Lanthanum hydroxide inhibits CKD-induced vascular calcification by blocking HIF-1α signaling pathway / 中国药理学通报

Aim To investigate the therapeutic effect of lanthanum hydroxide on renal injury and vascular calcification in rats caused by chronic kidney disease (CKD) and the underlying mechanism. Methods A CKD model was constructed by adenine, and the rats were randomly divided into model group, lanthanum hydroxide low, medium and high dose groups, lanthanum carbonate group and calcium carbonate group. After eight weeks, serum phosphorus ( Pi ), calcium (Ca), serum creatinine ( Scr), blood urea nitrogen ( BUN ), parathyroid hormone ( PTH ), fibroblast growth factor 23 ( FGF23 ) and tartrate-resistant acid phosphatase 5b ( TARP-5b) levels were measured. Histopathological staining was used to assess the degree of calcification of blood vessels, and the expressions of smooth muscle protein 22α ( SM22α), Runt-related transcription factor 2 ( RUNX2 ), hypoxia inducible factor 1 ( HIF-1) pathway mRNA and protein expression in blood vessels were detected. Results Lanthanum hydroxide can significantly reduce the levels of Pi, Scr, BUN, PTH, FGF23 and TARP-5b in the serum of CKD rats, significantly reduce the calcium deposition of the thoracic aorta of CKD rats, the expression of BMP-2, VEGF in the cytoplasm, the expression of RUNX2, HIF-1α in the nucleus, and increase the mRNA and protein expression of SM22. Conclusion Lanthanum hydroxide can markedly improve hyperphosphatemia in CKD rats, and can improve vascular calcification in CKD rats by blocking HIF-1α signaling pathway.

The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9 / 中华劳动卫生职业病杂志

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

Determination of lanthanum in whole blood by microwave digestion-inductively coupled plasma optical emission spectrometry / 药学实践杂志

Objective To evaluate the transdermal safety of lanthanum (La) in sunscreen and jellyfish sting protective lotion, establish a microwave digestion-inductively coupled plasma opticalemission spectroscopy (ICP-OES) method for determination of lanthanum (La) in rat’s whole blood. Methods The whole blood samples were digested by microwave and analyzed by inductively coupled plasma emission spectrometer (ICP-OES). Using 333.749 nm as the analysis line, the content of La in rat whole blood was determined. Results The correlation linearity of the standard curve of this method was good (r>0.9994), the detection limit of the method was 0.0025 μg/ml, the limit of quantification was 0.0077 μg/ml, the precision was less than 3%, and the recovery rate was between 94.9% and 102.0%. Conclusion The ICP-OES method based on microwave digestion is stable and reliable, and can provide an important basis for the study of the transdermal safety of lanthanum.

Discussion on the Inhibitory Mechanism of Lanthanum Chloride on Vascular Smooth Muscle Cell Calcification Induced by High Phosphorus Based on NF-κB Signaling Pathway / 中国药房

OBJECTIVE：To discuss the inhibitory effect of lanthanum chloride on the calcification of vascular smooth muscle cells（VSMCs）induced by high phosphorus and its mechanism. METHODS ：On the basis of screening the action concentration and time of lanthanum chloride by MTT method ，human VSMCs were divided into control group （1 mmol/L phosphorus solution ）， lanthanum chloride high concentration control group （1 mmol/L phosphorus solution+ 60 μmol/L lanthanum chloride），model group （3 mmol/L phosphorus solution ），sodium chloride group （3 mmol/L phosphorus solution+ 180 μmol/L sodium chloride），nuclear factor κB（NF-κB）signaling pathway agonist+lanthanum chloride group （3 mmol/L phosphorus solution+ 1 μg/mL lipopolysaccharide+ 60 μmol/L lanthanum chloride），positive control group （3 mmol/L phosphorus solution+ 100 μmol/L sodium pyrophosphate），and lanthanum chloride low ，medium，and high concentration groups （3 mmol/L phosphorus solution+ 15，30，60 μmol/L lanthanum chloride）. Alizarin red S staining and Von Kossa staining were used to detect cell calcification in each group after treated with phosphorus solution for 6 d and relevant medicine for 2 d. Western blot assay was used to detect the protein expression of TNF-α receptor associated protein 6（TRAF6），nuclear factor κB inhibitor protein α（IκBα），NF-κB p65，bone morphogenetic protein 2 （BMP-2），smooth muscle 22 α（SM22α）and Runt related transcription factor 2（Runx2）. Real-time fluorescence quantitative polymerase chain reaction was used to detect mRNA expression of TRAF 6，IκBα，BMP-2，SM22α and Runx2. RESULTS ： Compared with control group ，no cell calcification was observed in the lanthanum chloride high concentration control group ，while obvious cell calcification and significant increase of OD value were observed in model group and sodium chloride group （P＜ 0.01）；protein and mRNA expression of TRAF 6 and BMP- 2 in cytoplasm as well as mRNA expression of Runx 2，protein expression of NF-κB p65 and Runx 2 in nucleus were significantly increased （P＜0.01）；protein and mRNA expression of IκBα and SM22α as well as protein expression of NF-κB p65 in cytoplasm were significantly decreased （P＜0.01）. Compared with model group，cell calcification was significantly improved in lanthanum chloride groups and positive control group ，while OD values were significantly reduced ；the expression levels of the above-mentioned protein and mRNA were reversed to varying degrees （P＜0.05 or P＜0.01）. Compared with lanthanum chloride high concentration group ，obvious cell calcification was observed in NF-κB signaling pathway agonist + lanthanum chloride group ，and OD value was significantly increased ；the above indexes were significantly reversed in cytoplasm and nucleus （P＜0.05 or P＜0.01）. CONCLUSIONS ：Lanthanum chloride can inhibit the calcification of VSMCs induced by high phosphorus ，and its mechanism may be related to the inhibition of NF-κB signaling pathway activation.

Determination of samarium oxide and lanthanum oxide in the air of workplace by inductively coupled plasmamass spectrometry / 中华劳动卫生职业病杂志

Objective@#To establish a method for the determination ofsamarium oxide and lanthanum oxide by inductively coupled plasmamass spectrometryin the air of workplace.@*Methods@#Samarium, lanthanum and their compounds in the air of workplace were collected through microporous filter. The samples were digested by nitricacid and perhydrol (V/V=4∶1) and detected by inductively coupled plasmamass spectrometry.@*Results@#The linear range ofsamarium oxide and lanthanum oxide was 0-50.00 μg/L, Sm2O3: y=0.0119x, r=0.9999; La2O3: y=0.0617x, r=0.9998. The detection limits were less than 0.1 μg/L, and the minimum detection concentration were less than 1.52×10-5 mg/m3. The sampling efficiency were 100%, the recovery rates were 95.70%-102.01%, and the precision were 0.78%-1.58%.@*Conclusion@#The indicators established in this study are conformed with the requirements of Chinese Occupational Standars of GBZ/T 210.4-2008, "The Guidelines for the Development of Occupational Hygiene StandarsMehods Part 4: Determination of Chemical Substances in the Air of Workplace".

Effects and mechanism of Lanthanum Citrate on proliferation and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 / 中华肝胆外科杂志

Objective To investigate the effect and the possible mechanism of Lanthanum Citrate on the proliferation and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 through the Hedgehog signaling pathway.Methods Hhsignaling pathway inhibitor KAAD-cyclopamine and Lanthanum Citrate in different concentrations were used to treat human hepatocellular carcinoma cell line SMMC-7721.Cell proliferation was detected by MTT method.The apoptosis rate was detected by Annexin V/PI flow cytometry.The expressions of the regulative genes,such as CyclinD1,p21,Caspase-3,Bcl-2,Gli1,Shh were detected by Western blot.The mRNA expressions of Gli1 and Shh were detected by q-PCR.Results In control group,SMMC-7721 cells were treated with 0.1 mmol/L Lanthanum Citrate group,and 15 μnol/L KAAD-cyclopamine for 48 h,and expression of CyclinD1 protein in each group was (1.41 ± 0.21),(0.71 ±0.08) and (0.53 ±0.11);p21 protein was (0.49 ±0.08),(0.97 ±0.09) and (1.55 ±0.13);Caspase-3 protein was (0.36 ± 0.05),(0.67 ± 0.10) and (0.89 ± 0.11);the relative expression of Bcl-2 protein in each group was (0.61 ± 0.10),(0.48 ± 0.05) and (0.24 ± 0.08).Gli1,Shh mRNA and Gli1,Shh protein expression were decreased.AnnexinV-FITC double staining showed Lanthanum Citrate group and KAAD-cyclopamine group had increased apoptosis rate of SMMC-7721 cells by flow cytometry.Conclusion Lanthanum Citrate inhibits the proliferation and promotes apoptosis in hepatocellular carcinoma SMMC-772 cells through suppressing hedgehog signaling pathway.

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day, Repeated Dose Study in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).</p><p><b>METHODS</b>In accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.</p><p><b>RESULTS</b>Significant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.</p><p><b>CONCLUSION</b>The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).</p>

Relationship between Gut Microbiota and Phosphorus Metabolism in Hemodialysis Patients: A Preliminary Exploration / 中华医学杂志(英文版)

Background@#Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism.@*Methods@#A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera.@*Results@#Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity.@*Conclusions@#Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.

Clinical Observation of Lanthanum Carbonate in the Treatment of Hyperphosphatemia in Uremic Patients Underwent Maintenance Hemodialysis / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in uremic patients underwent maintenance hemodialysis. METHODS:A total of 142 uremic patients with hyperphosphatemia under-went maintenance hemodialysis were selected from Xinqiao Hospital of Third Military Medical University and Chongqing Banan District Hospital of TCM during Jan. 2012-Dec. 2016. They were given Lanthanum carbonate chewable tablets with initial dose of 250 mg,tid,when serum phosphate level ranged 1.78-2.26 mmol/L or with initial dose of 500 mg,tid,when serum phosphate lev-el was >2.26 mmol/L. Drug dosage was adjusted according the level of serum phosphate during treatment. After 1,2,3 months of treatment,the levels of serum phosphate,serum calcium,albumin,parathyroid hormone(PTH)and alkaline phosphatase were de-tected and the corrected product of serum calcium and calcium phosphorus was calculated. The occurrence of ADR was observed. RESULTS:After 1,2,3 months of treatment,the levels of serum phosphate and the product of serum calcium and calcium phos-phorus were all decreased significantly compared to before trreatment,with statistical significance (P0.05). Total response rate was 93.7%. There were 19 cases of patients with mild adverse reactions. CONCLU-SIONS:Lanthanum carbonate in the treatment of hyperphosphatemia in uremic patients underwent maintenance hemodialysis shows good clinical response rate,can significantly reduce the levels of serum phosphate and the product of serum calcium and calcium phosphorus with good safety.

Study on Improvement Effect of Lanthanum Hydroxide on Chronic Renal Failure Hyperphosphatemia in Rats / 中国药房

OBJECTIVE:To study the improvement effect of lanthanum hydroxide on chronic renal failure (CRF) hyperphos-phatemia in rats. METHODS:CRF hyperphosphatemia rat model were induced and then randomly divided into model group,lan-thanum carbonate group [0.3 g/(kg·d)],calcium carbonate group [4.2 g/(kg·d)] and lanthanum hydroxide high-dose,medium-dose and low-dose groups [1.5,1,0.5 g/(kg·d)] with 10 rats in each group. They were given adenine 0.2 g/(kg·d)intragastrically in the morning,and then given relevant medicine intragastrically in the afternoon;a week later,they stopped taking adenine but con-tinued to take relevant medicine for 22 d. 10 normal rats were selected as normal control group. General examination was conduct-ed,and renal coefficient,serum contents of calcium,phosphorus,PTH,creatinine(Scr)and usea nitrogen(BUN)were detected after last medication as well as renal pathological change. RESULTS:Compared with normal control group,model group showed CRF sign,renal coefficient,the contents of phosphorus,PTH,Scr and BUN were increased,while the content of calcium was de-creased(P<0.01);renal section showed obvious pathological characteristics. Compared with model group,CRF sign of rats were improved in lanthanum carbonate group,calcium carbonate group and lanthanum hydroxide groups. The renal coefficient (except for lanthanum hydroxide high-dose group),serum contents of phosphorus(except for calcium carbonate group),PTH(except for lanthanum hydroxide low-dose group and calcium carbonate group),Scr(except for lanthanum hydroxide low-dose group and calci-um carbonate group)and BUN were all decreased,while serum content of calcium and calcium-phosphorucs product(only in calci-um carbonate group)was increased(P<0.05 or P<0.01). There was no statistical significance in other difference. The renal sec-tion pathological characteristics were improved. CONCLUSIONS:Lanthanum hydroxide can improve renal function and reduce the level of serum phosphorus in CRF hyperphosphatemia model rats.

Effects of Lanthanum Carbonate on Calcium and Phosphorus Metabolism in Maintenance Hemodialysis Patients with High Calcium and High Phosphorus / 中国药房

OBJECTIVE:To investigate the effects of lanthanum carbonate on calcium and phosphate metabolism in maintenance hemodialysis(MHD)patients with high calcium and high phosphorus. METHODS:A total of 40 MHD patients with high calcium and high phosphorus in our hospital during May 2014-May 2015 were divided into control group(22 cases)and observation group (18 cases)according to therapy plan. Both groups received diet guidance and MHD treatment. Control group was given Hydrotalcite chewable tablets 1 g,during meal,tid. Observation group was additionally given Lanthanum carbonate chewable tablets 500 mg(for patients with blood phosphorus ≥2.26 mmol/L)or 250 mg(for patients with blood phosphorus <2.26 mmol/L),during meal,tid (adjusting after 4 weeks).Both groups received treatment for 3 months.The calcium and phosphorus metabolism indexes[blood calci-um,blood phosphorus,calcium and phosphorus product,immunoreactive parathyroid hormone(iPTH)and alkaline phosphatase] and phosphorus reducing efficacies were observed in 2 groups before and after treatment,and the occurrence of ADR was recorded. RE-SULTS:Before treatment,there was no statistical significance in calcium and phosphorus metabolism indexes between 2 groups(P>0.05).After treatment,there was no statistical significance in calcium and phosphorus metabolism indexes of control group,iPTH or alkaline phosphatase of observation group compared to before treatment(P>0.05);blood calcium,blood phosphorus,calcium and phosphorus product of observation group were significantly lower than before treatment and also lower than control group at corre-sponding time,with statistical significance(P<0.05).Total response rate of phosphorus reducing in observation group(88.89%)was significantly higher than control group(40.91%),with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between observation group(11.11%)and control group(4.55%)(P>0.05). CONCLUSIONS:The lanthanum carbonate can effectively decrease blood calcium and blood phosphorus levels in MHD patients with good safety.

Effects of Lanthanum Carbonate on Calcium and Phosphorus Metabolism in Maintenance Hemodialysis Patients with High Calcium and High Phosphorus / 中国药房

OBJECTIVE:To investigate the effects of lanthanum carbonate on calcium and phosphate metabolism in maintenance hemodialysis(MHD)patients with high calcium and high phosphorus. METHODS:A total of 40 MHD patients with high calcium and high phosphorus in our hospital during May 2014-May 2015 were divided into control group(22 cases)and observation group (18 cases)according to therapy plan. Both groups received diet guidance and MHD treatment. Control group was given Hydrotalcite chewable tablets 1 g,during meal,tid. Observation group was additionally given Lanthanum carbonate chewable tablets 500 mg(for patients with blood phosphorus ≥2.26 mmol/L)or 250 mg(for patients with blood phosphorus <2.26 mmol/L),during meal,tid (adjusting after 4 weeks).Both groups received treatment for 3 months.The calcium and phosphorus metabolism indexes[blood calci-um,blood phosphorus,calcium and phosphorus product,immunoreactive parathyroid hormone(iPTH)and alkaline phosphatase] and phosphorus reducing efficacies were observed in 2 groups before and after treatment,and the occurrence of ADR was recorded. RE-SULTS:Before treatment,there was no statistical significance in calcium and phosphorus metabolism indexes between 2 groups(P>0.05).After treatment,there was no statistical significance in calcium and phosphorus metabolism indexes of control group,iPTH or alkaline phosphatase of observation group compared to before treatment(P>0.05);blood calcium,blood phosphorus,calcium and phosphorus product of observation group were significantly lower than before treatment and also lower than control group at corre-sponding time,with statistical significance(P<0.05).Total response rate of phosphorus reducing in observation group(88.89%)was significantly higher than control group(40.91%),with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between observation group(11.11%)and control group(4.55%)(P>0.05). CONCLUSIONS:The lanthanum carbonate can effectively decrease blood calcium and blood phosphorus levels in MHD patients with good safety.

Efficacy and safety of lanthanum carbonate in patients on maintenance hemodialysis:a Meta-analysis / 天津医药

Objective To assess the treatment efficacy and safety of lanthanum carbonate (LC) in patients on maintenance hemodialysis. Methods MEDLINE (1996—2014), Embase (1974—2014.12), Pubmed (1996—2014.12), Cochrane library, Chinese Wanfang database (1996—2014.12) and CNKI (1979—2014.12) were searched. Lanthanum carbonate and hemodialysis were used as Chinese and English search terms respectively, and the articles met the inclusion and exclusion criteria were used as supplements. Quality assessment and data mining were conducted by two independent investigators who performed Meta-analysis using RevMan5.2. Results Nine trials with 2 674 participants were included in this study. The Meta-analysis showed that there were similar blood levels of calcium [WMD=-0.24,95%CI:(-0.61)-0.14, P=0.21], phosphorus [WMD=0.14,95%CI:(-0.02)-0.30,P=0.08] and phosphate control rates (RR=0.91,95%CI:0.70-1.17, P=0.44) between control group and lanthanum carbonate group. There were lower incidence rates of hypercalcemia (RR=0.17, 95%CI:0.06-0.47, P=0.000 7) and blood levels of calcium-phosphorus product [WMD=-2.17,95%CI:(-3.99)-(-0.35), P=0.02], and higher levels of parathyroid hormone (iPTH, WMD=105.69, 95%CI:70.38-141.00, P<0.000 01) and bone-specific alkaline phosphatase (BAP, WMD=6.47, 95%CI:0.43-12.50, P=0.04) in these two groups. There were no significant differences in incidence rates of gastrointestinal adverse events between two groups. Conclusion Lanthanum carbonate should be used as preferred choice of phosphate binders to control serum phosphorus in patients on maintenance hemodialysis.

Ultrastructural observation of blood-brain barrier in the nude mouse model of brain metastases from lung cancer / 中国实验动物学报

Objective To observe the ultrastructure of blood-brain barrier in the nude mouse model of brain me-tastases from lung cancer by transmission electron microscopy using lanthanum nitrate tracing.Methods PC-9 cells (1 × 106/0.1 mL) in logarithmic phase were respectively injected into six nude mice ( model group) selected from eight nude mice randomly via the left ventricle, the other two mice without any treatment as the control group.The general status of the mice was observed after implantation.In the fourth week all the mice were sacrificed and brain tissue samples were taken and prepared for transmission electron microscopic observation using lanthanum nitrate tracing.besides, the lung and brain were removed and stained with HE to detect the presence of tumor metastasis.Results Mice in the model group began to lose weight almost simultaneously in the third week and became moribund slowly, and were all sacrificed at the fourth week when showing clear signs of cachexia.At autopsy, the thoraxes were clear, with normal lungs.Histology showed evidence of brain metastasis in all the six mice.The electron microscopy showed that lathanum nitrate tracer was escaped from the capillaries and diffusely or sparsely distributed in the brain tissues of the model group mice, however lathanum nitrate tracer was still confined in the capillary lumen in the mice of control group.Conclusions The diffuse lathanum nitrate tracer in the brain parenchymal tissue indicates the impairment of blood-brain barrier in the nude mouse model of lung cancer brain metastasis and the formation of these metastases is accompanied with the destruction of blood brain barrier.

Micro electrochemical mechanism of baicalin-metal complexes binding with hepatoma SMMC-7721 cell DNA / 中草药

Objective: The correlation of baicalin-metal (Y3+, La3+, and Ce3+) complexes (BMC) anti-tumor activity and the interactional ability of BMC binding with hepatoma SMMC-7721 cell DNA was investigated. Methods: Hepatoma SMMC-7721 cells DNA was extracted as a target, cyclic voltammetry and AC impedance were utilized to study the interaction between BMC and DNA, and the interaction mechanism between BMC and DNA was explored. Results: BMC and hepatoma SMMC-7721 cell DNA formed a non-electroactive supramolecular compounds through mixed-mode of electrostatic interaction, binding number m = 1, binding constant βBC = 1.27 × 105 L/mol, βBC-Y = 3.46 × 105 L/mol, βBC-La = 6.24 × 105 L/mol, and βBC-Ce = 7.29 × 106 L/mol. After BC binding with metal ions, its ability of binding to DNA significantly enhanced, and the strength order: BC-Ce > BC-La > BC-Y > BC. Conclusion: The ability of BMC binding with DNA consists with its cytotoxicity. After BMC binding with SMMC-7721 cell DNA, it could inhibit the cell proliferation and lead to the cell apoptosis, which illustrates the BMC exhibits an anti-tumor activity. The relevant results have given a reference for the study on the new anti-tumor complexes of Chinese materia medica.

Efficacy of Lanthanum carbonate in maintenance hemodialysis patients with hyperphosphatemia and high calcium times phosphate product / 中国综合临床

Objective To assess the efficacy and adverse reaction of Lanthanum carbonate in patients with hyperphosphatemia and high calcium times phosphate product receiving maintenance hemodialysis.Methods Twenty-three hemodialysis patients with serum phosphate ≥ 2.0 mmol/L and/or the serum calcium times phosphate product ≥ 4.52 mmol2/L2 were prescribed Lanthanum carbonate chewed with meals for 4 weeks.Blood (Hb), serum albumin (ALB), alanine amino shift enzyme (ALT), aspartic acid transaminase (AST) ,calcium(CA), phosphorus (P) calculated the product of calcium and phosphorus (Ca×P) and intact parathyroid hormone (iPTH) level were checked before and after Lantharum carbonate therapy.The adverse reactions were recorded concomitantly.Results Serum phosphate and the serum calcium time phosphate product significantly decreased after 1 month Lanthanum carbonate therapy((2.48±0.55) mmol/L vs.(1.83 ±0.37) mmol/L, (5.21 ± 1.35) mmol2/L2 vs.(4.10±0.96) mmol2/L2;t =2.742,2.936;P＜0.05).Serum calcium, iPTH level and blood cells count remained no change(P＞0.05), while serum ALT, AST concentration within normal range.Five patients complained affordable abdomen discomfort or upset.Conclusion Lantharum carbonate show to effectively and quickly control serum phosphorus levels and calcium time phosphate product in hemodialysis patients without inducing changes in serum calcium and should be considered an ideal phosphate binder.

Synthesis and characterization of lanthanum-incorporated hydroxyapatite coatings / 中国组织工程研究

BACKGROUND:Hydroxyapatite-coated titanium substrates improve the biocompatibility and have the property of intimating ossteointegration with host bonebed. However, hydroxyapatite lacks the necessary mechanical strength and degrades easily in the extracelular fluids, which may affect the stability of the titanium implant. OBJECTIVE:To study the synthesis and characterization of lanthanum-incorporated hydroxyapatite coatings. METHODS: Lanthanum-incorporated hydroxyapatite coatings were prepared by hydroxyapatite and 10%, 20% and 30% lanthanum, respectively, by means of sol-gel, which were then deposited on titanium substrates with dip-withdrawal technique. Surface morphology and crystaline microstructure of the coatings were observed by scanning electron microscope. The presence of functional groups for the obtained samples was performed by Fourier transform infrared absorption spectroscopy and X-ray diffraction. The Ca2+ concentration released from the coatings was measured by atomic absorption spectrometry for analysis of degradation property. RESULTS AND CONCLUSION: With the increase of lanthanum content, the diffraction peak and crystalinity of lanthanum-incorporated hydroxyapatite coatings were increased, but the whole structure of lanthanum-incorporated hydroxyapatites had little changes. The crystal structure maintained stable with charge balance. The lanthanum-incorporated hydroxyapatite coatings showed uniform and high-dense structure and were free of cracks, indicating the coatings had good bonding strength. Under the simulated biological environment, based on the determination of Ca2+ release from the coatings, we can conclude the lanthanum-incorporated hydroxyapatite coatings have a stronger acidoresistance.

Experimental study of lanthanum nitrate on rat pancreas in type 2 diabetes INSR,IRS1 and apoptosis of cells / 中国免疫学杂志

Objective:To explore the effects of lanthanum nitrate low-dose on 2 type diabetic rat pancreas INSR ,IRS1 and apoptosis of cells.Methods:The 50 male Wistar rats were randomly divided into normal control group (10) and model group(40),and were given normal diet and high-fat high-sugar diet.After 8 weeks,making the module intraperitoneal injection of streptozotocin (STZ,30 mg/kg) rats to induce type 2 diabetes model ,after a successful modeling experimental animals were divided into three groups namely the control group,diabetic model group and La(NO3)3 treatment group,three groups of rats were given daily saline,saline,lanthanum (0.2 mg/kg) nitrate administered a month ,then were sacrificed blood and pancreas.By radioimmunoassay to detect glucose ,insulin levels(in rat serum);by ELISA to detect the protein content of INSR and IRS 1(in rat serum);by immunohistochemistry to detect the protein expression levels of INSR and IRS1(in rat pancreas tissue);TUNEL apoptosis detection kit was used to detect pancreatic tissue percentage of apoptosis;HE staining was used to detect pathological changes of the pancreas.Results: Compared with the normal control group,diabetic model rats blood glucose and pancreatic tissue apoptosis rate were significantly increased ,blood insulin,INSR and IRS1 protein content and pancreatic tissue the protein expression levels of INSR and IRS 1 were significantly reduced ,difference was statistically significant ( P<0.01 );La( NO3 ) 3 treatment group blood glucose and pancreatic tissue apoptosis rate were slightly elevated ,blood insulin , INSR and IRS1 protein content and pancreatic tissue the protein expression levels of INSR and IRS 1 were slightly reduced significantly(P<0.05);Light microscopy showed pancreatic tissue in the control group closely arranged ,plump,large volume islet pancreatic tissue of diabetic rats in groups evacuate more smaller islet volume ,pancreatic tissue lanthanum nitrate basic set tight,plump,slightly islet volume small.Conclusion:Oral lanthanum nitrate can be lowered blood sugar levels and inhibiting apoptosis of pancreatic tissue ,increased insulin levels and the protein expression levels of INSR and IRS 1 in pancreatic tissue ,have a protective effect on diabetic rat pancreas .

A Meta-analysis of lanthanum carbonate for hyperphosphatemia in end-stage renal disease / 中华肾脏病杂志

Objective To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease (ESRD).Methods Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials,EMBASE,CNKI,Wanfang database.Data extracted from the literatures were analyzed with the Cochrane Collaboration's RevMan 5.1 software.Results Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR =1.00,95 ％ CI (0.92-1.09),P =0.97],and more effective than placebo [RR=4.69,95％ CI (2.63-8.39),P＜ 0.01] (intervention dose≤ 1500 mg) and [RR =18.92,95％ CI (7.42-48.22),P ＜ 0.01] (intervention dose ＞ 1500 mg).In comparison with calcium carbonate group,the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR =0.06,95 ％ CI (0.01-0.72),P =0.03],while the incidence of nausea [RR =1.80,95 ％ CI(0.70-4.64),P =0.22],vomiting [RR =3.94,95％ CI (0.45-34.38),P=0.22] and constipation [RR=0.82,95％ CI (0.49-1.37),P=0.45] were similar.The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo,with lower incidence of constipation [RR =0.19,95 ％ CI (0.06-0.59),P ＜ 0.01].Conclusions The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate.The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate,and the incidence of gastrointestinal adverse effect such as nausea,vomiting and constipation are similar with calcium carbonate.

Lanthanum carbonate vs conventional phosphate binders for the treatment of hyperphosphatemia in maintenance hemodialysis patients: a meta-analysis / 中华肾脏病杂志

Objective To assess the effect and safety of lanthanum carbonate vs conventional phosphate binders for hyperphosphatemia in patients undergoing maintenance hemodialysis.Methods According to the collaborative search strategy,MEDLINE (1996 to 2012.12),EBCO (1996 to 2012.12),the clinical control test database of Cochrane Library and Chinese Wanfang database (1996to 2012.12) were searched.Related literature,whether Published or not and meeting summary included,were searched by hand.Quality assessment and data extraction were conducted by two independent investigators.Meta-analysis was conducted by RevMan 5.0.The following outcomes were assessed:serum phosphorus levels,serum iPTH levels,serum calcium levels and adverse events.Results were expressed as OR with 95％ confidence interval for dichotomous outcomes and WMD with 95％ confidence interval for continuous outcomes.Results A total of 10 reports were identified which met the inclusion criteria.The meta-analysis showed that the efficacy of treating hyperparathyroidism in hemodialysis patients was similar between lanthanum carbonate and conventional phosphate binders (WMD =-0.06,95％ CI-0.27 to 0.15,P =0.57) and the incidences of discontinuing due to adverse events were also similar.However,there were fewer hypercalcemic episodes and lower serum calcium levels in the lanthanum carbonate group compared to calcium-based phosphorus binders group.Conclusion Lanthanum carbonate is effective and well tolerated in treating hyperphosphatemia in hemodialysis patients with fewer hypercalcemia and lower serum calcium levels compared to calciumbased phosphate binders.