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1.
Int J Nanomedicine ; 15: 3415-3431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523341

RESUMO

PURPOSE: Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in catalytic and photoelectric applications, but the reproductive toxicity is still unclear. This study evaluated the reproductive toxicity of two different-sized La2O3 particles in the testes. MATERIALS AND METHODS: Fifty Kunming mice were randomly divided into five groups. Mice were treated with La2O3 NPs by repeated intragastric administration for 90 days (control, nano-sized with 5, 10, 50 mg/kg BW and micro-sized with 50 mg/kg BW). Mice in the control group were treated with de-ionised water without La2O3 NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated. RESULTS: The body weight of mice treated with La2O3 NPs or not had no difference; sperm parameters and histological assessment showed that La2O3 NPs could induce reproductive toxicity in the testicle. Serum testosterone and gonadotropin-releasing hormone (GnRH) in the NH (nano-sized with 50 mg/kg BW) group were markedly decreased relative to control group, and an increase of luteinizing hormone (LH) in NH group was detected . Additionally, transmission electron microscopy revealed that the ultrastructural abnormalities induced by La2O3 NPs were more severe than La2O3 MPs in the testes. Furthermore, La2O3 NPs treatment inhibited the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm into the nucleus as well as the expression of downstream genes NAD(P)H quinone oxidoreductase1 (NQO1), hemeoxygenase 1 (HO-1) and (glutathione peroxidase) GSH-Px, thus abrogating Nrf-2-mediated defense mechanisms against oxidative stress. CONCLUSIONS: The results of this study demonstrated that La2O3 NPs improved the spermatogenesis defects in mice. La2O3 NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.


Assuntos
Elementos de Resposta Antioxidante/genética , Lantânio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas/toxicidade , Óxidos/toxicidade , Reprodução/efeitos dos fármacos , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Inflamação/patologia , Lantânio/sangue , Masculino , Camundongos , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Óxidos/sangue , Transdução de Sinais/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Testículo/ultraestrutura , Testosterona/biossíntese , Testosterona/metabolismo
2.
Neurotoxicol Teratol ; 77: 106854, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31891752

RESUMO

The increasing use of rare-earth elements in various fields has raised concern from public heath perspective regarding their accumulation in human body. Long-term exposure to lanthanum, one of the frequently used rare-earth elements in biomedicine and agriculture, has been previously shown to exert neurotoxicity during development in rats; however, the effects of short-term exposure to lanthanum during gestation on neurobehavioral development in rat offspring is still not clear. The purpose of this study is to investigate the effects of intrauterine exposure to lanthanum on neurobehavioral development in rat offspring. Dams were orally exposed to 0, 2, 20, & 60 mg/kg BW of lanthanum nitrate from gestation day 7 to day 16. Morris water maze test, hindlimb strength test, nociceptive perception test, and grip strength test were conducted during postnatal day 61 to 66 in rat offspring. Blood lanthanum concentration and plasma neurotransmitters were measured after sacrifice. The results showed that intrauterine exposure to lanthanum nitrate significantly impaired memory and spatial learning in Morris water maze test. Lanthanum treatment dose-dependently increased blood lanthanum concentration in dams and pups. Lanthanum treatment significantly decreased hindlimb and grip strength and increased delay time in nociceptive response. Plasma neurotransmitter results showed that lanthanum treatment significantly decreased the level of acetylcholine and serotonin while increased the level of glutamate in rat offspring. These results suggest that short-term in utero exposure to lanthanum has potential adverse effects on neurodevelopment in rat offspring.


Assuntos
Força da Mão/fisiologia , Lantânio/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacos , Força Muscular/fisiologia , Óxidos/efeitos adversos , Percepção da Dor/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Acetilcolina/sangue , Animais , Relação Dose-Resposta a Droga , Feminino , Ácido Glutâmico/sangue , Membro Posterior/fisiopatologia , Lantânio/sangue , Masculino , Óxidos/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Serotonina/sangue
3.
Intern Med ; 57(24): 3589-3591, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30146573

RESUMO

Tumoral calcinosis (TC) is a rare benign but aggressive disorder with variable response rates and high recurrence rates despite medical or surgical treatments. We herein report a case of a 28-year-old woman with underlying systemic lupus erythematosus (SLE) who developed diffuse tumoral calcinosis that was successfully treated by lanthanum carbonate. The formation of tumoral calcinosis depends on the supersaturation of calcium and phosphate. Lanthanum carbonate not only has an excellent phosphate-lowering ability but also low gastro-intestinal calcium absorption. It can be considered an effective alternative treatment for tumoral calcinosis if surgical treatment is not feasible.


Assuntos
Calcinose/tratamento farmacológico , Lantânio/uso terapêutico , Adulto , Calcinose/sangue , Calcinose/complicações , Calcinose/dietoterapia , Cálcio/sangue , Feminino , Absorção Gastrointestinal , Humanos , Lantânio/sangue , Lúpus Eritematoso Sistêmico/complicações , Fosfatos/sangue , Resultado do Tratamento
4.
Artigo em Chinês | MEDLINE | ID: mdl-29699006

RESUMO

Objective: To investigate the levels of lanthanum, cerium, praseodymium, and neodymium in the blood, urine, and hair samples from residents in the rare earth mining area of a city in China, and to provide a scientific basis for the control of rare earth pollution and the protection of population health. Methods: A total of 147 residents who had lived in the rare earth mining area of a city for a long time were selected as the exposure group, and 108 residents in Guyang County of this city who lived 91 km away from the rare earth mining area were selected as the control group. Blood, urine, and hair samples were collected from the residents in both groups. Inductively coupled plasma mass spectrometry was used to determine the content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair samples. Results: In the exposure group, the median levels of lanthanum, cerium, praseodymium, and neodymium were 0.854, 1.724, 0.132, and 0.839 µg/L, respectively, in blood samples, 0.420, 0.920, 0.055, and 0.337 µg/L, respectively, in urine samples, and 0.052, 0.106, 0.012, and 0.045 µg/g, respectively, in hair samples. The exposure group had significantly higher levels of the four rare earth elements in blood, urine, and hair samples than the control group (P<0.01) . Conclusion: The residents in the rare earth mining area of this city have higher content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair than those in the non-mining area; the content of cerium is highest, followed by lanthanum, neodymium, and praseodymium.


Assuntos
Cabelo/química , Lantânio/sangue , Lantânio/urina , Metais Terras Raras/sangue , Metais Terras Raras/urina , Mineração , China , Exposição Ambiental , Humanos , Vigilância da População
5.
Microscopy (Oxf) ; 66(5): 366-370, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016922

RESUMO

Triolein emulsion has been known to increase vascular permeability in the brain when it is infused into the carotid artery. The purpose of this study was to identify the morphologic mechanism of increased vascular permeability in brain induced by infusion of emulsified triolein into the carotid artery by transmission electron microscopy (TEM). Triolein emulsion was infused into the carotid artery of rats. TEM using lanthanum tracer was used to evaluate morphologic changes in endothelium with a focus on transcytotic vesicles and tight junction opening. The treat group showed multiple transcytotic vesicles containing lanthanum tracer within endothelium on TEM. TEM also revealed that lanthanum tracer entered neural interstitium through tight junctions between capillary endothelial cells infrequently in the treat group. No evidence of transcytotic vesicles containing lanthanum tracer or lanthanum leakage through tight junctions was observed in the control group. Transcytosis and the opening of tight junctions appears the pathway for vascular permeability enhancement by triolein. This result could be utilized in studies on the blood-brain barrier and by those searching for chemotherapeutic methods that deliver anti-tumor agents to normally drug inaccessible organs.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Trioleína/administração & dosagem , Animais , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/ultraestrutura , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/ultraestrutura , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Endotélio/efeitos dos fármacos , Infusões Intra-Arteriais , Lantânio/administração & dosagem , Lantânio/sangue , Microscopia Eletrônica de Transmissão/métodos , Ratos , Transcitose/efeitos dos fármacos
6.
Contrib Nephrol ; 185: 42-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26023014

RESUMO

In end-stage renal disease patients, various abnormalities of bone mineral metabolism adversely affect mortality. Hyperphosphatemia is known to adversely affect mortality and quality of life in chronic kidney disease patients and has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. Thus, hyperphosphatemia is the main treatment target indicated in several guidelines for chronic kidney disease-mineral and bone disorder treatment. Phosphate binders are typically required for the management of hyperphosphatemia because dietary phosphorus restriction and phosphorus removal by hemodialysis alone are insufficient. We are able to prescribe five phosphate binders (calcium carbonate, sevelamer HCl, lanthanum carbonate (LaC), bixalomer, and ferric citrate) to Japanese hemodialysis patients. LaC is the most powerful noncalcium-containing phosphate binder for the treatment of hyperphosphatemia. In this chapter, we discuss the efficacy and safety of LaC, the safety of which has been under debate. In particular, we consider its toxic effects on the skeletal system. LaC is effective for hyperphosphatemia treatment in end-stage renal failure patients. It has been shown to be able to decrease serum fibroblast growth factor-23 levels. This result suggests that it may have beneficial effects on the cardiovascular system in patients undergoing renal replacement therapy. However, the effects of LaC remain obscure. Further investigations are required. No negative effects of LaC on bone metabolism or bone morphometry have been reported, but long-term clinical data are needed.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/terapia , Lantânio/uso terapêutico , Osso e Ossos/patologia , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/etiologia , Falência Renal Crônica/complicações , Lantânio/efeitos adversos , Lantânio/sangue , Fosfatos/sangue , Diálise Renal , Fatores de Tempo
7.
J Ren Nutr ; 25(2): 242-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25556148

RESUMO

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL.


Assuntos
Carbonato de Cálcio/farmacologia , Lantânio/farmacologia , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangue , Diálise Renal , Insuficiência Renal Crônica/sangue , Carbonato de Cálcio/sangue , Feminino , Humanos , Lantânio/sangue , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/efeitos dos fármacos , Fosfatos , Insuficiência Renal Crônica/terapia
8.
Physiol Res ; 63(4): 457-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24702492

RESUMO

Time delay in the mediation of ventilation (V(.)E) by arterial CO(2) pressure (PaCO(2)) was studied during recovery from short impulse-like exercises with different work loads of recovery. Subjects performed two tests including 10-s impulse like exercise with work load of 200 watts and 15-min recovery with 25 watts in test one and 50 watts in test two. V(.)E, end tidal CO(2) pressure (PETCO(2)) and heart rate (HR) were measured continuously during rest, warming up, exercise and recovery. PaCO(2) was estimated from PETCO(2) and tidal volume (V(T)). Results showed that predicted arterial CO(2) pressure (PaCO(2 pre)) increased during recovery in both tests. In both tests, V(.)E increased and peaked at the end of exercise. V(.)E decreased in the first few seconds of recovery but started to increase again. The highest correlation coefficient between PaCO(2 pre) and V(.)E was obtained in the time delay of 7 s (r=0.854) in test one and in time delays of 6 s (r=0.451) and 31 s (r=0.567) in test two. HR was significantly higher in test two than in test one. These results indicate that PaCO(2 pre) drives V(.)E with a time delay and that higher work intensity induces a shorter time delay.


Assuntos
Dióxido de Carbono/sangue , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Mecânica Respiratória/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Lantânio/sangue , Masculino , Adulto Jovem
9.
Curr Med Res Opin ; 30(1): 99-108, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24063635

RESUMO

OBJECTIVE: To evaluate the efficacy and tolerability of lanthanum carbonate (LC) in the treatment of hyperphosphatemia in dialysis patients. METHOD: Multiple databases were used to recruit the published clinical randomized controlled trials (RCTs) comparing LC with placebo for hyperphosphatemia in dialysis patients from inception to March 2013. Results were expressed using standardized mean difference (SMD) for continuous variables and pooled odd ratios (OR) for dichotomous outcomes. Study quality was assessed according to Cochrane Handbook 5.1 guidelines and statistical analysis was performed using RevMan 5.2 software. RESULTS: A total of 950 patients in seven placebo-controlled RCTs were included. Results showed that LC could effectively controlled hyperphosphatemia compared with placebo (SMD -1.06, 95% CI -1.27- -0.86, P < 0.00001). The proportion of subjects reaching the target in the LC group was higher than that in the placebo group (OR 6.88, 95% CI 4.39-10.78, P < 0.00001). LC-treated patients showed less change in serum PTH and Ca × Pi product from baseline compared to the placebo group (SMD -0.21, 95% CI -0.48-0.06, P = 0.007; SMD -0.90, 95% CI -1.13- -0.66, P < 0.00001, respectively). LC-treated patients experienced more side-effects, like vomiting and nausea, than controls (OR 3.10, 95% CI 1.35-7.08, P = 0.007; OR 2.74, 95% CI 1.22-6.19, P = 0.02, respectively). But overall, the incidence of drug-related adverse events was similar between placebo- and LC-treated patients (OR 1.21, 95% CI 0.66-2.22, P = 0.54). CONCLUSION: In the treatment of hyperphosphatemia in dialysis patients, LC is well tolerated and more effective than placebo during short-term trials. Furthermore, it helps to maintain PTH and Ca × Pi product levels within recommended ranges. LC is an ideal choice for second-line treatment of hyperphosphatemia after therapy failure or other contraindication for calcium agents. Its long-term security still needs further research.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Lantânio/uso terapêutico , Diálise Renal , Cálcio/sangue , Humanos , Hiperfosfatemia/sangue , Falência Renal Crônica/sangue , Lantânio/efeitos adversos , Lantânio/sangue , Fosfatos/sangue , Placebos/efeitos adversos , Placebos/uso terapêutico , Resultado do Tratamento
10.
Ren Fail ; 35(10): 1455-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23992043

RESUMO

AIM: To assess the effect and safety of lanthanum carbonate (LC) for hypophosphatemia in patients with end-stage renal disease (ESRD). METHODS: According to the collaborative review group search strategy, we searched MEDLINE (1996 to 2012.12); EBCO (1996 to 2012.12), and CNKI. We searched Chinese journals by hand. We conducted quality assessment and data extraction by two independent investigators. Meta-analysis was conducted by RevMan 5.0. Results were expressed as OR with 95% confidence interval for dichotomous outcomes and WMD with 95% confidence interval for continuous outcomes. RESULT: We identified 16 reports which might meet the inclusion criteria for our review. The meta-analysis showed that LC was superior to placebo in treating hypophosphatemia of end-stage renal disease patients (OR = 5.46, 95% CI: 2.37 to 2.61, p < 0.005) and as efficient as conventional therapies (WMD = -0.06, 95% CI: -0.27 to 0.15, p = 0.57). The incidence of all adverse events was similar between LC- and placebo-treated patients (OR = 1.16, 95% CI: 0.79 to 1.68, p = 0.45). CONCLUSION: Lanthanum carbonate is well effective and tolerated in treating hyperphosphatemia of ESRD patients. Lanthanum carbonate is not likely to cause hypercalcemia compared to calcium-based phosphate binders.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/complicações , Lantânio/uso terapêutico , Osso e Ossos/metabolismo , Cálcio/sangue , Humanos , Hiperfosfatemia/etiologia , Falência Renal Crônica/mortalidade , Lantânio/sangue , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Calcificação Vascular/induzido quimicamente
11.
J Phys Condens Matter ; 25(7): 076004, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23339833

RESUMO

Magnetic properties of basically antiferromagnetic La(0.23)Ca(0.77)MnO(3) particles with average sizes of 12 and 60 nm have been investigated in a wide range of magnetic fields and temperature. Particular attention has been paid to magnetization dynamics through measurements of the temperature dependence of ac-susceptibility at various frequencies, the temperature and field dependence of thermoremanent and isothermoremanent magnetization originating from nanoparticles shells, and the time decay of the remanent magnetization. Experimental results and their analysis reveal the major role in magnetic behaviour of investigated antiferromagnetic nanoparticles played by the glassy component, associated mainly with the formation of the collective state formed by ferromagnetic clusters in frustrated coordination at the surfaces of interacting antiferromagnetic nanoparticles. Magnetic behaviour of nanoparticles has been ascribed to a core-shell scenario. Magnetic transitions have been found to play an important role in determining the dynamic properties of the phase separated state of coexisting different magnetic phases.


Assuntos
Lantânio/sangue , Campos Magnéticos , Compostos de Manganês/química , Óxidos/química , Elétrons , Teste de Materiais
12.
Ann Clin Biochem ; 48(Pt 2): 178-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21367883

RESUMO

BACKGROUND: Lanthanum carbonate is used as a phosphate binder in patients with stage V chronic kidney disease (CKD). While well tolerated in clinical trials, with no toxicity reported as regards bone and liver metabolism, and cognitive function, concerns remain over possible toxicity. Published methods for the measurement of lanthanum ion in biological samples include aggressive and complicated sample preparation steps that are unsuitable for routine use. A simple method has been developed and validated for the measurement of serum lanthanum. METHOD: A ThermoFisher Scientific XSERIES-II inductively coupled plasma-mass spectrometer was used to monitor ¹³9La. Validation was undertaken using internal quality control solutions containing lanthanum ion (0.20, 0.70 and 4.00 µg/L). Lanthanum was measured in patients (number = 20) with CKD prescribed lanthanum carbonate (500-1500 mg/d) and patients undergoing haemodialysis not prescribed lanthanum carbonate (number = 20). RESULTS: Accuracy and imprecision were >95% and <5%, respectively. Calibration was linear (range 0.1-5 µg/L, R² = 0.99). The lower limit of quantification (LLoQ) was 0.1 µg/L lanthanum ion. In patients with CKD not prescribed lanthanum carbonate, serum lanthanum was below the LLoQ. Out of 20 CKD patients prescribed lanthanum carbonate, serum lanthanum was measurable in only 12 (range 0.11-0.60 µg/L lanthanum ion). There was no apparent relationship between dose and serum lanthanum in these patients. CONCLUSIONS: A lack of relationship between the dose of lanthanum carbonate and the serum lanthanum concentration may have been due to poor adherence to the treatment regimen. However the concentrations measured were close to the LLoQ.


Assuntos
Análise Química do Sangue/métodos , Lantânio/sangue , Espectrometria de Massas/métodos , Adulto , Idoso , Contaminação de Medicamentos , Feminino , Humanos , Nefropatias/tratamento farmacológico , Lantânio/uso terapêutico , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Diálise Renal , Reprodutibilidade dos Testes
13.
Clin Exp Nephrol ; 14(6): 589-97, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20814807

RESUMO

BACKGROUND: Lanthanum carbonate is a non-aluminum, non-calcium phosphate binder. Its efficacy and its safety profile up to 1 year have been reported in Japanese hemodialysis patients. METHODS: The present study was an extension of the earlier study. One hundred and forty-five patients were enrolled in the original 1 year observational Phase III study. After 1 year of treatment, 63 patients continued with further lanthanum treatment. Lanthanum carbonate was administered at 750-4,500 mg/day for up to 156 weeks (3 years). The reduction in serum phosphate was used to evaluate efficacy, and laboratory markers of bone turnover were monitored. RESULTS: The serum phosphate level was maintained at a significantly lower level (P < 0.05) than the baseline level during the 3-year study period. Most of the drug-related adverse events were mild and were mainly gastrointestinal disorders. The safety profile of lanthanum during 3 years of treatment was similar to that seen in the previous study. There were no clinically relevant changes in vital signs or the electrocardiogram. Bone turnover markers, such as osteocalcin, bone-specific alkaline phosphatase, and crosslinked N-telopeptide of type I collagen, showed no clinically relevant changes. CONCLUSION: Lanthanum therapy was able to reduce and maintain the serum phosphate level within the K/DOQI and JSDT guideline ranges in Japanese dialysis patients for 3 years.


Assuntos
Falência Renal Crônica/tratamento farmacológico , Lantânio/uso terapêutico , Diálise Renal , Idoso , Povo Asiático , Feminino , Humanos , Lantânio/efeitos adversos , Lantânio/sangue , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Resultado do Tratamento , Vitamina D/uso terapêutico
14.
Ther Apher Dial ; 14(1): 12-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20438515

RESUMO

Lanthanum carbonate is a non-calcium-based phosphate binder for hyperphosphatemia in patients with chronic kidney disease (CKD). The efficacy and safety of lanthanum carbonate (LaC) on hyperphosphatemia in patients has been well documented in clinical trials in Western countries and recent relatively short-term clinical trials in Japan. Evidence supporting its safety and efficacy in Japanese patients for longer-term treatment is now desired for clinical practice. A non-controlled, open-label, multicenter, one year study of LaC to assess safety and its effect on the levels of serum phosphate, serum calcium and parathyroid hormone was performed with Japanese dialysis patients. Lanthanum carbonate was administered to patients at variable doses for a period of 46-52 weeks. Evaluation of the safety and efficacy of LaC in reducing serum phosphate was performed, in addition to extensive and systematic monitoring of the laboratory parameters related to bone turnover and cardiac health. A significant reduction in the serum phosphate level was demonstrated throughout the treatment period (P < 0.05), without any increase in the frequency or severity of drug-related adverse events such as vomiting, nausea, and stomach discomfort. There was no clinically relevant change in vital signs, or electrocardiograms for a period. The profiles for parathyroid hormone, bone alkaline phosphates, and osteocalcin were stable in the patients concomitantly treated with vitamin D. This study provides further evidence that the administration of LaC over a period of one year is safe and effective for the reduction of serum phosphate levels in CKD patients undergoing hemodialysis.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/complicações , Lantânio/uso terapêutico , Diálise Renal , Dor Abdominal/induzido quimicamente , Adulto , Idoso , Cálcio/sangue , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/etiologia , Japão , Falência Renal Crônica/sangue , Lantânio/efeitos adversos , Lantânio/sangue , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Resultado do Tratamento , Vômito/induzido quimicamente
15.
Exp Biol Med (Maywood) ; 234(8): 908-17, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19546357

RESUMO

Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P < 0.01), respectively; reducing aortic mRNA level of OPN and Pit-1, by 55.8% (P < 0.01) and 38.8% (P < 0.05) and protein level of OPN and Pit-1, by 37.2% and 27.2% (both P < 0.01), respectively; and increasing carboxylated matrix Gla-protein (MGP) protein expression by 33.7% (P < 0.05), as compared with rats treated with vitamin D3 and nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.


Assuntos
Acetatos/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Calcinose/induzido quimicamente , Calcinose/prevenção & controle , Colecalciferol/farmacologia , Lantânio/farmacologia , Nicotina/efeitos adversos , Acetatos/sangue , Animais , Aorta/metabolismo , Calcinose/sangue , Cálcio/sangue , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lantânio/sangue , Masculino , Osteopontina/genética , Osteopontina/metabolismo , Fósforo/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismo , Proteína de Matriz Gla
16.
Kidney Int ; 75(4): 355-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19180150

RESUMO

Mineral metabolism in chronic kidney disease is attracting intense interest and unprecedented levels of research. The pharmaceutical industry has responded by developing various new agents. Bervoets et al. report the use of an unusual combination of basic-science techniques to increase understanding of the kinetics of one such agent--lanthanum carbonate--in the gastrointestinal tract and liver. However, do we need to answer more fundamental clinical questions before we can definitively identify the role of similar new and expensive drugs?


Assuntos
Falência Renal Crônica/tratamento farmacológico , Lantânio/farmacocinética , Trato Gastrointestinal/metabolismo , Humanos , Falência Renal Crônica/mortalidade , Lantânio/sangue , Lantânio/uso terapêutico , Fígado/metabolismo , Pessoa de Meia-Idade , Minerais/metabolismo , Fosfatos/sangue
17.
Toxicol Sci ; 103(2): 354-61, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18319242

RESUMO

With their widespread application in industry, agriculture, medicine, and daily life, rare earth elements (REEs) are widely used in various fields and eventually accumulated in human body. Therefore, understanding the effects of REEs on health has become more and more important. In this work, the neurotoxicity of lanthanum (La) was evaluated. Wistar rats were exposed to lanthanum chloride through oral administration at 0, 0.1, 2, and 40 mg/kg doses from gestation day 0 through 6 months of age. Experiments were carried out to reveal the effects of La exposure on brain functions from four aspects including behavioral performance, [Ca2+](i) level and the activity of Ca2+-ATPase (adenosine triphosphatase) in hippocampal cells, oxidative stress, and Nissl staining. Adverse effects were observed in 2 and 40 mg/kg dose groups and increased with dose. Morris water maze test showed that La exposure at 2 and 40 mg/kg could significantly impair the behavioral performance. (The preference for the target quadrant decreased by 16.6% and 19.4% versus control, respectively.) The neurotoxicological consequences demonstrated that the alteration in homeostasis of [Ca2+](i)/Ca2+-ATPase (the ratio of [Ca2+](i) vs. Ca2+-ATPase activity increased by 44% in rats of 40 mg/kg group), the inhibition to activities of antioxidant enzymes, and the subsequent cell damage (18% and 23% cell loss in CA3 subregion of rats in 2 and 40 mg/kg group, respectively) might be involved in the neurological adverse effects of REEs exposure.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Lantânio/toxicidade , Exposição Materna/efeitos adversos , Síndromes Neurotóxicas/etiologia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Química Encefálica , ATPases Transportadoras de Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Feminino , Lantânio/sangue , Lantânio/farmacocinética , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Corpos de Nissl/efeitos dos fármacos , Corpos de Nissl/patologia , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Testes de Toxicidade
18.
Toxicol Lett ; 171(1-2): 69-77, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17570622

RESUMO

Lanthanum carbonate is a non-calcium-based oral phosphate binder for the control of hyperphosphataemia in patients with chronic kidney disease Stage 5. As part of its pre-clinical safety evaluation, studies were conducted in rats to determine the extent of absorption and routes of excretion. Following oral gavage of a single 1500 mg/kg dose, the peak plasma lanthanum concentration was 1.04+/-0.31 ng/mL, 8 h post-dose. Lanthanum was almost completely bound to plasma proteins (>99.7%). Within 24h of administration of a single oral dose, 97.8+/-2.84% of the lanthanum was recovered in the faeces of rats. Comparing plasma exposure after oral and intravenous administration of lanthanum yielded an absolute oral bioavailability of 0.0007%. Following intravenous administration of lanthanum chloride (0.3 mg/kg), 74.1+/-5.82% of the dose (96.9+/-0.50% of recovered lanthanum) was excreted in faeces in 42 days, and in bile-duct cannulated rats, 10.0+/-2.46% of the dose (85.6+/-2.97% of recovered lanthanum) was excreted in bile in 5 days. Renal excretion was negligible, with <2% of the intravenous dose recovered in urine. These studies demonstrate that lanthanum undergoes extremely low intestinal absorption and that absorbed drug is predominantly excreted in the bile.


Assuntos
Bile/metabolismo , Lantânio/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Cães , Avaliação Pré-Clínica de Medicamentos/métodos , Fezes/química , Feminino , Glicoproteínas/metabolismo , Humanos , Injeções Intravenosas , Intubação Gastrointestinal , Lantânio/administração & dosagem , Lantânio/sangue , Lantânio/farmacologia , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Camundongos , Ligação Proteica , Coelhos , Ratos , Ratos Sprague-Dawley , Albumina Sérica/metabolismo , Fatores Sexuais , Cloreto de Sódio/administração & dosagem
19.
Nephrol Dial Transplant ; 21(8): 2217-24, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16595583

RESUMO

BACKGROUND: Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma. METHODS: Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years). RESULTS: After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6 microg/g (P < 0.05). CONCLUSIONS: Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 microg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Ílio/química , Falência Renal Crônica/complicações , Lantânio/análise , Diálise Renal/efeitos adversos , Idoso , Fosfatase Alcalina/sangue , Biomarcadores , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Feminino , Seguimentos , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Lantânio/efeitos adversos , Lantânio/sangue , Lantânio/farmacocinética , Lantânio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/metabolismo , Fósforo/sangue , Resultado do Tratamento
20.
Bone ; 38(6): 803-10, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16412714

RESUMO

BACKGROUND: We have previously shown that administration of the new phosphate binder lanthanum (La) carbonate at high doses during 12 weeks induces a mineralization defect (MD) in chronic renal failure (CRF) rats most likely due to the powerful phosphate binding. In this study, we want to investigate the fate and possible biological activities of La once it is accumulated in bone. METHODS: CRF animals (5/6th nephrectomy) received La carbonate (2,000 mg/kg/day) via oral gavage for 2 or 6 weeks and were sacrificed immediately at the end of the treatment period and after a wash out period of 2 and 8 weeks. Bone histomorphometry and measurement of bone La content were performed. Control CRF animals received vehicle only. RESULTS: After 2 weeks of La treatment, 75% of the animals showed signs of MD compared to 14% in CRF controls despite similar bone La levels. Two weeks after arrest of La treatment, bone La levels remained unchanged, yet 87% showed normal bone histology. A similar evolution was noted in the animals treated for 6 weeks. Bone histology showed a reduction of number of animals with a MD from 62.5% at 6 weeks of La treatment to 20% and 28% 2 and 8 weeks after arrest of La treatment respectively. CONCLUSION: The phosphate-binder-induced MD may appear and disappear without any change in either the perimeter of active osteoblasts or in bone La levels. Bone histology in CRF animals normalized after arrest of the La administration, thereby presenting further arguments for the MD in La-treated animals to result from the high phosphate binding capacity of La rather than being the consequence of a direct effect of La on bone.


Assuntos
Densidade Óssea/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/patologia , Lantânio/farmacologia , Animais , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/sangue , Cálcio/urina , Lantânio/sangue , Masculino , Fosfatos/sangue , Fosfatos/urina , Ratos , Ratos Wistar
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