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 PopulaçãoRESUMO
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 At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate.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/terapiaRESUMO
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 quimicamenteRESUMO
In order to verify the existence of a blood-thymus barrier to circulating macromolecules, the permeability of the vessels of the thymus was analyzed in young adult mice using electron opaque tracers of different molecular dimensions (horseradish peroxidase, cytochrome c, catalase, ferritin, colloidal lanthanum). Results show that although blood-borne macromolecules do penetrate the thymus, their parenchyma] distribution is limited to the medulla of the lobe by several factors: (a) the differential permeability of the various segments of the vascular tree; (b) the spatial segregation of these segments within the lobe; (c) the strategic location of parenchymal macrophages along the vessels. The cortex is exclusively supplied by capillaries, which have impermeable endothelial junctions. Although a small amount of tracer is transported by plasmalemmal vesicles through the capillary endothelium, this tracer is promptly sequestrated by macrophages stretched out in a continuous row along the cortical capillaries and it does not reach the intercellular clefts between cortical lymphocytes and reticular cells. The medulla contains all the leaky vessels, namely postcapillary venules and arterioles. Across the walls of the venules, large quantities of all injected tracers escape through the clefts between migrating lymphocytes and endothelial cells; also the arterioles have a small number of endothelial junctions which are permeable to peroxidase, but do not allow passage of tracers of higher molecular weight. The tracers released by the leaky vessels penetrate the intercellular clefts of the medulla, but they never reach the cortical parenchyma, even at long time intervals after the injection. Therefore, a blood-thymus barrier to circulating macromolecules does exist, but is limited to the cortex. Medullary lymphocytes are freely exposed to blood-borne substances.
Assuntos
Permeabilidade Capilar , Timo/irrigação sanguínea , Animais , Capilares/citologia , Catalase/sangue , Citocromos/sangue , Células Epiteliais , Feminino , Ferritinas/sangue , Junções Intercelulares , Lantânio/sangue , Substâncias Macromoleculares/sangue , Masculino , Camundongos , Microscopia Eletrônica , Peroxidases/sangue , Plantas Comestíveis/enzimologia , Coloração e RotulagemRESUMO
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 terapêuticoRESUMO
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/sangueRESUMO
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/metabolismoRESUMO
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/sangueRESUMO
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 GlaRESUMO
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 TratamentoRESUMO
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 & dosagemRESUMO
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 fármacosRESUMO
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 WistarRESUMO
BACKGROUND/AIMS: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. METHODS: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. RESULTS: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. CONCLUSION: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.
Assuntos
Carbonato de Cálcio/uso terapêutico , Lantânio/uso terapêutico , Fosfatos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Feminino , Humanos , Lantânio/efeitos adversos , Lantânio/sangue , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Vitamina D/sangueRESUMO
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 TempoRESUMO
To investigate the interactions between the systems that contribute to acid-base homeostasis after severe exercise, we studied the effects of carbonic anhydrase inhibition on exchange of strong ions and CO2 in six subjects after 30 s of maximal isokinetic cycling exercise. Each subject exercised on two randomly assigned occasions, a control (CON) condition and 30 min after intravenous injection of 1,000 mg acetazolamide (ACZ) to inhibit blood carbonic anhydrase activity. Leg muscle power output was similar in the two conditions; peak O2 uptake (VO2) after exercise was lower in ACZ (2,119 +/- 274 ml/min) than in CON (2,687 +/- 113, P less than 0.05); peak CO2 production (VCO2) was also lower (2,197 +/- 241 in ACZ vs. 3,237 +/- 87 in CON, P less than 0.05) and was accompanied by an increase in the recovery half-time from 1.7 min in CON to 2.3 min in ACZ. Whereas end-tidal PCO2 was lower in ACZ than in CON, arterial PCO2 (PaCO2) was higher, and a large negative end-tidal-to-arterial difference (less than or equal to 20 Torr) was present in ACZ on recovery. In ACZ, postexercise increases in arterial plasma [Na+] and [K+] were greater but [La-] was lower. Arteriovenous differences across the forearm showed a greater uptake of La- and Cl- in CON than in ACZ. Carbonic anhydrase inhibition with ACZ, in addition to impairing equilibration of the CO2 system to the acid-base challenge of exercise, was accompanied by changes in equilibration of strong inorganic ions. A lowered plasma [La-] was not accompanied by greater uptake of La- by inactive muscle.
Assuntos
Acetazolamida/farmacologia , Equilíbrio Ácido-Base/efeitos dos fármacos , Troca Gasosa Pulmonar/efeitos dos fármacos , Equilíbrio Ácido-Base/fisiologia , Adulto , Bicarbonatos/sangue , Dióxido de Carbono , Exercício Físico/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Lantânio/sangue , Masculino , Volume Plasmático/fisiologia , Potássio/sangue , Troca Gasosa Pulmonar/fisiologia , Respiração/efeitos dos fármacos , Respiração/fisiologia , Sódio/sangueRESUMO
We have examined the effects of pentoxifylline, a drug used to improve peripheral blood flow in patients with chronic vascular disorders, on shear-induced Ca2+ entry and Ca2+-dependent protein crosslinking in the erythrocyte. Cells were washed in isosmotic bicarbonate buffer, pH 7.5, and brought to a 20% suspension. 5 ml samples were sheared by swirling them for seconds; 45Ca2+ uptake, activation of Ca2+-dependent transglutaminase, and products of the crosslinking reaction were measured. A 5 second shear promoted 45Ca2+ entry, activation of Ca2+-dependent transglutaminase and crosslinking of proteins in the membrane-cytoskeletal fraction. Pentoxifylline, a drug that promotes erythrocyte deformability, diminished Ca2+ entry and inhibited activation of Ca2+-dependent transglutaminase, and had a prophylactic role on the effects of Ca2+ entry due to shear. Incubation of cells with 2.5 mM pentoxifylline before swirling minimized the effects of shear on 45Ca2+ entry, Ca2+-dependent transglutaminase and crosslinking of proteins. This study indicates that pentoxifylline promotes erythrocyte flexibility by minimizing shear-induced Ca2+ entry and Ca2+-dependent crosslinking.
Assuntos
Cálcio/sangue , Eritrócitos/enzimologia , Pentoxifilina/farmacologia , Teobromina/análogos & derivados , Transglutaminases/análise , Animais , Radioisótopos de Cálcio , Eletroforese em Gel de Poliacrilamida , Membrana Eritrocítica/metabolismo , Hemólise/efeitos dos fármacos , Lantânio/sangue , Masculino , Ratos , Ratos EndogâmicosRESUMO
140La accumulations in 20 tissues and tissue products of laying Japanese quail 1, 6 and 18 hr. after an intravenous dose of 15 mumol. La/100 g. body weight were greatest in the liver (43.1% at 18 hr.) and the growing oocytes (8.19% at 18 hr.). 47Ca accumulations 6 hr. after intravenous injection as compared with 140La levels were: shell 87.7% Ca, 0.0028% La; liver 0.110% Ca, 38.5% La; oocytes 0.852% Ca, 6.50% La. La3+ administered with the 47Ca did not alter the 47Ca levels. Deposition in eggs laid over an 8-day period was: 47Ca, shells 95.7%, maximum 77.6% on day 1; 140La, yolks 25.3%, maximum 8.35% on day 4.
Assuntos
Cálcio/metabolismo , Coturnix/metabolismo , Ovos/análise , Lantânio/metabolismo , Codorniz/metabolismo , Animais , Cálcio/sangue , Feminino , Lantânio/sangueRESUMO
Inductively coupled plasma mass spectrometry (ICP-MS), highly sensitive inorgnic analytic technique, fits to determine ultra-trace rare-earth elements in human plasma. Under the optimized conditions detection limits for 15 rare-earth elements are in the range of 0.7 (for Eu)-5.4 (for Gd) ng.L-1. Indium as an internal standard element is used to compensate for matrix suppression effect and sensitivity drift. Three kinds of preparation methods, diluted with 1% HNO3, digested with HNO3-H2O2 and with HNO3-HClO4, are checked and compared, and the former is the simplest way to be measured. The samples diluted with 1% HNO3, stored in 4 degrees C, are very steady for 16 days. With the method, 11 healthy plasma samples in Changchun area of China are analysed.
Assuntos
Espectrometria de Massas/métodos , Metais Terras Raras/sangue , Európio/sangue , Gadolínio/sangue , Lantânio/sangue , Espectrofotometria Atômica/métodosRESUMO
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.