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1.
Rev Environ Contam Toxicol ; 251: 1-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31011831

RESUMO

Heavy metal pollution in surface water is a global environmental problem. This study analyzed the trends, health risks, and sources of eight dissolved heavy metal species in river and lake water across five continents (Africa, Asia, Europe, North America, and South America; Oceania was excluded owing to a lack of data) for the period 1970-2017. We wanted to assess the effects of various implemented countermeasures to pollution and to determine those that could be adopted worldwide. Collectively, the water system showed increasing trends for Cd, Cr, Cu, Ni, Mn, and Fe and decreasing trends for Pb and Zn. The mean dissolved concentrations of most heavy metals were highest in Asia and lowest in Europe. Most heavy metals had low non-carcinogenic risks over this period. The cancer risks associated with Pb were lower than the hazardous level on all five continents over the five decades, whereas the cancer risks related to Cr exceeded the hazardous level in the 1970s, 2000s, and 2010s, and in Africa, Asia, and North America over the entire period. Mining and manufacturing were consistently found to be critical sources of metal pollution from 1970 to 2017. However, the heavy metal sources differed significantly by continent, with waste discharge and rock weathering dominant in Africa; mining and manufacturing, along with rock weathering, are dominant in Asia and South America; fertilizer and pesticide use, along with rock weathering, are dominant in North America; and mining and manufacturing, waste discharge, and rock weathering are dominant in Europe. Global trends in the metal loadings in water and in relevant pollution-control measures suggest that countermeasures in Europe have successfully controlled heavy metal pollution. The successful measures include implementing rigorous standards for metal emissions, limiting the metal concentrations in products, and rigorously treating metal-contaminated waste. Therefore, the measures implemented in Europe should be extended worldwide to treat heavy metal pollution in water.


Assuntos
Exposição Ambiental/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental , Humanos , Lagos , Rios
2.
Rev Environ Contam Toxicol ; 251: 131-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31129734

RESUMO

Maternal exposure to endocrine-disrupting chemicals (EDCs) is associated with long-term hormone-dependent effects that are sometimes not revealed until maturity, middle age, or adulthood. The aim of this study was to conduct descriptive reviews on animal experimental and human epidemiological evidence of the adverse health effects of in utero and lactational exposure to selected EDCs on the first generation and subsequent generation of the exposed offspring. PubMed, Web of Science, and Toxline databases were searched for relevant human and experimental animal studies on 29 October 29 2018. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated and qualitative data extracted for analysis. The search yielded 73 relevant human and 113 animal studies. Results from studies show that in utero and lactational exposure to EDCs is associated with impairment of reproductive, immunologic, metabolic, neurobehavioral, and growth physiology of the exposed offspring up to the fourth generation without additional exposure. Little convergence is seen between animal experiments and human studies in terms of the reported adverse health effects which might be associated with methodologic challenges across the studies. Based on the available animal and human evidence, in utero and lactational exposure to EDCs is detrimental to the offspring. However, more human studies are necessary to clarify the toxicological and pathophysiological mechanisms underlying these effects.


Assuntos
Disruptores Endócrinos , Exposição Materna/estatística & dados numéricos , Animais , Feminino , Humanos , Gravidez
3.
Food Chem ; 302: 125296, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400698

RESUMO

The process of manufacturing infant milk formulas (IMFs) involves heat treatments that can lead to whey protein denaturation. The objective of the study was to determine how protein composition affects the denaturation kinetics of the whey proteins within IMFs. Three model IMFs (1.3% of cow's milk protein) were produced with a caseins: whey proteins ratio of 40:60, differing only by the whey protein composition. The kinetics of heat-induced denaturation of α-lactalbumin, ß-lactoglobulin and lactoferrin were investigated between 67.5 °C and 80 °C by chromatographic quantification of the residual native proteins. Results showed that the heat-denaturation of α-lactalbumin was reduced when ß-lactoglobulin was absent. The heat-denaturation of lactoferrin was not affected by the composition of the IMFs but its presence enhanced the heat-denaturation of ß-lactoglobulin. This study revealed that, for higher heat treatments (90 °C/15 s, 75 °C/15 min), IMF containing α-lactalbumin and lactoferrin preserved a higher proportion of native whey proteins than IMFs containing ß-lactoglobulin.


Assuntos
Temperatura Alta , Fórmulas Infantis/química , Desnaturação Proteica , Proteínas do Soro do Leite/química , Animais , Bovinos , Humanos , Lactente , Cinética
4.
Food Chem ; 302: 125186, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400700

RESUMO

Enzymatic processing could reduce the allergenicity of peanut proteins while may lose the functional properties. Transglutaminase (TGase) is an enzyme for improving the functional properties of proteins/hydrolysates. No studies have been conducted on peanut hydrolysates that are crosslinked with TGase. In this study, allergenicity and functional properties of peanut protein hydrolysate cross-linked by TGase were tested. Papain, ficin and bromelain were selected out of eight food-grade enzymes for the kinetic analysis of peanut protein hydrolysis that lead to high reduction rate (K) of the IgE-binding property. Peanuts hydrolyzed by the three selected enzymes (200 AzU/g) were used for IgE binding, TGase-crosslinking and functional property characterization. After hydrolysis, the IgE-binding properties of the peanut soluble extracts were decreased (by 85%-95%); and functional properties were also decreased as compared to intact peanut protein extracts. The TGase crosslinked hydrolysates had similar IgE-binding properties to the un-crosslinked hydrolysates, but with higher functional properties.


Assuntos
Alérgenos/metabolismo , Arachis/imunologia , Proteínas de Plantas/metabolismo , Transglutaminases/metabolismo , Alérgenos/imunologia , Humanos , Hidrólise , Imunoglobulina E/metabolismo , Cinética , Proteínas de Plantas/imunologia
5.
Food Chem ; 302: 125328, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404868

RESUMO

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0-fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Emulsificantes/química , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Digestão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Lipídeos/química , Masculino , Nanopartículas/administração & dosagem , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/química
6.
Food Chem ; 302: 125332, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404871

RESUMO

Wheat bran (WB) was treated using xylanase and arabinofuranosidase from Thermotoga maritima and added to steamed breads on 15% flour weight basis. The antioxidant capacity and water and oil retention capacity of brans were increased while their soluble xylooligosaccharides and phenolic acids content were increased. Two enzymes treatment was found to be more effective in decreasing the resistance to extension, softening degree, water absorption and development time, and in increasing the extensibility, stability time, porosity and sensorial characteristics of the steamed breads. Two enzymes treatment had significantly (P < 0.05) greater specific volume, springiness and cohesiveness and lower crumb firmness, gumminess, chewiness than single enzyme treatment. All results highlighted that combination of xylanase and arabinofuranosidase can improve the degrees hydrolysis of WB and its soluble AX xylooligosaccharides produced, having a synergetic effect on the dough rheology and nutritional and quality characteristics of steamed bread.


Assuntos
Pão , Fibras na Dieta , Endo-1,4-beta-Xilanases/química , Glicosídeo Hidrolases/química , Antioxidantes/análise , Antioxidantes/química , Fibras na Dieta/análise , Farinha , Qualidade dos Alimentos , Humanos , Hidrólise , Valor Nutritivo , Reologia , Vapor , Paladar , Triticum
7.
Toxicol Lett ; 318: 86-91, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669099

RESUMO

Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.


Assuntos
Anemia Ferropriva/induzido quimicamente , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Duodeno/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepcidinas/metabolismo , Absorção Intestinal/efeitos dos fármacos , Ferro/sangue , Inibidores da Bomba de Prótons/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Anemia Ferropriva/sangue , Anemia Ferropriva/fisiopatologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Transporte de Cátions/metabolismo , Duodeno/metabolismo , Duodeno/fisiopatologia , Células Hep G2 , Hepatócitos/metabolismo , Antagonistas dos Receptores Histamínicos H2/toxicidade , Humanos , Ferro/deficiência , Masculino , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/genética
8.
Toxicol Lett ; 318: 92-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678399

RESUMO

Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48 h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2nd and 4th days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4th and 5th days. Thrombocytopenia was observed in 75% of patients between 4th and 6th days for mild cases and between 9th and 11th days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11th and 12th days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.


Assuntos
Medula Óssea/efeitos dos fármacos , Terrorismo Químico , Substâncias para a Guerra Química/envenenamento , Leucocitose/induzido quimicamente , Leucopenia/induzido quimicamente , Linfopenia/induzido quimicamente , Gás de Mostarda/envenenamento , Trombocitopenia/induzido quimicamente , Adolescente , Adulto , Biomarcadores/sangue , Medula Óssea/patologia , Feminino , Hemoglobinas/metabolismo , Humanos , Leucocitose/sangue , Leucocitose/patologia , Leucopenia/sangue , Leucopenia/patologia , Linfopenia/sangue , Linfopenia/patologia , Masculino , Síria , Trombocitopenia/sangue , Trombocitopenia/patologia , Adulto Jovem
9.
Einstein (Sao Paulo) ; 18: eGS4442, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576910

RESUMO

OBJECTIVE: To analyze the legal demands of tiotropium bromide to treat chronic obstructive pulmonary disease. METHODS: We included secondary data from the pharmaceutical care management systems made available by the Paraná State Drug Center. RESULTS: Public interest civil action and ordinary procedures, among others, were the most common used by the patients to obtain the medicine. Two Health Centers in Paraná (Londrina and Umuarama) concentrated more than 50% of the actions. The most common specialty of physicians who prescribed (33.8%) was pulmonology. There is a small financial impact of tiotropium bromide on general costs with medicines of the Paraná State Drug Center. However, a significant individual financial impact was observed because one unit of the medicine represents 38% of the Brazilian minimum wage. CONCLUSION: Our study highlights the need of incorporating this medicine in the class of long-acting anticholinergic bronchodilator in the Brazilian public health system.


Assuntos
Broncodilatadores/economia , Medicamentos Essenciais/provisão & distribução , Necessidades e Demandas de Serviços de Saúde/legislação & jurisprudência , Função Jurisdicional , Doença Pulmonar Obstrutiva Crônica/economia , Brometo de Tiotrópio/economia , Brasil , Medicamentos Essenciais/economia , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/legislação & jurisprudência , Acesso aos Serviços de Saúde/tendências , Necessidades e Demandas de Serviços de Saúde/economia , Necessidades e Demandas de Serviços de Saúde/tendências , Humanos , Programas Nacionais de Saúde , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo
10.
Rev Environ Contam Toxicol ; 252: 97-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31346776

RESUMO

Human milk may sometimes contain chemical contaminants, which could have adverse effects on neonates or nursing infants. Lead (Pb) is of considerable interest due to its toxicity and occurrence. Furthermore, it has been suggested that human milk is a significant potential source of lead exposure to nursing infants. A systematic literature search in PubMed, Science Direct, and Google Scholar databases was performed to identify relevant studies, published in English until 2017, that investigated and explored common factors affecting the level of lead in human milk among lactating women around the world. Forty-nine papers were rated and explored the effect of one or several factors on the level of lead in human milk from 28 countries and carried out over a wide time frame from 1983 to 2017 and through Europe, Asia, America, and Africa, reviewing more than 5,000 subjects. Place of residence, maternal age, stage of lactation, smoking habits, maternal dietary intakes, and parity were the mostly assessed factors among the studies and considered as the main factors affecting Pb levels in BM. Other factors were not studied well enough and considered minor because few surveys evaluated their impacts. However, the literature findings are very controversial.


Assuntos
Poluentes Ambientais/metabolismo , Lactação , Chumbo/metabolismo , Leite Humano/metabolismo , Feminino , Humanos , Recém-Nascido , Gravidez
11.
Einstein (Sao Paulo) ; 18: eAO4739, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31553355

RESUMO

OBJECTIVE: To use magnetic resonance imaging to assess the prevalence of foot and ankle ligament injuries and fractures associated with ankle sprain and not diagnosed by x-ray. METHODS: We included 180 consecutive patients with a history of ankle sprain, assessed at a primary care service in a 12-month period. Magnetic resonance imaging findings were recorded and described. RESULTS: Approximately 92% of patients had some type of injury shown on the magnetic resonance imaging. We found 379 ligament injuries, 9 osteochondral injuries, 19 tendinous injuries and 51 fractures. Only 14 magnetic resonance imaging tests (7.8%) did not show any sort of injury. We observed a positive relation between injuries of the lateral complex, syndesmosis and medial ligaments. However, there was a negative correlation between ankle ligament injuries and midfoot injuries. CONCLUSION: There was a high rate of injuries secondary to ankle sprains. We found correlation between lateral ligament injuries and syndesmosis and deltoid injuries. We did not observe a relation between deltoid and syndesmosis injuries or between lateral ligamentous and subtalar injuries. Similarly, no relation was found between ankle and midfoot injuries.


Assuntos
Traumatismos do Tornozelo/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Traumatismos do Tornozelo/diagnóstico por imagem , Brasil/epidemiologia , Cartilagem Articular/lesões , Criança , Feminino , Humanos , Ligamentos Laterais do Tornozelo/lesões , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
12.
Einstein (Sao Paulo) ; 18: eRC5063, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31553357

RESUMO

A 65-year-old male with a history of urinary tract trauma requiring cystotomy and chronic bladder catheterization, presenting with chronic and uninvestigated changes in the color of the urine bag system, with no urine color change, and positive urine culture for Proteus mirabilis . These characteristics refer to the purple urine bag syndrome, a not weel-known condition, with a benign course in most cases, and associated with urinary tract infection in patients with chronic bladder catheterization. Although it is characterized by marked changes, it is underdiagnosed by healthcare professionals.


Assuntos
Infecções Relacionadas a Cateter/microbiologia , Coletores de Urina/efeitos adversos , Infecções Urinárias/microbiologia , Idoso , Infecções Relacionadas a Cateter/patologia , Humanos , Masculino , Proteus mirabilis/isolamento & purificação , Fatores de Risco , Síndrome , Infecções Urinárias/patologia , Urina/microbiologia
13.
Einstein (Sao Paulo) ; 18: eGS4913, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31531556

RESUMO

OBJECTIVE: To evaluate indications, results and strategy of retinal exams requested at Primary Care Units. METHODS: A retrospective study that analyzed the indications and results of retinal exams, in the modalities clinical dilated fundus exams and color fundus photographs. In the following situations, patients were considered eligible for color fundus photographs if visual acuity was normal and ocular symptoms were absent: diabetes mellitus and/or hypertension, in use of drugs with potential retinal toxicity, diagnosis or suspicion of glaucoma, stable and asymptomatic retinopathies, except myopia greater than -3.00 diopters. RESULTS: A total of 1,729 patients were evaluated (66% female, age 63.5±15.5 years), and 1,190 underwent clinical dilated fundus exam and 539 underwent color fundus photographs. Diabetes was present in 32.2%. The main indications were diabetes (23.7%) and glaucoma evaluation (23.5%). In 3.4% of patients there was no apparent indication. The main results were a large cup/disc ratio (30.7%) and diabetic retinopathy (13.2%). Exam was normal in 9.6%, detected peripheral changes in 7% and could not be performed in 1%. Considering patients eligible for fundus photographs (22.4%), more than half underwent clinical dilated fundus exams. CONCLUSION: Regarding exam modality, there were no important differences in the distribution of indications or diagnosis. Color fundus photograph is compatible with telemedicine and more cost-effective, and could be considered the strategy of choice in some scenarios. Since there are no clear guidelines for retinal exams indications or the modality of choice, this study may contribute to such standardization, in order to optimize public health resources.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Atenção Primária à Saúde/estatística & dados numéricos , Retina , Doenças Retinianas/diagnóstico , Idoso , Retinopatia Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico/economia , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Fotografação , Exame Físico , Estudos Retrospectivos , Telemedicina , Acuidade Visual
14.
Einstein (Sao Paulo) ; 18: eRC4582, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31531557

RESUMO

The correct identification of erythrocyte antibodies is fundamental for the searching for compatible blood and haemolytic transfusion reactions prevention. Antibodies against antigens of high prevalence are difficult to identify because of the rarity of their occurrence and unavailability of negative red cells for confirmation. We report a case of 46-years-old woman, diagnosed with hemoglobinopathy, and who had symptomatic fall in hemoglobin levels (5.3g/dL) after blood transfusion suggestive of transfusion reaction. The patient's blood type was O RhD-positive. Irregular antibody screening was positive and demonstrated a panreaction against all erythrocytes tested, but this result was not reactive with dithiothreitol. Using negative red cells for antigens of high prevalence of our inventory we could identify in the serum of the same erythrocytes an anti-Holley antibody associated with anti-E. Molecular analysis confirmed that the patient was negative for E and Holley antigens. The crossmath with compatible units confirmed the results. Holley is a high prevalence antigen of the Dombrock blood system whose negative phenotype is extremely rare in all populations and is associated with hemolytic transfusion reactions. This is an antibody that is difficult to identify because laboratories need to have experience in solving complex cases, and have available a large stock of rare sera and erythrocytes, as well other tools such as enzymes, thiol reagents and molecular tests. The correct identification of a rare antibody is initial and mandatory for searching of compatible donors, and to guarantee a satisfactory transfusional support.


Assuntos
Anticorpos/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Reação Transfusional/imunologia , Anticorpos/sangue , Eritrócitos/imunologia , Feminino , Testes Hematológicos/métodos , Humanos , Imunoglobulinas/sangue , Isoanticorpos/imunologia , Pessoa de Meia-Idade
15.
Adv Exp Med Biol ; 1131: 1-6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646504

RESUMO

Calcium signaling and its interacting networks are involved in mediating numerous processes including gene expression, excitation-contraction coupling, stimulus-secretion coupling, synaptic transmission, induction of synaptic plasticity, and embryonic development. Many structures, organelles, receptors, channels, calcium-binding proteins, pumps, transporters, enzymes, and transcription factors are involved in the generation and decoding of the different calcium signals in different cells. Powerful methods for measuring calcium concentrations, advanced statistical methods, and biophysical simulations are being used for modelling calcium signals. Calcium signaling is being studied in many cells, and in many model organisms to understand the mechanisms of many physiological processes, and the pathogenesis of many diseases, including cancers, diabetes, and neurodegenerative disorders. Studies in calcium signaling are being used for understanding the mechanisms of actions of drugs, and for discovery of new drugs for the prevention and treatment of many diseases.


Assuntos
Sinalização do Cálcio , Animais , Sinalização do Cálcio/fisiologia , Humanos
16.
Adv Exp Med Biol ; 1131: 7-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646505

RESUMO

Measuring free Ca2+ concentration ([Ca2+]) in the cytosol or organelles is routine in many fields of research. The availability of membrane permeant forms of indicators coupled with the relative ease of transfecting cell lines with biological Ca2+ sensors have led to the situation where cellular and subcellular [Ca2+] is examined by many non-specialists. In this chapter, we evaluate the most used Ca2+ indicators and highlight what their major advantages and disadvantages are. We stress the potential pitfalls of non-ratiometric techniques for measuring Ca2+ and the clear advantages of ratiometric methods. Likely improvements and new directions for Ca2+ measurement are discussed.


Assuntos
Cálcio , Citosol , Organelas , Animais , Cálcio/metabolismo , Técnicas Citológicas , Citosol/química , Citosol/metabolismo , Humanos , Organelas/química , Organelas/metabolismo
17.
Adv Exp Med Biol ; 1131: 27-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646506

RESUMO

Ca2+, Na+ and K+- permeable ion channels as well as GPCRs linked to Ca2+ release are important drug targets. Accordingly, high-throughput fluorescence plate reader assays have contributed substantially to drug discovery efforts and pharmacological characterization of these receptors and ion channels. This chapter describes some of the basic properties of the fluorescent dyes facilitating these assay approaches as well as general methods for establishment and optimisation of fluorescence assays for ion channels and Gq-coupled GPCRs.


Assuntos
Bioensaio , Canais Iônicos , Receptores Acoplados a Proteínas-G , Animais , Bioensaio/tendências , Descoberta de Drogas , Corantes Fluorescentes/metabolismo , Humanos , Canais Iônicos/análise , Receptores Acoplados a Proteínas-G/análise
18.
Adv Exp Med Biol ; 1131: 73-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646507

RESUMO

Imaging techniques may overcome the limitations of electrode techniques to measure locally not only membrane potential changes, but also ionic currents. Here, we review a recently developed approach to image native neuronal Ca2+ currents from brain slices. The technique is based on combined fluorescence recordings using low-affinity Ca2+ indicators possibly in combination with voltage sensitive dyes. We illustrate how the kinetics of a Ca2+ current can be estimated from the Ca2+ fluorescence change and locally correlated with the change of membrane potential, calibrated on an absolute scale, from the voltage fluorescence change. We show some representative measurements from the dendrites of CA1 hippocampal pyramidal neurons, from olfactory bulb mitral cells and from cerebellar Purkinje neurons. We discuss the striking difference in data analysis and interpretation between Ca2+ current measurements obtained using classical electrode techniques and the physiological currents obtained using this novel approach. Finally, we show how important is the kinetic information on the native Ca2+ current to explore the potential molecular targets of the Ca2+ flux from each individual Ca2+ channel.


Assuntos
Canais de Cálcio , Neuroimagem , Animais , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Dendritos/fisiologia , Humanos , Potenciais da Membrana/fisiologia , Imagem Óptica , Células Piramidais/fisiologia
19.
Adv Exp Med Biol ; 1131: 93-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646508

RESUMO

Plasma membrane Ca2+ transport ATPases (PMCA1-4, ATP2B1-4) are responsible for removing excess Ca2+ from the cell in order to keep the cytosolic Ca2+ ion concentration at the low level essential for normal cell function. While these pumps take care of cellular Ca2+ homeostasis they also change the duration and amplitude of the Ca2+ signal and can create Ca2+ gradients across the cell. This is accomplished by generating more than twenty PMCA variants each having the character - fast or slow response, long or short memory, distinct interaction partners and localization signals - that meets the specific needs of the particular cell-type in which they are expressed. It has become apparent that these pumps are essential to normal tissue development and their malfunctioning can be linked to different pathological conditions such as certain types of neurodegenerative and heart diseases, hearing loss and cancer. In this chapter we summarize the complexity of PMCA regulation and function under normal and pathological conditions with particular attention to recent developments of the field.


Assuntos
Membrana Celular , ATPases Transportadoras de Cálcio da Membrana Plasmática , Animais , Membrana Celular/enzimologia , Membrana Celular/patologia , Citosol/metabolismo , Homeostase/fisiologia , Humanos , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo
20.
Adv Exp Med Biol ; 1131: 131-161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646509

RESUMO

Calcium (Ca2+) is a fundamental regulator of cell fate and intracellular Ca2+ homeostasis is crucial for proper function of the nerve cells. Given the complexity of neurons, a constellation of mechanisms finely tunes the intracellular Ca2+ signaling. We are focusing on the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) pump, an integral ER protein. SERCA's well established role is to preserve low cytosolic Ca2+ levels ([Ca2+]cyt), by pumping free Ca2+ ions into the ER lumen, utilizing ATP hydrolysis. The SERCA pumps are encoded by three distinct genes, SERCA1-3, resulting in 12 known protein isoforms, with tissue-dependent expression patterns. Despite the well-established structure and function of the SERCA pumps, their role in the central nervous system is not clear yet. Interestingly, SERCA-mediated Ca2+ dyshomeostasis has been associated with neuropathological conditions, such as bipolar disorder, schizophrenia, Parkinson's disease and Alzheimer's disease. We summarize here current evidence suggesting a role for SERCA in the neurobiology of neuropsychiatric and neurodegenerative disorders, thus highlighting the importance of this pump in brain physiology and pathophysiology.


Assuntos
Encéfalo , Retículo Endoplasmático , Doenças do Sistema Nervoso , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Encéfalo/enzimologia , Encéfalo/patologia , Retículo Endoplasmático/enzimologia , Regulação Enzimológica da Expressão Gênica , Homeostase , Humanos , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/fisiopatologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
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