聚苯乙烯磺酸镧治疗腺嘌呤性慢性肾衰竭动物模型钙磷代谢异常的实验研究

目的观察聚笨乙烯磺酸镧对大鼠腺嘌呤性慢性肾衰竭钙磷代谢的影响。方法雄性Wastar大鼠90只,参照Yokozawa方法腺嘌呤0．3g／（kg·d）灌胃,连续25d。将造模成功动物随机分为5组．分别为聚笨乙烯磺酸镧1．500、0．750、0．375g／kg 3个剂量组,阳性对照碳酸钙咀嚼片组及模型对照组．各组大鼠每日给相应供试品．连续用药22d。另设一组空白对照组。给药开始后7、14、21d称取动物体重,观察体重变化。给药10、21d后1h,自大鼠颈静脉取血检测血清PTH、Urea、Cre、P、Ca、K、RBC、Hb、PLT、HCT。给药22d后1h处死大鼠,摘取双侧肾脏,称重肾脏系数并进行病理组织学检查（待测）,进行统计学处理。结果聚苯乙烯磺酸镧在本试验中大剂量组[1．5g／（kg·d）]可明显降低腺嘌呤性慢性肾衰竭大鼠血清P水平,行显示出一定程度的降钾作用,对其他指标无影响。阳性对照组对血清钙有明显升高作用。结论聚苯乙烯磺酸镧可有效降低腺嘌呤性慢性肾衰竭大鼠血清磷水平,并显示出一定程度的降钾作用。     

应用微核实验和彗星电泳实验评价氯化镧90d喂养对小鼠遗传毒性作用

[目的]应用微核实验和彗星电泳实验评价氯化镧亚慢性染毒致小鼠遗传毒性作用. [方法]将100只SPF级ICR小鼠随机分为5组:4个氯化镧染毒组和1个对照组,每组20只,雌雄各半.5个剂量组分别以灌胃的方式给予不同浓度的氯化镧溶液(0、10、20、50和100 mg/kg).每周染毒6次,连续染毒13周后,取小鼠外周血进行彗星实验及镧含量的测定,取小鼠骨髓观察骨髓细胞微核率. [结果]镧染毒剂量达50 mg/kg时,彗星细胞的尾长及尾部DNA含量与对照组相比,差异有统计学意义(P＜0.05),小鼠骨髓细胞微核率与对照组相比,差异有统计学意义(P＜0.05).4个氯化镧染毒组血液中均有不同程度的镧的蓄积,与对照组相比,差异均有统计学意义(P＜0.05). [结论]稀土镧元素可以在血液中蓄积,具有一定的遗传毒性.     

Ordered mesoporous silica modified with lanthanum for ibuprofen loading and release behaviour

The ordered mesoporous silicas SBA-15 and KIT-6, modified with lanthanum, have been for the first time applied in investigation of ibuprofen adsorption and release. The materials of hexagonal and regular structure were obtained by the hydrothermal method using a triblock copolymer Pluronic P123 as a template. The mesoporous silicas were impregnated with an aqueous solution of lanthanum(III) chloride in the amount necessary to obtain 1, 3 and 5 wt.% La loading. The physicochemical properties of the modified silicas were characterised by X-ray diffraction, transmission electron microscopy, UV–Vis spectrophotometry and low-temperature nitrogen sorption. The results showed that lanthanum strongly determined structural as well as textural properties of the silicas. The samples of modified silica were checked for the ability to adsorb and release of ibuprofen. The storage capacity of the modified silicas obtained increased with increasing their average pore diameter and percentage content of lanthanum. The amount of ibuprofen adsorbed onto KIT-6 silica modified with La was higher than that adsorbed onto SBA-15 materials. The high coverage of lanthanum on the surface of KIT-6 and SBA-15 solids was found to increase the amount of ibuprofen and the rate of its release.     

碳酸镧咀嚼片引起便秘及腹部影像学异常的病例分析

目的 为临床合理使用碳酸镧咀嚼片出现影像学异常提供分析参考。方法 通过对1例CKD5期高磷血症患者使用碳酸镧咀嚼片引起便秘和影像学异常的病例进行分析,药师协助临床查找原因,并对患者进行用药指导和监护随访。结果 经过分析,影像学异常为患者错误服用碳酸镧引起的影像学表现,经过通便处理,影像学恢复正常,临床药师由此制定了碳酸镧咀嚼片的使用监护流程,保证了患者的安全正确用药。结论 临床药师对使用碳酸镧咀嚼片的患者进行详细的用药指导和持续随访,可促进患者正确用药。     

Simplification of the modified Gallyas method

The Gallyas method is a silver impregnation technique that is essential in the field of neuropathology because of its high sensitivity for the detection of argentophilic inclusion bodies in the central nervous system. In Japan, the Gallyas method has improved and is widely used as the “modified Gallyas method”. However, this method is not popularly used in general pathology laboratories because of the need for special reagents, several staining processes, and skilled techniques. The objective of the current study was to provide a simplified Gallyas method. We omitted the lanthanum nitrate step from the staining process and verified the adequacy in comparison with the original method as well as immunohistochemistry, using specimens from patients of Alzheimer's disease, argyrophilic grain disease, multiple system atrophy, Pick's disease, and Lewy body disease. The simplified method provided good staining to all the structures in archival tissues, compared with the modified Gallyas method in a significantly shorter staining time. The lanthanum nitrate step can be omitted from the modified Gallyas method, resulting in reduction in the number of reagents required and shortening of the staining time.     

Lanthanum-induced alterations in the distribution of actin filaments in human keratinocytes

The effects of La³⁺ on the distribution and organization of actin in human keratinocytes were examined with rhodamine-phalloidin staining. At 0.2 and 0.02 mM concentrations, La³⁺ induced redistribution and organization of actin. Thick bundles of actin filaments appeared, as did fine ripple-like short bundles and polygonal structures. Thick, ribbon-like assemblages of actin were crescent-shaped or semi-circular. These changes were quite similar to those induced by TPA. The effects of La³⁺ were discussed with reference to Ca²⁺.     

Development of the blood-testis barrier in the domestic fowl (Gallus domesticus)

The formation of the blood-testis barrier (BTB) in the domestic fowl was studied at the electronmicroscopic level employing lanthanum as a tracer. No effective barrier could be demonstrated in testes before puberty, although several components of the Sertoli junctional complex such as focal tight junctions and desmosomes were already existent. The time of onset of meiosis after hatching showed great individual variation and meiosis did not occur synchronously in the tubules of a given testis. An effective barrier could first be detected in tubules containing early spermatids, and in which spermatogonia and primary spermatocytes at the leptotene stage were still within the open compartment. Thus, barrier formation was correlated with the occurrence of haploid germ cells. Complete compartmentation of seminiferous tubules, leaving only spermatogonia within the open compartment, was attained in tubules containing elongated spermatids of the maturation phase. In these tubules, primary spermatocytes at the leptotene stage were situated in an intermediate compartment.     

Real-World Dose-Relativity,Tablet Burden,and Cost Comparison of Conversion Between Sevelamer Hydrochloride/Carbonate and Lanthanum Carbonate Monotherapies

Purpose

Sevelamer hydrochloride/carbonate (SH/C) and lanthanum carbonate (LC) are noncalcium-based phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objectives of this study were to examine the dose-relativity, tablet burden, and cost difference of bidirectional conversion between SH/C and LC monotherapy in a large cohort of real-world patients with ESRD.

Methods

This retrospective cohort study included three 30-day preconversion periods (days −90 to −61, −60 to −31, and −30 to −1) followed by three 30-day postconversion periods (days 1 to 30, 31 to 60, and 61 to 90); day 0 was the index date of conversion. The full analysis population (FAP) comprised two cohorts: SH/C to LC (S–L) converters and LC to SH/C (L–S) converters. The SH/C:LC dose-relativity ratio was assessed in the dose-relativity subset, defined as patients whose serum phosphate levels fell within a caliper range of ±0.5 mg/dL in the final preconversion (days −30 to −1) and postconversion (days 61 to 90) periods. Tablet burden and phosphate binder costs were assessed in the FAP. Phosphate binder costs were based on average wholesale prices.

Findings

The FAP contained a total of 303 patients, comprising the S–L (128 patients) and L–S (175 patients) converter cohorts. The dose-relativity subset contained 159 patients, 72 from the S–L cohort and 87 from the L–S cohort. The overall mean SH/C:LC dose-relativity ratio was 2.27 (95% CI, 2.04 to 2.52). In SH/C dose strata >800 to 2400, >2400 to 4800, >4800 to 7200, and >7200 mg/d, overall mean dose-relativity ratios were 0.79 (95% CI, 0.57 to 1.10), 1.45 (95% CI, 1.20 to 1.75), 2.05 (95% CI, 1.75 to 2.39), and 3.24 (95% CI, 2.89 to 3.66), respectively. The overall mean tablet burden was 6.6 tablets per day lower with LC monotherapy than with SH/C monotherapy (95% CI, −7.1 to −6.0; P < 0.0001). The overall mean binder cost/patient per month was $1080.40 for SH/C compared with $1006.20 for LC, corresponding to a mean binder cost saving for LC of $74.20/patient per month (95% CI, −141.80 to −6.63; P = 0.032). SH/C >7800 mg/d was the inflection point at which conversion to LC resulted in mean cost savings. Patients requiring SH/C >7800 mg/d comprised 50% of the FAP.

Implications

Converting patients with ESRD and hyperphosphatemia from SH/C to LC monotherapy offers potential drug cost savings and a significant reduction in the daily tablet burden, without compromising the effective management of serum phosphate levels.     

Cost-Minimization Analysis of Lanthanum Carbonate Versus Sevelamer Hydrochloride in US Patients With End-stage Renal Disease

Purpose

Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium-free phosphate binders used in the clinical management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objective of this analysis was to assess the cost-effectiveness of LC monotherapy compared with SH monotherapy in US patients with ESRD in a clinical practice setting.

Methods

This was a post hoc assessment of phosphate binder costs among US patients with ESRD who converted from SH to LC monotherapy in a previously published, 16-week, Phase IV, real-world study. Calculations of drug costs used both average wholesale price (AWP) and wholesale acquisition cost (WAC).

Findings

There were 953 patients with available baseline SH dose data; 950 also had a recorded LC dose >0 mg at baseline, and 691 had dose data available for both SH at baseline and LC at week 16 (post hoc analysis population). Baseline demographic characteristics were similar in excluded patients and the post hoc analysis population. Mean (SD) serum phosphate levels were 5.91 (1.66) mg/dL at baseline and 5.93 (1.85) mg/dL after conversion to LC monotherapy for 16 weeks. Mean AWP costs were US$35.72 (16.89) per day at baseline and US$24.69 (8.28) per day at week 16, yielding an overall mean cost change (defined as LC cost − SH cost) of −US$11.03 (16.37) per day in favor of LC. The overall mean WAC cost change was −US$9.17 (13.64) per day. Within baseline SH dose subgroups 2400 to 4800, >4800 to 7200, >7200 to 9600, and >9600 mg/d, the mean AWP cost change ranged from US$2.78 (9.26) per day in favor of SH for the 2400- to 4800-mg/d subgroup to −US$33.15 (12.58) per day in favor of LC for the >9600-mg/d subgroup. Mean WAC cost changes showed a similar trend, ranging from US$2.33 (7.72) per day to −US$27.59 (10.48) per day. Linear regression analyses revealed that the inflection SH doses corresponding to a mean cost change of zero were 4905 mg/d (AWP) and 4908 mg/d (WAC). For the 455 (66%) patients in the post hoc analysis population who had baseline SH doses at least as high (≥5600 mg/d) as these point estimates, the mean SH:LC tablet ratio was ≥3.7, indicating a mean reduction in the tablet burden after conversion to LC of ≥73%.

Implications

This real-world assessment of comparative phosphate binder drug costs between SH and LC among US patients with ESRD indicates that average cost savings with LC use increased with increasing SH doses. Conversion to LC from SH ≥5600 mg/d reduced drug costs and tablet burden while maintaining serum phosphate levels.