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1.
Medicine (Baltimore) ; 98(40): e17421, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577757

RESUMO

Regional citrate anticoagulation (RCA) was recommended as the first treatment option for adults by the Kidney Disease Improving Global Outcomes Kidney Foundation in 2012, for the characteristic of sufficient anticoagulation in vitro, but almost no anticoagulation in vivo. Traditionally, the substitute for RCA is calcium-free. This study investigated a simplified protocol of RCA for continuous hemofiltration (CHF) in children using a commercially available substitute containing calcium.An analytical, observational, retrospective study assessed 59 pediatric patients with 106 sessions and 3580 hours of CHF. Values before and after treatment were compared, including Na, ionic calcium (iCa) and HCO3 concentrations, pH, and the ratio of total calcium to iCa (T/iCa). In addition, in vivo and in vitro iCa, treatment time, sessions with continuous transmembrane pressure >200 mm Hg, and sessions with clotting and bleeding were recorded.The average treatment time was 33.8 ±â€Š10.1 hours. In vitro, 88.5% of iCa achieved the target (0.25-0.35 mmol/L), and in vivo, 95.4% of iCa achieved the target (1.0-1.35 mmol/L). There were 8 sessions with a transmembrane pressure >200 mm Hg and 3 sessions with filters clotted. After treatment, there were 2, 1, and 2 sessions with T/iCa > 2.5 (implying citrate accumulation), iCa < 0.9 mmol/L, and iCa > 1.35 mmol/L. No sodium disorders were recorded. There were fewer cases of acidemia and more cases of alkalemia after treatment compared to before.RCA-CHF with a substitute containing calcium and close monitoring could be a safe and effective treatment for children. In addition, the calcium test site in vitro and the adjustment of citrate should be given strict attention.


Assuntos
Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/terapia , Anticoagulantes/farmacocinética , Cálcio/farmacocinética , Ácido Cítrico/farmacocinética , Hemofiltração , Lesão Renal Aguda/etiologia , Anticoagulantes/administração & dosagem , Cálcio/administração & dosagem , Criança , Pré-Escolar , Ácido Cítrico/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
2.
Environ Sci Pollut Res Int ; 26(29): 30472-30484, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444718

RESUMO

The supply of potassium (K) is a strategy to increase the tolerance of plants exposed to Cd toxicity. The aim of this study was to verify the influence of K on the growth and potential of Tanzania guinea grass (Panicum maximum Jacq. cv. Tanzania (syn. Megathyrsus maximus (Jacq.) B.K. Simon & S.W.L. Jacobs)) for Cd phytoextraction as well as to evaluate nutritional attributes of this grass under conditions of Cd stress. The experiment was conducted in a randomized complete block design, using a 3 × 4 factorial arrangement, with three replications. Three rates of K (0.4, 6.0, and 11.6 mmol L-1) were combined with four rates of Cd (0.0, 0.5, 1.0, and 1.5 mmol L-1) in nutrient solution. Two plant growth periods were evaluated. The increase in K supply to plants exposed to Cd rates of up to 1.0 mmol L-1 caused increase in morphogenic and production attributes, as well as reduction in tiller mortality rate, in the second growth period. K concentrations (in both harvests) increased, while calcium and magnesium concentrations in the second harvest decreased with increasing Cd rates. The high availability of Cd (1.5 mmol L-1) in the nutrient solution caused decrease in relative chlorophyll index (RCI) in both harvests. The high supply of K to plants exposed to Cd resulted in high shoot dry mass production, reducing Cd concentration in the photosynthetic tissues (which means great tolerance of the plant) and increasing the accumulation of this metal in the shoots that can be harvested. Therefore, K increases the Cd phytoextraction capacity of Tanzania guinea grass.


Assuntos
Cádmio/isolamento & purificação , Cádmio/toxicidade , Panicum/efeitos dos fármacos , Potássio/farmacologia , Biodegradação Ambiental , Cádmio/farmacocinética , Cálcio/metabolismo , Cálcio/farmacocinética , Clorofila/metabolismo , Magnésio/metabolismo , Magnésio/farmacocinética , Panicum/fisiologia , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Potássio/farmacocinética , Poluentes do Solo/isolamento & purificação , Poluentes do Solo/farmacocinética , Poluentes do Solo/toxicidade , Estresse Fisiológico
3.
Environ Geochem Health ; 41(6): 2763-2775, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31172408

RESUMO

Manganese pollution to plants, soils, and streams from Mn-rich mine spoils is a global and persistent issue. Some former mining sites can be revegetated readily while others struggle to support plants. We explored Mn in plants and soils following 75 years of soil development and reforestation of a pine-northern hardwood forest at the former Betts Mine in western Massachusetts, USA. We studied soils on four Mn-rich mine spoils and at two control sites: an undisturbed location adjacent to the mine and on a non-Mn mineral bearing rock formation to determine if soil conditions have influenced the uptake of Mn and Ca by vegetation. We collected mid-season foliage from five dominant canopy trees and four common understory plants and excavated three soil pits at each site during July 2018. We found that control sites had lower total Mn (980 ± 140 µg g-1) in their soils than on the mine spoil sites (5580 ± 2050 µg g-1). Our soil data indicated that < 1% of total Mn was strong acid extractable at mine spoil soils and control sites. Surprisingly, the canopy trees established on mine spoils at the Betts Mine had equal to or lower foliar Mn concentrations (840 ± 149 µg g-1) and lower Mn/Ca ratios (0.3 ± 0.1 mol mol-1) than at control sites (1667 ± 270 µg g-1; 1.1 ± 0.2 mol mol-1), refuting our hypothesis of mine spoils driving highest Mn uptake. Soil pH and physicochemical properties suggest Mn primarily exists within primary minerals or form insoluble oxides at the mine spoil sites. Our results suggest higher Ca availability and pH in soils likely reduced Mn uptake and promoted reforestation of the mine spoils.


Assuntos
Cálcio/farmacocinética , Manganês/farmacocinética , Plantas/química , Poluentes do Solo/farmacocinética , Solo/química , Cálcio/análise , Concentração de Íons de Hidrogênio , Ferro/análise , Manganês/análise , Massachusetts , Mineração , Poluentes do Solo/análise , Árvores
4.
Nutrients ; 11(5)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064117

RESUMO

Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of vitamin D for bone and general health. The correct method by which to restore normal vitamin D levels is still a matter of debate. Although cholecalciferol remains the most commonly distributed form of vitamin D supplementation worldwide, several drugs with vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of calcifediol on the restoration of normal vitamin D levels. Calcifediol is more soluble than cholecalciferol in organic solvents, due to its high polarity. Good intestinal absorption and high affinity for the vitamin-D-binding protein positively affect the bioavailability of calcifediol compared with cholecalciferol. In particular, orally administered calcifediol shows a much shorter half-life than oral cholecalciferol. Most findings suggest that oral calcifediol is about three- to five-fold more powerful than oral cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly, calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic cytochrome P-450 enzyme system, resulting in decreased synthesis of calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of osteoporosis treatment.


Assuntos
Calcifediol/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Osso e Ossos/metabolismo , Calcifediol/metabolismo , Cálcio/metabolismo , Cálcio/farmacocinética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos
5.
Dalton Trans ; 48(17): 5735-5740, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30972392

RESUMO

At present, though calcium (Ca) reagents with high calcium contents are widely synthesized, their wide application is limited due to their low absorption rates and poor bioavailability. Here we use a carboxymethyl cellulose (CMC) derivative with high water solubility and biocompatibility as a ligand to bind Ca2+. The resulting CaCMC complex exhibits remarkable solubility and absorbability under both basic and acidic conditions as well as in stomach mimicking and the gastrointestinal tract. Importantly, this Ca reagent shows high in vivo calcium bioavailability. Data from osteoporosis mouse models show that the CaCMC complex is superior to calcium carbonate in the treatment of osteoporosis. Therefore, the resulting CaCMC complex is used as a new, highly effective and desirable Ca supplement for daily life and clinical applications.


Assuntos
Materiais Biocompatíveis/farmacocinética , Cálcio/metabolismo , Cálcio/uso terapêutico , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacocinética , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Disponibilidade Biológica , Cálcio/administração & dosagem , Cálcio/farmacocinética , Carboximetilcelulose Sódica/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Solubilidade , Propriedades de Superfície
6.
J Clin Apher ; 34(4): 490-494, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30673128

RESUMO

PURPOSE: During a national shortage of calcium gluconate, we switched to calcium chloride for routine supplementation for peripheral blood stem cell (PBSC) collections. Subsequently, we analyzed the postprocedure ionized calcium level, as we aimed for an equivalent result compared to before the shortage. METHODS: Pharmacy representatives helped us to find an "equivalent" substitute for calcium gluconate at 46.5 mEq in 500 mL normal saline, infused at 100 mL/hour. After instituting a presumably comparable protocol using calcium chloride (40.8 mEq in 250 mL normal saline at a rate of 100 mL/hour), we reviewed ionized calcium results post-PBSC procedures to compare with those obtained with calcium gluconate. Having noticed a difference in the mean values, we adjusted the rate of calcium chloride to reach our desired outcome. RESULTS: Twenty-seven procedures were analyzed on 15 unique patients. We used the Spectra OPTIA with a whole blood: anticoagulant ratio of 13:1. Ionized calcium levels post-PBSC collection with the first calcium chloride protocol were significantly higher (P = 0.003) in nine patients treated. Subsequently, we decreased the calcium chloride infusion rate to 75 mL/hour and achieved similar mean levels to calcium gluconate (P = 0.382). CONCLUSION: Changes in replacement fluids for apheresis procedures can be complex, particularly when dealing with electrolytes that could be clinically significant at critically high or low levels. Once we recognized the need to take into account the amount of elemental calcium infused, we achieved the desired postprocedure ionized calcium results. This study can serve as a lesson for future shortages of infusions used during apheresis procedures.


Assuntos
Gluconato de Cálcio/provisão & distribução , Cálcio/administração & dosagem , Citaferese/métodos , Cálcio/farmacocinética , Cloreto de Cálcio/administração & dosagem , Humanos , Células-Tronco de Sangue Periférico/citologia
7.
Food Funct ; 9(11): 5707-5714, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30311619

RESUMO

Wheat bread is a widely consumed food and is suitable for the introduction of functional ingredients. The aim of this work was to study the effects of bread with garlic and resistant starch as a fiber source on physiological, metabolic, and functional parameters using an in vivo Wistar rat model. Rats were fed with three diets: a control diet prepared according to the American Institute of Nutrition (C), and two semisynthetic diets containing wheat bread (B) and wheat bread with garlic, resistant starch and calcium citrate (BGR). Fresh feces were weighed and lactobacilli (L) and Enterobacteriaceae (E) were analyzed at different times: 1, 20, 45 and 60 days. The pH of the caecal content was recorded and at the end of the study changes in the bone mineral density of total skeleton (ts BMD), femur (F-BMD), spine (S-BMD) and tibia (T-BMD) were determined. Lipoprotein profile was assessed, atherogenic indexes were calculated and malonaldehyde content was measured in the serum and liver. In relation to gut microbiota, the BGR group showed an increase in the L/E ratio with respect to the other groups which was correlated with a lower cecal pH. Besides, the BGR group presented lower weight and a more favourable metabolic profile. In relation to bone measurements, the BGR group presented higher values of ts BMC, ts BMD, F-BMD, and T-BMD than the B group. Thus, bread with resistant starch, garlic and calcium citrate showed a prebiotic effect increasing calcium bioavailability and deposition in bones, compared with wheat bread. The observed beneficial health effects allow us to consider the design of healthier breads.


Assuntos
Pão/análise , Cálcio/farmacocinética , Alho , Amido/química , Triticum/química , Animais , Disponibilidade Biológica , Densidade Óssea , Cálcio/análise , Colesterol/sangue , Enterobacteriaceae/isolamento & purificação , Fezes/química , Fezes/microbiologia , Manipulação de Alimentos , Microbioma Gastrointestinal , Lactobacillus/isolamento & purificação , Masculino , Malondialdeído/sangue , Ratos , Ratos Wistar , Triglicerídeos/sangue
8.
Matern Child Nutr ; 14 Suppl 3: e12649, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30332539

RESUMO

Undernutrition resulting from inadequate access to high-quality, nutritious food is a widespread issue in sub-Saharan Africa impacting the health and survival of mothers and their children. Inadequate dietary intake leads to a deficiency in nutrients including calcium, required for growth and physiological functioning. This study investigated the potential of increasing dietary calcium intake by the addition of heat-treated ground eggshell to locally prepared food. A mixed methods approach of literature review, Delphi expert survey and focus group discussions with women of childbearing age in rural Tanzania, were used to assess the practicality, safety, and acceptability of consumption of ground eggshell. Chicken eggshell has high calcium content (380 mg of calcium/gram) and bioavailability comparable to calcium carbonate (~39%) with 1 g sufficient to provide one half of a sub-Saharan African adult female's dietary calcium needs. Salmonella was indicated as the most likely threat to human health through eggshell consumption. Experts agreed that eggshells boiled for 10 min when preparing hard-boiled eggs with a further 20 min cooking of crushed eggshell in staple foods would eliminate identified egg-associated pathogens. Five focus groups (n = 46) indicated eggshells were perceived as waste. However, there was an indication of general acceptance of the approach and a willingness to consider the incorporation of ground eggshells into their diets. Development of suitable communication methods are required to convey benefits and safe preparation methods. Ground eggshell could be a highly equitable method of increasing calcium intakes across rural sub-Saharan Africa where calcium intake is low and village poultry ownership common.


Assuntos
Casca de Ovo , População Rural , Adolescente , Adulto , África ao Sul do Saara , Animais , Disponibilidade Biológica , Cálcio/análise , Cálcio/deficiência , Cálcio/farmacocinética , Cálcio na Dieta/administração & dosagem , Galinhas , Criança , Pré-Escolar , Culinária/métodos , Casca de Ovo/química , Feminino , Inocuidade dos Alimentos/métodos , Humanos , Lactente , Recém-Nascido , Gravidez , Recomendações Nutricionais , Tanzânia
9.
Environ Sci Pollut Res Int ; 25(36): 36328-36340, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30368704

RESUMO

Chinese flowering cabbage is a commonly consumed vegetable that accumulates Cd easily from Cd-contaminated soils. Cultivations of low-Cd cultivars are promising strategies for food safety, but low-Cd-accumulating mechanisms are not fully elucidated. To address this issue, 37 cultivars were screened to identify high- and low-Cd cultivars upon exposure to sewage-irrigated garden soil pretreated with different Cd concentrations (1.81, 2.90, and 3.70 mg kg-1dry soil). The results showed that shoot Cd concentrations differed among the cultivars by maximum degrees of 2.67-, 3.71-, and 3.00-fold under control and treatments, respectively. Soil-pot trial and hydroponic trial found no significant difference in Cd and Ca mobilization, uptake, and transport ability by root per weight between high- and low-Cd cultivars. Interestingly, a stable R/S ratio difference among cultivars (p < 0.01) was observed, and the cultivar variation of Cd accumulation in shoots was mainly dependent on their R/S ratios. R/S ratio was also statistically positively associated with Cd and Ca accumulation in high- and low-Cd cultivars (p < 0.05), both in soil and hydroponics culture. This was mainly due to the lower root biomass of low-Cd cultivars resulted in lower total release of root exudates, lower total Cd and Ca mobilization in rhizosphere soil, and lower total Cd and Ca uptake and transport. The higher shoot biomass of low-Cd cultivars also has dilution effects on Cd concentration in shoot. Overall, low R/S ratio may be regarded as a direct and efficient indicator of low Cd accumulation in the shoot of Chinese flowering cabbage. These findings provided the possibilities to screening low-Cd cultivars using their R/S ratio.


Assuntos
Brassica/metabolismo , Cádmio/farmacocinética , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Poluentes do Solo/farmacocinética , Brassica/efeitos dos fármacos , Cádmio/análise , Cálcio/farmacocinética , Inocuidade dos Alimentos , Hidroponia , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Rizosfera , Solo , Poluentes do Solo/análise
11.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 53(7): 470-474, 2018 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-29996365

RESUMO

Objective: To evaluate the remineralization effect and mechanism of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) with different concentrations of fluorine on demineralized enamel using electronic probe. Methods: Extracted premolar teeth for orthodontic purpose were immersed into lactic acid gel to prepare artificial white spot lesions (10 teeth in each group). Then the specimens were randomly assigned to three groups: Control group, with 5% of the CPP-ACP+deionized water; Group A with 5% CPP-ACP+500 mg/L F(-) and Group B with 5% CPP-ACP+900 mg/L F(-). The teeth in each group were soaked in different solutions for 4 days and then were measured using electron probe tester. The changes of contents among the three groups were compared. Results: No statistically significant difference in the percentage of fluorine was found in the control group before and after treatment (P=0.06), and the difference in the percentage of fluorine quality in the other two groups was statistically significant (P<0.05). Statistically significant difference was found between calcium oxide and phosphorus peroxide in the three groups before and after mineralization (P<0.05). The percentage change of fluorine mass in group B [(0.107±0.035)%] was significantly greater than that in group A [(0.057±0.038)%] (P<0.05), while fluorine mass in group A was significantly greater than that in control group [(0.013±0.019)%] (P<0.05). In group A and group B, the change in quality of calcium oxide and phosphorus peroxide was significantly greater than that in control group (P<0.05), while no significant difference was found between group A and group B (P>0.05). Conclusions: The addition of fluorine in CPP-ACP increased the transport and penetration of calcium, phosphorus and fluorine on enamel surface.


Assuntos
Caseínas/farmacologia , Esmalte Dentário/efeitos dos fármacos , Flúor/administração & dosagem , Remineralização Dentária/métodos , Dente Pré-Molar , Cálcio/farmacocinética , Compostos de Cálcio/farmacologia , Assistência Odontológica , Esmalte Dentário/fisiologia , Microanálise por Sonda Eletrônica/métodos , Flúor/farmacocinética , Flúor/farmacologia , Humanos , Óxidos/farmacologia , Fósforo/farmacocinética , Compostos de Fósforo/farmacologia , Distribuição Aleatória
12.
Food Funct ; 9(8): 4135-4142, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30019729

RESUMO

In this study, with grass fish bones as the substrate, after flavourzyme treatment, and fermentation with Leuconostoc mesenteroides, a fermentation solution with a high content of soluble calcium was obtained. High performance liquid chromatography and GC-MS analysis indicated that free calcium (11.29 mmol L-1) in the fermentation solution was composed of calcium lactate (3.89 mmol L-1), calcium acetate (6.21 mmol L-1), calcium amino acids and small peptide calcium. Animal experiments show that the fermentation solution of grass fish bones could promote the growth and development of calcium-deficient rats. Complex organic calcium could be well absorbed and utilized by rats so that serum calcium, alkaline phosphatase levels, femur weight and other indicators in calcium-deficient rats could be returned to normal levels. The fermentation solution of grass fish bones can avoid the waste of aquatic proteins and fish bone calcium, and it exhibited high calcium bioavailability. Therefore, the fermentation solution of grass fish bones might be used as a new efficient calcium supplement.


Assuntos
Osso e Ossos/química , Cálcio/farmacocinética , Carpas , Fosfatase Alcalina , Ração Animal/análise , Animais , Densidade Óssea , Cálcio/administração & dosagem , Cálcio/sangue , Cálcio/química , Dieta/veterinária , Fermentação , Manipulação de Alimentos , Leuconostoc mesenteroides/fisiologia , Masculino , Fósforo/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
13.
Drug Deliv Transl Res ; 8(5): 1152-1161, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29752690

RESUMO

Pulsed electric fields (PEFs) are applied as physical stimuli for DNA/drug delivery, cancer therapy, gene transformation, and microorganism eradication. Meanwhile, calcium electrotransfer offers an interesting approach to treat cancer, as it induces cell death easier in malignant cells than in normal cells. Here, we study the spatial and temporal cellular responses to 10 µs duration PEFs; by observing real-time, the uptake of extracellular calcium through the cell membrane. The experimental setup consisted of an inverted fluorescence microscope equipped with a color high-speed framing camera and a specifically designed miniaturized pulsed power system. The setup allowed us to accurately observe the permeabilization of HeLa S3 cells during application of various levels of PEFs ranging from 0.27 to 1.80 kV/cm. The low electric field experiments confirmed the threshold value of transmembrane potential (TMP). The high electric field observations enabled us to retrieve the entire spatial variation of the permeabilization angle (θ). The temporal observations proved that after a minimal permeabilization of the cell membrane, the ionic diffusion was the prevailing mechanism of the delivery to the cell cytoplasm. The observations suggest 0.45 kV/cm and 100 pulses at 1 kHz as an optimal condition to achieve full calcium concentration in the cell cytoplasm. The results offer precise levels of electric fields to control release of the extracellular calcium to the cell cytoplasm for inducing minimally invasive cancer calcium electroporation, an interesting affordable method to treat cancer patients with minimum side effects.


Assuntos
Cálcio/farmacocinética , Membrana Celular/metabolismo , Eletroporação/métodos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Citoplasma/química , Campos Eletromagnéticos , Humanos , Permeabilidade , Análise Espaço-Temporal
14.
Cell Mol Life Sci ; 75(19): 3609-3624, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29700553

RESUMO

Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants. From 1242 human OPN4 variants collated in the NCBI Short Genetic Variation database (dbSNP), we identified 96 that lead to non-synonymous amino acid substitutions. These 96 missense mutations were screened using sequence alignment and comparative approaches to select 16 potentially deleterious variants for functional characterisation using calcium imaging of melanopsin-driven light responses in HEK293T cells. We identify several previously uncharacterised OPN4 mutations with altered functional properties, including attenuated or abolished light responses, as well as variants demonstrating abnormal response kinetics. These data provide valuable insight into the structure-function relationships of human melanopsin, including several key functional residues of the melanopsin protein. The identification of melanopsin variants with significantly altered function may serve to detect individuals with disrupted melanopsin-based light perception, and potentially highlight those at increased risk of sleep disturbance, circadian dysfunction, and visual abnormalities.


Assuntos
Mutação de Sentido Incorreto/fisiologia , Opsinas de Bastonetes/genética , Sequência de Aminoácidos , Substituição de Aminoácidos/fisiologia , Cálcio/farmacocinética , Membrana Celular/metabolismo , Ritmo Circadiano/genética , Análise Mutacional de DNA , Células HEK293 , Humanos , Imagem Óptica , Polimorfismo de Nucleotídeo Único/fisiologia , Transporte Proteico/genética , Opsinas de Bastonetes/química , Opsinas de Bastonetes/metabolismo , Transtornos do Sono do Ritmo Circadiano/genética , Relação Estrutura-Atividade , Transtornos da Visão/genética
15.
Cient. dent. (Ed. impr.) ; 15(1): 53-60, ene.-abr. 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-172861

RESUMO

La superficie de los implantes dentales es un parámetro fundamental a considerar para mejorar la regeneración ósea basada en implantes. Junto con las técnicas quirúrgicas y los materiales y herramientas empleados, las modificaciones superficiales de los implantes han ido evolucionando con el tiempo para permitir acortar los tiempos de tratamiento y abordar reconstrucciones cada vez más complejas. La superficie unicCa® resulta de la incorporación a la superficie multirrugosa optima® de una capa de iones de calcio. Las modificaciones realizadas en el desarrollo de esta nueva superficie hacen que presente ventajas como: impedimento del envejecimiento del óxido de titanio, mejora de la unión hueso-implante y aceleración de la fase de la osteointegración. Para demostrar las propiedades de esta nueva superficie se realizaron estudios en cóndilo femoral de conejo y en tibia de oveja. En ambos casos se demostró un incremento y aceleración de la osteointegración. El calcio, presente en la superficie unicCa®, asegura la estimulación celular desde los primeros momentos tras la implantación hasta la consolidación de los tejidos y la formación de la capa calcificada de osteointegración de la que es el constituyente principal. Esto implica una regeneración peri-implante más rápida y de mejor calidad


The surface of the dental implants is a fundamental parameter to consider for improving bone regeneration based on implants. Together with the surgical techniques and materials and tools used, surface modifications of the implants have evolved over time to allow to shorten treatment times and address increasingly complex reconstructions. The unicCa® surface is the result of the addition to the optima® surface of a layer of calcium ions. The modifications made in the development of this new surface make this advantages such as: impairment of the aging of the titanium oxide, improvement of the union bone-implant and acceleration of the phase of the osseointegration. To demonstrate the properties of this new area studies were performed in rabbit femoral condyle and in tibia of sheep. In both cases showed an increase and acceleration of the osseointegration. The calcium, present on the the unicCa® surface ensures the cellular stimulation from the first moments after implantation until the consolidation of the tissues and the formation of the osseointegration of calcified layer which is the main constituent. This implies a regeneration peri-implant faster and of better quality


Assuntos
Humanos , Implantação Dentária Endo-Óssea/métodos , Osseointegração , Ionóforos de Cálcio/uso terapêutico , Sobrevivência Celular/imunologia , Cálcio/farmacocinética
16.
J Anim Physiol Anim Nutr (Berl) ; 102(3): 789-798, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29393532

RESUMO

To investigate the impact of a selective reduction in dietary phosphorus (P) supply on healthy growing dogs, a total of 23 Beagles and 30 Foxhound crossbreds (FBI) were used in a feeding trial between 6 and 24 weeks of age. Sixteen Beagles and 19 FBI were fed with selectively reduced P concentrations (low phosphorus, LP). The remaining puppies received a completely balanced control diet (CON). With these diets, the P supply in the Beagles at the age of 12 weeks added up to 2.5 ± 0.6 (LP) and 9.8 ± 1.4 g P/kg DM (CON), and in the FBI 4.3 ± 0.9 (LP) and 13.0 ± 1.6 g P/kg DM (CON). Therefore, the LP Beagles received an average of 33 ± 11% of the recommended daily allowances (RDA) of P, the LP FBI 41 ± 11%. The calcium (Ca) concentration stayed unaltered and led to a Ca/P ratio above the recommended range of 1.3/1 to 2/1. The apparent digestibility (aD) of phosphorus was reduced in the LP Beagle; otherwise, the aD of both minerals was not affected by the P concentration of the diet. The renal excretion of P was reduced to zero in both LP groups while the renal calcium excretion increased significantly. Several of the puppies from both breeds showed impaired appetite, growth, skin and fur quality, and a few also clinically showed relevant signs of a disturbed musculoskeletal system after the LP feeding. A rapid loss of muscle strength and posture within hours led to severe deviation of the limb axis with hyperflexion of the joints but no radiological aberrations or signs of pain. Immediate transition of affected puppies to a balanced diet with sufficient phosphorus resulted in a complete recovery of the puppies in less than one month. The results demonstrate the importance of an adequate P supply on the healthy development of growing dogs.


Assuntos
Cálcio/farmacocinética , Cães/crescimento & desenvolvimento , Fósforo na Dieta/administração & dosagem , Fósforo/farmacocinética , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Disponibilidade Biológica , Densidade Óssea/efeitos dos fármacos , Cálcio na Dieta , Dieta/veterinária , Doenças do Cão/induzido quimicamente , Cães/genética , Feminino , Masculino , Desenvolvimento Musculoesquelético , Fósforo/deficiência
17.
Clin Nutr ; 37(6 Pt A): 2068-2075, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29097038

RESUMO

BACKGROUND & AIMS: ß-hydroxy-ß-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) - differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. METHODS: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. RESULTS: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 µM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 µmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 µmol Phe per leg min-1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. CONCLUSIONS: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass.


Assuntos
Cálcio/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Valeratos/metabolismo , Adulto , Disponibilidade Biológica , Cálcio/farmacocinética , Sinalização do Cálcio , Suplementos Nutricionais , Humanos , Masculino , Proteínas Musculares/química , Músculo Esquelético/química , Valeratos/farmacocinética , Adulto Jovem
18.
Int J Biol Macromol ; 110: 294-307, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29097218

RESUMO

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca2+. The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11µm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations.


Assuntos
Alginatos , Cálcio , Portadores de Fármacos , Metotrexato , Alginatos/química , Alginatos/farmacocinética , Alginatos/farmacologia , Animais , Cálcio/química , Cálcio/farmacocinética , Cálcio/farmacologia , Linhagem Celular , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/farmacocinética , Reagentes para Ligações Cruzadas/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ácido Glucurônico/química , Ácido Glucurônico/farmacocinética , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacocinética , Ácidos Hexurônicos/farmacologia , Metotrexato/química , Metotrexato/farmacocinética , Metotrexato/farmacologia , Camundongos
19.
Osteoporos Int ; 29(3): 723-732, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29273827

RESUMO

Intestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH)2D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine. INTRODUCTION: To assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted. METHODS: Forty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 µg/day), 1α hydroxyl calcidiol (ALF; 1 µg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured. RESULTS: The baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH)2D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations. CONCLUSION: These findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate intestinal vitamin D receptors.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Cálcio/farmacocinética , Colecalciferol/farmacologia , Absorção Intestinal/efeitos dos fármacos , Osteoporose Pós-Menopausa/metabolismo , Administração Oral , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Calcitriol/sangue , Colecalciferol/administração & dosagem , Feminino , Humanos , Hidroxicolecalciferóis/administração & dosagem , Hidroxicolecalciferóis/farmacologia , Estudos Prospectivos , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/farmacologia
20.
J Control Release ; 271: 118-126, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29277683

RESUMO

Ciprofloxacin (CIP) apparent permeability across a pulmonary epithelium model can be controlled by the affinity of its complex with a metal cation. The higher the complex affinity, the larger is the reduction in CIP apparent permeability. The aim of this study was to evaluate if the control of the CIP apparent permeability observed in vitro could be transposed in vivo to control the CIP lung-to-blood absorption rate and CIP concentrations in the lung epithelial lining fluid (ELF) after intratracheal (IT) administration. Two types of innovative inhalable microparticles loaded with the low-affinity CIP-calcium complex (CIP-Ca) or with the high-affinity CIP-copper complex (CIP-Cu) were formulated and characterized. Then, ELF and plasma pharmacokinetics of CIP were studied in rats after IT administration of these two types of microparticles and of a CIP solution (2.5mg/kg). The presence of Cu2+ had little effect on the microparticle properties and the dry powder had aerodynamic properties which allowed it to reach the lungs. CIP concentrations in ELF were much higher after CIP-Cu microparticles IT administration compared to the other two formulations, with mean AUCELF to AUCu,plasma ratios equal to 1069, 203 and 9.8 after CIP-Cu microparticles, CIP-Ca microparticles and CIP solution pulmonary administration, respectively. No significant modification of lung toxicity markers was found (lactate dehydrogenase and total protein). CIP complexation with Cu2+ seems to be an interesting approach to obtain high CIP concentrations in the ELF of lungs after dry powder IT administration.


Assuntos
Antibacterianos/administração & dosagem , Cálcio/administração & dosagem , Ciprofloxacino/administração & dosagem , Cobre/administração & dosagem , Pulmão/metabolismo , Administração por Inalação , Aerossóis , Animais , Antibacterianos/farmacocinética , Cálcio/farmacocinética , Ciprofloxacino/farmacocinética , Cobre/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Masculino , Pós , Ratos Sprague-Dawley
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