateral defect of the parietal bone, one of which was immersed in a 1% humilid solution and the other in a 0.9% NaCl solution before administration. From the operated rabbits, 8 received humilid during treatment, and 8 others were intact. 16 rabbits who did not undergo surgery were divided into two groups, one of which drinked humilid and the other clean water. The aim of our work was to determine the mineral metabolism in rabbits during implantation of PLA implants. The ability of humic substances to influence the redistribution of calcium ionized and copper in the blood serum and femur in rabbits of the model group in comparison with intact animals was proved.. There was also an increase in the content of iron and calcium ionized in the serum, and calcium, iron, copper and a decrease in the content of zinc in the femur of rabbits treated with humilide. It has been proved that the introduction of humilid into the diet caused an increase in newly formed bone tissue in PLA implants of rabbits of the model group. Therefore, an increase in macro- microelements in blood serum and their redistribution in the bone tissue of rabbits receiving humilides suggests the possibility of using humilid to correct mineral metabolism and improve the condition of bone tissue. Leveling reduction macro- microelements in the blood and bone tissue, together with an increase in newly formed bone tissue in PLA implants of a model group of rabbits receiving humilide indicate a systemic effect of humilid on the osseointegration of PLA implants.

Clinical and methodological aspects in the diagnosis of magnesium deficiency in patients with paroxysmal atrial fibrillation

Aim. To determine magnesium deficiency in patients with paroxysmal atrial fibrillation using a comprehensive clinical and laboratory approach. Methods. The prospective cohort study included 35 patients of the cardiology department of the Medical association «Novaya bolnitsa». The main group consisted of 22 patients with frequently recurrent paroxysmal atrial fibrillation, the control group - 13 patients without cardiac arrhythmias. The clinical status, Holter-monitoring of the electrocardiogram, the results of the clinical test for magnesium deficiency, laboratory parameters of calcium, magnesium in blood plasma and formed elements, magnesium in whole blood, free fatty acids and plasma osmolarity were evaluated. Results. The clinical score of magnesium deficiency was significantly higher in patients from the main group compared to the control [16.5 (11÷21) vs 13 (8÷15), p &lt;0.001]. In the main group, there was a decrease of magnesium in the whole blood [0.55 (0.5÷0.59) vs 0.61 (0.58÷0.54), p=0.002] and inside the blood cells [0.68 (0.53÷1.29) vs 1.38 (1.29÷1.44), p &lt;0.001]. In patients with atrial fibrillation there is a shift of the ratio of calcium to magnesium in blood plasma [2.5 (2.5÷3) vs 2.9 (2.8÷3.15), p=0.029] and intracellularly [4.85 (2.62÷9.3) vs 1.7 (1.4÷1.95), p=0.002]. The redistribution of calcium and magnesium is influenced not only by the initial concentration of cations, but also by free fatty acids. The best redistribution was obtained when the concentration of free fatty acids was 900 µmol/l, magnesium 1 mmol/l, and calcium 3 mmol/l, which is consistent with the optimal value of cations in the blood plasma. Conclusion. Patients with paroxysmal atrial fibrillation had a significantly lower magnesium content in whole blood and inside the blood cells; magnesium concentration in the cells and in whole blood closely correlated with the results of the clinical test for evaluating magnesium deficiency; intracellular magnesium content can be influenced by the complexing interaction with free fatty acids.

Genetic linkage of corundum plagioclasites–kyshtymites and miaskites of the Ilmenogorsky–Vishnevogorsky complex, South Urals, Russia: new Rb–Sr and Sm–Nd isotopic, geochemical and mineralogical data

New geochemical, mineralogical, and Rb–Sr and Sm–Nd isotopic data have been obtained on corundum plagioclasites–kyshtymites from the 5th Versta deposit (South Urals, Russia). The genetic link of miaskites and kyshtymites is shown. The formation of the kyshtymites is associated with the redistribution and accumulation of aluminum, calcium, HFSE, and LIL-elements at the stage of tectonic-metamorphic deformations of the Ilmenogorsky–Vishnevogorsky alkaline complex.

Effect of Low-Level Laser on Some Metals Related to Redox State and Histological Alterations in the Liver and Kidney of Irradiated Rats

Low-level laser therapy (LLLT) is a type of medicine that uses laser light at low levels to activate the cellular chromophores and the initiation of cellular signaling. This study aimed to evaluate the photomodulation effect of LLL against ionizing radiation (IR)-induced metal disorders related to redox state in the liver and kidney of male rats. Rats were divided into 4 groups (control, LLLT, IR (7Gy), IR+LLLT). The results showed that LLLT 870nm one time for 3days post-irradiation revealed redistribution of iron (Fe), copper (Cu), zinc (Zn),calcium (Ca), magnesium (Mg), manganese (Mn), and selenium (Se) in the liver and kidney tissues. Moreover, LLLT attenuated the oxidative stress manifested by a marked reduction of hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE), total oxidant state (TOS), and oxidative stress index (OSI) associated with a significant increase in total antioxidant status (TAS), glutathione (GSH) content, and glutathione peroxide (GPx), glutathione reductase (GRx), superoxide dismutase(SOD), and catalase (CAT) activities. Moreover, LLLT displayed an increase in glutathione-S-transferase (GSH-T) and ceruloplasmin activities and a decrease in the activity of gamma-glutamyl transferase (γ-GT). Besides, LLLT significantly attenuated the histological changes in the liver and kidney tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes and an improvement in the corpuscles and tubules of the kidney. In conclusion, LLLT could be used as an adjuvant treatment post-exposure to radiation, while it is not beneficial to use it on the normal tissue.

Impaired calcium homeostasis via advanced glycation end products promotes apoptosis through endoplasmic reticulum stress in human nucleus pulposus cells and exacerbates intervertebral disc degeneration in rats.

Previous studies identified advanced glycation end products (AGEs) accumulation in the intervertebral disc (IVD) as an essential risk factor associated with IVD degeneration via accelerated cell apoptosis and impeded extracellular-matrix metabolism; however, the underlying mechanisms have not been fully elucidated. Here, we investigated the effects and mechanisms of AGEs-mediated apoptosis invitro and invivo. We evaluated the effects of AGEs on endoplasmic reticulum (ER) stress, apoptosis, and subcellular calcium (Ca2+ ) redistribution. Our data indicated time- and concentration-dependent upregulation of ER-stress responses in AGEs-treated nucleus pulposus (NP) cells. Additionally, we observed marked suppression of AGEs-mediated apoptosis following the inhibition of ER stress using 4-phenylbutyric acid. Moreover, AGEs-induced sustained cytosolic Ca2+ ([Ca2+ ]c) elevation and ER luminal Ca2+ ([Ca2+ ]er) depletion in a concentration- and time-dependent manner in NP cells. Furthermore, we observed significant increases and decreases in levels of the ER-resident Ca2+ -release channels inositol 1,4,5-triphosphate receptor and ryanodine receptor and ER Ca2+ -reuptake pumps sarco/endoplasmic reticulum Ca2+ -ATPase, respectively. Pharmacologically blocking ER Ca2+ release using Ca2+ antagonists significantly ameliorated Ca2+ dyshomeostasis, ER stress, and subsequent apoptosis in NP cells and partially attenuated the progression of IVD degeneration invivo. These results demonstrated that impaired Ca2+ homeostasis plays an essential role in AGEs-mediated ER stress and subsequent apoptosis in NP cells, with blockage of ER Ca2+ release partially ameliorating subcellular Ca2+ redistribution, ER stress, and apoptosis. Our findings provide novel mechanistic insight into the role of AGEs in the pathogenesis of IVD degeneration and a potential therapeutic strategy.

Genetic Linkage of Corundum Plagioclasites–Kyshtymites and Miaskites of the Ilmenogorsky–Vishnevogorsky Complex, South Urals, Russia: New Rb–Sr and Sm–Nd Isotopic, Geochemical and Mineralogical Data

New geochemical, mineralogical, and Rb–Sr and Sm–Nd isotopic data have been obtained on corundum plagioclasites–kyshtymites from the 5th Versta deposit (South Urals, Russia). The genetic link of miaskites and kyshtymites is shown. The formation of the kyshtymites is associated with the redistribution and accumulation of aluminum, calcium, HFSE, and LIL-elements at the stage of tectonic-metamorphic deformations of the Ilmenogorsky–Vishnevogorsky alkaline complex.

Comparative assessment of bone mineral density in recipients with preserved function and calcium degeneration of heart valve bioprotheses

Aim.To study a bone mineral density (BMD) in recipients with calcium degeneration and preserved morphofunctional state of heart valve bioprotheses (BP).Material and methods.The experimental groups included the patients with structural dysfunctions of BP associated with the calcification of the xenomaterial, confirmed by light and electron microscopy data (group I, n=22) and the patients with normal functional state of the implanted valves according to the results of echocardiographic tests (group II, n=48). BMD was assessed by dual energy absorptiometry in the absolute count of mineralized bone and indicators of T­test.Results. When interpreting the T­test of a femoral neck the severity of osteopenic syndrome prevailed in patients with calcium degeneration of BP (­1,83 [­2,66; ­1,25] in group I vs ­1,47 [­2,51; ­0,86] in group II, р=0,055). At that the mean values of this indicator in patients with the development of calcium­associated BP dysfunctions in the first four years after a surgical correction of the defects reached the diagnostic criteria of the osteoporosis (­2,73 [­3,40; ­2,09] vs ­1,67 [­2,92; ­0,42], р&gt;0,05). According to the result of absorptiometry of the lumbar spine the worst Т­score indicators were also recorded in recipients with the calcification of BP within the first four years of follow­up (­1,75 [­1,83; ­1,43] vs ­0,81 [­0,96; ­0,66] in patients without the signs of calcification, р=0,021). The state of BMD reflects the physiological and pathological processes of calcium redistribution in organism. The existence of the pathogenetic parallels between the activity of bone resorption processes and calcification of the elements of cardiovascular system allows to consider the osteopenia and pathological mineralization of the soft tissues within the framework of a single continuum. The results of the presented work in their turn testify to the determining significance of the severity of osteopenic syndrome manifestations in the development of the “early” calcium degeneration of BP.Conclusion.Extension of the concepts of the mechanisms and processes which form the pathogenetic basis of mineralization will allow to determine the effective strategies for managing the risk of calcium­associated BP dysfunctions.