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1.
Chemosphere ; 263: 128021, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33078709

RESUMEN

BACKGROUND: Metals play an important role in type 2 diabetes mellitus (T2DM). This study aimed to explore the association of T2DM risk with single metal exposure and multi-metal co-exposure. METHODS: A case-control study with 223 T2DM patients and 302 controls was conducted. Serum concentrations of 19 metals were determined by inductively coupled plasma mass spectrometry (ICP-MS). Those metals with greater effects were screened out and co-exposure effects of metals were assessed by least absolute shrinkage and selection operator (LASSO) regression. RESULTS: Serum calcium (Ca), selenium (Se) and vanadium (V) were found with greater effects. Higher levels of Ca and Se were associated with increased T2DM risk (OR = 2.23, 95%CI: 1.38-3.62, Ptrend = 0.002; OR = 3.16, 95%CI: 1.82-5.50, Ptrend < 0.001), but higher V level was associated with decreased T2DM risk (OR = 0.58, 95%CI: 0.34-0.97, Ptrend < 0.001). Serum Ca and V concentrations were nonlinearly associated with T2DM risk (Poverall < 0.001, Pnonliearity < 0.001); however, Se concentration was linearly associated with T2DM risk (Poverall < 0.001, Pnonliearity = 0.389). High co-exposure score of serum Ca, Se and V was associated with increased T2DM risk (OR = 3.50, 95%CI: 2.08-5.89, Ptrend < 0.001) as a non-linear relationship (Poverall < 0.001, Pnonliearity = 0.003). CONCLUSIONS: This study suggest that higher levels of serum Ca and Se were associated with increased T2DM risk, but higher serum V level was associated with decreased T2DM risk. Moreover, co-exposure of serum Ca, Se and V was nonlinearly associated with T2DM risk, and high co-exposure score was positively associated with T2DM risk.


Asunto(s)
Calcio/toxicidad , Diabetes Mellitus Tipo 2/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/toxicidad , Selenio/toxicidad , Vanadio/toxicidad , Adulto , Pueblo Asiatico , Calcio/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Contaminantes Ambientales/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selenio/sangre , Vanadio/sangre
2.
Brain ; 142(9): 2737-2755, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31302671

RESUMEN

Poor vitamin D status is associated with a higher relapse rate and earlier disability in multiple sclerosis. Based on these associations, patients with multiple sclerosis are frequently supplemented with the vitamin D precursor cholecalciferol, although it is unclear whether this regimen is of therapeutic benefit. To model consequences of this common practice, mice were fed for more than 3 months with a low, medium or high dose of cholecalciferol, representative of vitamin D deficiency, modest and disproportionally high supplementation, respectively, in patients with multiple sclerosis. Compared to vitamin D-deprived mice, its moderate supplementation reduced the severity of subsequent experimental autoimmune encephalomyelitis, which was associated with an expansion of regulatory T cells. Direct exposure of murine or human T cells to vitamin D metabolites inhibited their activation. In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/l developed fulminant experimental autoimmune encephalomyelitis with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells. When dissecting this unexpected outcome, we observed that high, but not medium dose vitamin D had caused mild hypercalcaemia, which rendered T cells more prone to pro-inflammatory activation. Exposing murine or human T cells to equivalent calcium concentrations in vitro enhanced its influx, triggering activation, upregulation of pro-inflammatory gene products and enhanced transmigration across a blood-brain barrier model. These findings suggest that vitamin D at moderate levels may exert a direct regulatory effect, while continuous high dose vitamin D treatment could trigger multiple sclerosis disease activity by raising mean levels of T-cell excitatory calcium.


Asunto(s)
Autoinmunidad/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de los fármacos , Vitamina D/toxicidad , Animales , Barrera Hematoencefálica , Calcifediol/sangre , Calcio/sangre , Calcio/uso terapéutico , Calcio/toxicidad , Cloruros/sangre , Colecalciferol/efectos adversos , Colecalciferol/uso terapéutico , Relación Dosis-Respuesta a Droga , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Humanos , Hipercalcemia/inducido químicamente , Hipercalcemia/inmunología , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/inmunología , Fosfatos/sangre , Sodio/sangre , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/inmunología
3.
Acupunct Med ; 36(6): 401-407, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30257960

RESUMEN

BACKGROUND: The hippocampus is vulnerable to severe damage after cerebral ischaemia-reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO). METHODS: 60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1-20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting. RESULTS: Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033). CONCLUSIONS: EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.


Asunto(s)
Calcio/toxicidad , Disfunción Cognitiva/terapia , Electroacupuntura , Daño por Reperfusión/terapia , Animales , Disfunción Cognitiva/etiología , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Infarto de la Arteria Cerebral Media , Masculino , Aprendizaje por Laberinto , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/fisiopatología
4.
Cancer Res ; 77(2): 355-365, 2017 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-27879271

RESUMEN

Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355-65. ©2016 AACR.


Asunto(s)
Calcio/toxicidad , Colecalciferol/farmacología , Dieta/efectos adversos , Neoplasias de la Próstata/patología , Receptores Sensibles al Calcio/metabolismo , Canales Catiónicos TRPC/metabolismo , Animales , Línea Celular Tumoral , Suplementos Dietéticos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Canal Catiónico TRPC6 , Regulación hacia Arriba
5.
Food Chem ; 211: 409-14, 2016 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-27283649

RESUMEN

Pretreatments such as low temperature blanching and/or calcium soaking affect the cooked texture of vegetal food. In the work, lotus rhizomes (Nelumbo nucifera Gaertn.) were pretreated using the following 4 treatments, blanching at 40°C, blanching at 90°C, soaking in 0.5% CaCl2, and blanching at 40°C followed by immersion in 0.5% CaCl2. Subsequently, the cell wall material of pretreated samples was isolated and fractioned to identify changes in the degree of esterification (DE) and monosaccharide content of each section, and the texture of the lotus rhizomes in different pre-treatments was determined after thermal processing with different time. The results showed that the greatest hardness was obtained after blanching at 40°C in CaCl2, possibly attributing to the formation of a pectate calcium network, which maintains the integrity of cell walls. Furthermore, the content of galactose, rhamnose and arabinose decreased due to the breakage of sugar backbones and subsequent damage to cell walls. Our results may provide a reference for lotus rhizome processing.


Asunto(s)
Calcio/toxicidad , Calor/efectos adversos , Nelumbo/química , Nelumbo/efectos de los fármacos , Rizoma/química , Rizoma/efectos de los fármacos , Antioxidantes/análisis , Antioxidantes/química , Calcio/administración & dosificación , Fenómenos Químicos/efectos de los fármacos , Extractos Vegetales/análisis , Extractos Vegetales/química
6.
Neurotox Res ; 30(3): 380-91, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27126806

RESUMEN

Alternatives for the treatment of amyotrophic lateral sclerosis (ALS) are scarce and controversial. The etiology of neuronal vulnerability in ALS is being studied in motor neuron-like NSC-34 cells to determine the underlying mechanisms leading to selective loss of motor neurons. One such mechanism is associated with mitochondrial oxidative stress, Ca(2+) overload, and low expression of Ca(2+)-buffering proteins. Therefore, in order to elicit neuronal death in ALS, NSC-34 cells were exposed to the following cytotoxic agents: (1) a mixture of oligomycin 10 µM and rotenone 30 µM (O/R), or (2) phenylarsine oxide 1 µM (PAO) (to mimic excess free radical production during mitochondrial dysfunction), and (3) veratridine 100 µM (VTD) (to induce overload of Na(+) and Ca(2+) and to alter distribution of Ca(2+)-buffering proteins [parvalbumin and calbindin-D28k]). Thus, the aim of the study was to test the novel neuroprotective compound ITH33/IQM9.21 (ITH33) and to compare it with riluzole on in vitro models of neurotoxicity. Cell viability measured with MTT showed that only ITH33 protected against O/R at 3 µM and PAO at 10 µM, but not riluzole. ITH33 and riluzole were neuroprotective against VTD, blocked the maximum peak and the number of [Ca(2+)]c oscillations per cell, and restored the effect on parvalbumin. However, only riluzole reversed the effect on calbindin-D28k levels. Therefore, ITH33 was neuroprotective against oxidative stress and Na(+)/Ca(2+) overload, both of which are involved in ALS.


Asunto(s)
Benzamidas/farmacología , Glutamatos/farmacología , Neuronas Motoras/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Arsenicales , Calbindina 1/metabolismo , Calcio/metabolismo , Calcio/toxicidad , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Evaluación Preclínica de Medicamentos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Neuronas Motoras/patología , Oligomicinas/toxicidad , Estrés Oxidativo/fisiología , Parvalbúminas/metabolismo , Riluzol/farmacología , Rotenona/toxicidad , Sodio/metabolismo , Sodio/toxicidad , Veratridina/toxicidad
7.
J Proteome Res ; 15(1): 216-28, 2016 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-26616104

RESUMEN

Acid rain (AR) impacts forest health by leaching calcium (Ca) away from soils and plants. Ca is an essential element and participates in various plant physiological responses. In the present study, the protective role of exogenous Ca in alleviating AR stress in Liquidambar formosana Hance at the physiological and proteomic levels was examined. Our results showed that low Ca condition resulted in the chlorophyll content and photosynthesis decreasing significantly in L. formosana leaves; however, these effects could be reversed by high Ca supplementation. Further proteomic analyses successfully identified 81 differentially expressed proteins in AR-treated L. formosana under different Ca levels. In particular, some of the proteins are involved in primary metabolism, photosynthesis, energy production, antioxidant defense, transcription, and translation. Moreover, quantitative real time polymerase chain reaction (qRT-PCR) results indicated that low Ca significantly increased the expression level of the investigated Ca-related genes, which can be reversed by high Ca supplementation under AR stress. Further, Western blotting analysis revealed that exogenous Ca supply reduced AR damage by elevating the expression of proteins involved in the Calvin cycle, reactive oxygen species (ROS) scavenging system. These findings allowed us to better understand how woody plants respond to AR stress at various Ca levels and the protective role of exogenous Ca against AR stress in forest tree species.


Asunto(s)
Calcio/toxicidad , Liquidambar/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Lluvia Ácida , Expresión Génica , Liquidambar/efectos de los fármacos , Redes y Vías Metabólicas , Hojas de la Planta/efectos de los fármacos , Proteínas de Plantas/genética , Proteoma/genética , Proteómica , Estrés Fisiológico
8.
J Chin Med Assoc ; 77(3): 142-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24548377

RESUMEN

BACKGROUND: Ginsenoside Rg1 (Rg1) is believed to be one of the main active principles in ginseng, a traditional Chinese medicine extensively used to enhance stamina and deal with fatigue as well as physical stress. It has been reported that Rg1 performs multiple biological activities, including neuroprotective activity. In this study, we investigated the efficacy of ginsenoside Rg1 on ischemia-reperfusion injury in cultured hippocampal cells and also probed its possible mechanisms. METHODS: To establish a model of oxygen-glucose deprivation (OGD) and reperfusion, cultured hippocampal neurons were exposed to OGD for 2.5 hours, followed by a 24-hour reoxygenation. Cultured hippocampal neurons were randomly divided into control group, model group (vehicle), and ginsenoside Rg1 treatment groups (5µM, 20µM, 60µM). At 24 hours post-OGD, the intracellular free calcium concentration was detected using Furo-3/AM-loaded hippocampal neurons deprived of oxygen and glucose. Neuronal nitric oxide synthase (nNOS) activity was measured by chemical colorimetry. Cell apoptosis was evaluated by Hoechst staining, and the neuron viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: Excitotoxic neuronal injury of OGD was demonstrated by the increase of intracellular free calcium concentrations and elevated nNOS activity in the model group compared with the control group. The intracellular free calcium concentrations and the nNOS activity in the groups receiving intermediate and high dose of ginsenoside Rg1 were significantly lower than those of the control group (p < 0.05). In addition, intermediate and high dose of ginsenoside Rg1 administration could also attenuate the cell viability loss (p < 0.05) and cell apoptosis induced by OGD. CONCLUSION: Ginsenoside Rg1 has neuroprotective effect on ischemia-reperfusion injury in cultured hippocampal cells mediated by blocking calcium over-influx into neuronal cells and decreasing the nNOS activity after OGD exposure. We infer that ginsenoside Rg1 may serve as a potential therapeutic agent for cerebral ischemia injury.


Asunto(s)
Fármacos del Sistema Nervioso Central/farmacología , Ginsenósidos/farmacología , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Daño por Reperfusión/fisiopatología , Animales , Calcio/toxicidad , Células Cultivadas , Glucosa/metabolismo , Hipocampo/citología , Oxígeno/metabolismo , Ratas , Ratas Sprague-Dawley
9.
Cancer Biol Ther ; 13(3): 130-7, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22231407

RESUMEN

The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+) and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies.


Asunto(s)
Antineoplásicos/uso terapéutico , Calcio/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Quinazolinas/uso terapéutico , Tirfostinos/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Azoximetano , Calcio/farmacología , Calcio/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Suplementos Dietéticos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Quinazolinas/farmacología , Quinazolinas/toxicidad , Distribución Aleatoria , Carga Tumoral/efectos de los fármacos , Tirfostinos/farmacología , Tirfostinos/toxicidad
10.
J Ren Nutr ; 22(1): 186-90, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22200440

RESUMEN

Recent debates between 2 schools of thought on calcium mass balance in dialysis patients and its relevance to disease--one emphasizing external calcium mass balance, and the other, internal calcium redistribution--have created controversy. Due to decreased ability to excrete calcium and loss of endocrine function by the kidney, patients suffering from chronic kidney disease, particularly when requiring dialysis, demonstrate varying degrees of positive or negative calcium balance, vitamin D deficiency, and secondary hyperparathyroidism. Consequently, patients are prone to bone demineralization, with diminished bone strength, and are thus prone to fractures that substantially worsen morbid outcomes in this population. However, intra- and interdialytic positive calcium mass balance creates complications of a different kind, which include the occurrence of vascular and cardiac disease and reduced survival. This review aims to shed light on the mechanisms of and relationships between external calcium mass balance and internal calcium redistribution and their consequences. It also discusses the potential to improve current regimens by means of diffusive and convective calcium mass transfer for the achievement of neutral calcium mass balance.


Asunto(s)
Calcio/metabolismo , Calcio/toxicidad , Diálisis Renal , Uremia/metabolismo , Calcio/farmacocinética , Calcio de la Dieta , Cardiopatías/etiología , Humanos , Hiperparatiroidismo Secundario , Fósforo/metabolismo , Uremia/complicaciones , Enfermedades Vasculares/etiología , Deficiencia de Vitamina D
11.
Environ Toxicol Chem ; 30(12): 2868-73, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21953527

RESUMEN

Maple leaf disks were conditioned in a stream for three weeks and then aerated for 2 d in distilled water to induce fungal sporulation. The release of aquatic hyphomycete spores increased when the water was supplemented with low concentrations of Ca(2+) (5 µg/L), Zn(2+) (2.5 µg/L), Cu(2+) (0.5 µg/L), or Cd(2+) (0.125 µg/L). Higher supplement concentrations inhibited sporulation. Over the concentration range used, the sporulation response was generally best described by a quadratic regression, suggesting a biphasic or hormetic response. A similar pattern was found with the number of fungal species as the dependent variable. Anguillospora filiformis and Anguillospora longissima were generally least inhibited by metal supplements, and Ca(2+) was the least and Cd(2+) the most toxic metal. Combinations of metals had a more severe effect on fungal sporulation than predicted from addition of the effects of the metals in isolation. The biological significance of the hormetic response is unclear; however, acknowledging it is clearly relevant for establishing guidelines or recommendations in toxicology.


Asunto(s)
Metales/toxicidad , Hongos Mitospóricos/efectos de los fármacos , Ríos/microbiología , Contaminantes Químicos del Agua/toxicidad , Cadmio/toxicidad , Calcio/toxicidad , Cationes Bivalentes/toxicidad , Cobre/toxicidad , Hongos Mitospóricos/crecimiento & desarrollo , Ríos/química , Zinc/toxicidad
12.
Toxicol Mech Methods ; 20(6): 334-44, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20528255

RESUMEN

The present study was conducted to examine the safety of a novel plant-based calcium supplement, derived from marine algae and containing high levels of calcium, magnesium, and other bone supporting minerals (commercially known as AlgaeCal (AC)). The present study evaluated the broad-spectrum safety of AC using a variety of toxicological assays including acute oral, acute dermal, primary skin irritation, and primary eye irritation toxicity. Under the conditions of the study, the acute oral LD(50) of AC was found to be greater than 5000 mg/kg body weight in rats, while the single acute dermal LD(50) was greater than 2000 mg/kg body weight. The primary skin irritation index of AC was found to be 0.4 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score of AC was observed to be 13.7 and classified as mildly irritating to the eye. Furthermore, another independent set of studies was conducted to obtain preliminary data for the teratogenic effects of AC in pregnant rats likely to arise from repeated gestational exposure, via oral gavage, over a test period of implantation through gestation (gestation days 5-19). Under the conditions of this pilot study, the effect of daily administration of AC by oral gavage at dose levels of 0, 500, 2500, and 5000 mg/kg/day during gestation days 5-19 of a 21-day pregnancy has appeared to result in no adverse toxicological effects to the pregnant rat or its developing offspring. A slight, non-significant increase in the incidence of incomplete sterna ossification (5(th) center) was observed. Under the conditions of the study, a no-observed-adverse effect level (NOAEL) of 5000 mg/kg/day of AC during pregnancy of the rat was observed. Overall, no significant toxicities of AC were observed in these toxicity models. Therefore, the results from the current study demonstrate a broad-spectrum safety profile of AC.


Asunto(s)
Calcio/toxicidad , Seguridad de Productos para el Consumidor , Suplementos Dietéticos/toxicidad , Eucariontes/química , Pruebas de Toxicidad/métodos , Animales , Peso Corporal/efectos de los fármacos , Calcio/aislamiento & purificación , Ojo/efectos de los fármacos , Femenino , Masculino , Especificidad de Órganos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Conejos , Ratas , Ratas Sprague-Dawley , Reproducción/efectos de los fármacos , Piel/efectos de los fármacos , Pruebas de Toxicidad Aguda
13.
Carbohydr Res ; 345(9): 1174-9, 2010 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-20457449

RESUMEN

Rheology of Ca-pectate gels is widely studied, but the behaviour of pectate gels formed by Cu, Al and La is largely unknown. It is well known that gel strength increases with increasing Ca concentration, and it is hypothesised that this would also be the case for other cations. Pectins are a critical component of plant cell walls, imparting various physicochemical properties. Furthermore, the mechanism of metal toxicity in plants is hypothesised to be, in the short term, related to metal interactions with cell wall pectin. This study investigated the influence of Ca, Cu, Al and La ion concentrations at pH 4 on the storage modulus as a function of frequency for metal-pectin gels prepared from pectin (1%) with a degree of esterification of 30%. Gels were formed in situ over 6d in metal chloride solution adjusted daily to pH 4. Cation concentration was varied to develop a relationship between gel strength and cation concentration. At similar levels of cation saturation, gel strength increased in the order of La

Asunto(s)
Pared Celular/química , Pared Celular/efectos de los fármacos , Metales/farmacología , Pectinas/química , Células Vegetales , Aluminio/farmacología , Aluminio/toxicidad , Calcio/farmacología , Calcio/toxicidad , Cobre/farmacología , Cobre/toxicidad , Relación Dosis-Respuesta a Droga , Geles , Concentración de Iones de Hidrógeno , Lantano/farmacología , Lantano/toxicidad , Metales/toxicidad , Concentración Osmolar , Plantas/efectos de los fármacos , Reología , Suelo , Soluciones
14.
Appl Environ Microbiol ; 76(12): 4019-26, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20435777

RESUMEN

Lotus species are forage legumes with potential as pastures in low-fertility and environmentally constrained soils, owing to their high persistence and yield under those conditions. The aim of this work was the characterization of phenetic and genetic diversity of salt-tolerant bacteria able to establish efficient symbiosis with Lotus spp. A total of 180 isolates able to nodulate Lotus corniculatus and Lotus tenuis from two locations in Granada, Spain, were characterized. Molecular identification of the isolates was performed by repetitive extragenic palindromic PCR (REP-PCR) and 16S rRNA, atpD, and recA gene sequence analyses, showing the presence of bacteria related to different species of the genus Mesorhizobium: Mesorhizobium tarimense/Mesorhizobium tianshanense, Mesorhizobium chacoense/Mesorhizobium albiziae, and the recently described species, Mesorhizobium alhagi. No Mesorhizobium loti-like bacteria were found, although most isolates carried nodC and nifH symbiotic genes closely related to those of M. loti, considered the type species of bacteria nodulating Lotus, and other Lotus rhizobia. A significant portion of the isolates showed both high salt tolerance and good symbiotic performance with L. corniculatus, and many behaved like salt-dependent bacteria, showing faster growth and better symbiotic performance when media were supplemented with Na or Ca salts.


Asunto(s)
Alphaproteobacteria/clasificación , Alphaproteobacteria/aislamiento & purificación , Lotus/microbiología , Raíces de Plantas/microbiología , Microbiología del Suelo , Alphaproteobacteria/efectos de los fármacos , Alphaproteobacteria/genética , Proteínas Bacterianas/genética , Calcio/toxicidad , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Datos de Secuencia Molecular , N-Acetilglucosaminiltransferasas/genética , Oxidorreductasas/genética , Filogenia , ARN Ribosómico 16S/genética , Rec A Recombinasas/genética , Sales (Química)/toxicidad , Análisis de Secuencia de ADN , Sodio/toxicidad , España
15.
Med Hypotheses ; 67(5): 1223-5, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16790324

RESUMEN

Alzheimer's disease is the most common form of dementia. Many risk factors have been defined in the literature, and the roles of environmental factors, nutrition, some vitamins and trace elements have been investigated. The role of magnesium (Mg) in dementia and other degenerative disorders has been the focus of increased attention in recent years. Concentration of Mg affects many biochemical mechanisms, which consist of N-methyl d-aspartate (NMDA) receptor response to excitatory amino acids, stability and viscosity of the cell membrane and toxic effects of calcium. Mg usage with drugs like memantine, which has an influence via Mg, can be useful in dementia treatment. According to the results of these studies, Mg support can facilitate learning and result in improvement in other symptoms. Memantine use has shown some benefit in moderate-to-severe Alzheimer's disease or for vascular dementia. Mg in the treatment of dementia facilitates learning and contributes to improvement in other symptoms; used in conjunction with memantine it may serve to increase memantine's symptomatic and neuroprotective effects, via its influence on NMDARs.


Asunto(s)
Demencia/tratamiento farmacológico , Magnesio/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/etiología , Autopsia , Calcio/toxicidad , Demencia/etiología , Suplementos Dietéticos , Sinergismo Farmacológico , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Humanos , Magnesio/metabolismo , Deficiencia de Magnesio/complicaciones , Memantina/uso terapéutico
16.
Rev. toxicol ; 19(1): 35-40, ene.-abr. 2002. tab
Artículo en Es | IBECS | ID: ibc-19194

RESUMEN

El calcio y el magnesio constituyen dos cationes esenciales para el organismo humano, los cuales se adquieren fundamentalmente a través de la dieta, pero en ocasiones se hace necesario su suplementación. El objetivo de este estudio es la evaluación de los posibles efectos tóxicos preclínicos de un suplemento oral de calcio y magnesio, el Calcidol. Se determinó la toxicidad aguda a través del ensayo límite a la dosis de 2000 mg/kg en ratas Wistar (Cenp:WIST) de ambos sexos, la irritación de la mucosa oral en hámsters Sirios Dorados machos (provenientes de CENPALAB, Cuba) mediante un ensayo agudo y a dosis repetidas y la toxicidad subcrónica oral en ratas Wistar de ambos sexos durante un período de 90 días con la administración de tres dosis (1280, 2560 y 5000 mg/kg/día). De modo general la administración aguda de las tabletas de Calcidol no provocó mortalidad ni manifestaciones tóxicas, resultando no irritante en la mucosa oral de hámster con un índice de irritación de 0,66 para el ensayo agudo y de 0,34 para el ensayo a dosis repetidas. En el ensayo de toxicidad subcrónica la mayor dosis administrada (5000 mg/kg/día) no produjo efectos tóxicos significativos reflejándose un comportamiento normal de ganancia de peso, consumo de alimentos y ausencia de signos tóxicos y mortalidad atribuible a la sustancia de prueba. Por otra parte se observó un aumento del pH urinario y una hipercelularidad fisiológica del tiroides, además de alteraciones histopatológicas a nivel de riñón las cuales constituyen una alerta para mantener una especial vigilancia sobre estos órganos diana en estudios posteriores (AU)


Asunto(s)
Animales , Femenino , Masculino , Ratas , Suplementos Dietéticos/toxicidad , Calcio/toxicidad , Magnesio/toxicidad , Administración Oral , Calcio/administración & dosificación , Calcio/orina , Magnesio/administración & dosificación , Magnesio/orina , Ratas Wistar , Mucosa Bucal , Concentración de Iones de Hidrógeno
17.
Rev. toxicol ; 19(1): 41-45, ene.-abr. 2002.
Artículo en Es | IBECS | ID: ibc-19195

RESUMEN

Las sales de calcio y magnesio son utilizadas como suplementos nutricionales obtenidas a partir de fuentes naturales dentro de las cuales se encuentra la dolomita, la cual es un mineral formado por un complejo doble de carbonato de calcio y magnesio. En la formulación de suplementos nutricionales a partir de la dolomita y en la búsqueda de una mayor biodisponibilidad, se obtuvo una materia prima en forma de citrato de calcio y magnesio a partir de la dolomita, la cual fue utilizada para la fabricación de las tabletas masticables de Acimín. El objetivo de nuestro estudio se centró en la evaluación toxicológica preclínica de estas tabletas, para lo cual se realizó un ensayo de toxicidad aguda oral en ratas Wistar de ambos sexos administrando la dosis de 2000 mg/kg, un ensayo de irritación de mucosa oral a dosis repetidas en hámsters Sirios Dorados hembras y un ensayo de irritacion de mucosa gástrica en ratas istar machos (250 - 300 g), aplicando las dosis de 2000, 1000 y 500 mg/kg. Como resultado se obtuvo que las tabletas de Acimín no poseen toxicidad significativa en el ensayo de toxicidad aguda oral (DL50>2000 mg/kg), no son irritantes de la mucosa oral (índice de irritacion de 0) y producen acidez e irritación sobre la mucosa gástrica a la dosis de 2000 mg/kg (AU)


Asunto(s)
Animales , Femenino , Masculino , Ratas , Suplementos Dietéticos/toxicidad , Calcio/toxicidad , Magnesio/toxicidad , Calcio/administración & dosificación , Magnesio/administración & dosificación , Disponibilidad Biológica , Comprimidos/toxicidad , Diseño de Fármacos , Mucosa Bucal , Determinación de la Acidez Gástrica , Ratas Wistar
18.
Vopr Pitan ; 70(1): 41-4, 2001.
Artículo en Ruso | MEDLINE | ID: mdl-11338347

RESUMEN

Selectivity of polyuronide sequestrants (pectate, alginates of various uronide composition) in respect to Sr2+ and Ca2+ ions has been evaluated in terms of thermodynamic affinity. It is suggested that there is no point in the use of pectate as a Sr(2+)-binding agent because at initial stages of reaction it reveals higher affinity to Ca2+ ions in comparison to Sr2+ ions. Contrary to pectate, alginates under similar conditions have higher affinity to Sr2+ ions. It is shown that these ions are bound only by blocks of L-guluronic acid residues in alginate macromolecules. The results obtained lend support to the advisability of the use of alginate preparations with the high content of L-guluronic acid residues for the excretion of Sr2+ ions from human body.


Asunto(s)
Calcio/toxicidad , Quelantes , Metales Alcalinotérreos/toxicidad , Estroncio/toxicidad , Termodinámica , Ácidos Urónicos , Alginatos , Calcio/metabolismo , Humanos , Ligandos , Sustancias Macromoleculares , Metales Alcalinotérreos/metabolismo , Modelos Teóricos , Pectinas , Espectrofotometría , Estroncio/metabolismo , Xenobióticos/toxicidad
19.
J Ethnopharmacol ; 55(2): 113-8, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9032623

RESUMEN

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Ajo/metabolismo , Atrios Cardíacos/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Plantas Medicinales , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/toxicidad , Animales , Calcio/toxicidad , Agonistas de los Canales de Calcio/toxicidad , Diálisis , Diltiazem/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Sinergismo Farmacológico , Atrios Cardíacos/metabolismo , Masculino , Nifedipino/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Verapamilo/farmacología
20.
Arch Environ Contam Toxicol ; 19(3): 457-63, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2353844

RESUMEN

In areas impacted by acid precipitation, water chemistry of acidic ponds and streams often changes, resulting in increased mobilization of aluminum and decreased concentration of calcium carbonate. Aluminum binds with phosphorus and inhibits its uptake by organisms. Thus, invertebrate food organisms used by waterfowl may have inadequate Ca and P or elevated Al for normal growth and development. Acid rain and its effects may be one of the factors negatively impacting American black ducks (Anas rubripes) in eastern North America. One-day old mallards (A. platyrhynchos) and black ducks were placed on one of three Ca:P regimens: low:low (LL), normal:normal (NN), and low:high (LH) with each regimen divided further into three or four Al levels for 10 weeks. Forty-five % of the black ducks died on nine different diets whereas only 28% of the mallards died on three different diets. Mortality was significantly related to diet in both species. Growth rates for body weight, culmens, wings, and tarsi of both species on control diets exceeded those on many treatment diets but the differences were less apparent for mallards than for black ducks. Differences among treatments were due to both Ca:P and Al levels.


Asunto(s)
Lluvia Ácida/efectos adversos , Aluminio/toxicidad , Calcio/toxicidad , Patos/fisiología , Crecimiento/efectos de los fármacos , Fósforo/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Dieta , Análisis de los Alimentos
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