A conveniently synthesized Pt (IV) conjugated alginate nanoparticle with ligand self-shielded property for targeting treatment of hepatic carcinoma

The clinical translation remains a major challenge for platinum drug loaded nanoparticle due to the complexity of composition and preparation. Here we employed only three ingredients to prepare Pt (IV) prodrug-loaded ligand-induced self-assembled nanoparticles (GA-ALG@Pt NPs) via facile one-pot route for liver tumor treatment. GA-ALG@Pt NPs were found equipped with intelligently ligand self-shielded property in which the internal GA could be induced to expose by initial cellular recognition, resulting in strengthened cellular uptake (20%-30%) and prolonged blood circulation time (3.43 times). Appreciable tumor targeting ability (2 times) and especially tumor selectivity (2.5 times) were obtained. Glutathione-triggered release of therapeutic agent generated satisfactory antitumor effect. Bio-safety is also a distinguishing feature of GA-ALG@Pt NPs that greatly relief the nephrotoxicity and systematic toxicity of cisplatin. This conveniently synthesized nanoparticle processes superior targeting capacity and biosecurity, supplying an effective approach to translational cancer therapy in the future.     

Calcium carbonate as a phosphate binder in dialysis patients: Evaluation of an enteric-coated preparation and effect of additional aluminium hydroxide on hyperaluminaemia

Summary Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure; however, a high frequency of hypercalcaemia has been reported. To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect, we conducted a double-blind, crossover trial in 21 patients undergoing chronic haemodialysis. Aluminium hydroxide therapy was replaced with calcium carbonate. The subjects then randomly received either an enteric-coated or a gastric-coated preparation. Calcium carbonate (3.1–3.6 g/d) controlled serum phosphate concentrations as effectively as aluminium hydroxide (2.9 g/d). Concurrently, there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin, the latter suggesting a decrease in bone turnover. Overall, hypercalcaemic episodes developed in 9 patients (43%) and occurred at a considerable frequency (33 episodes per 100 patient-months) during treatment with the gastric-coated formulation. Following conversion to enteric-coated calcium carbonate (3.6 g/d) patients had fewer occurrences of hypercalcaemia (12 episodes per 100 patient-months,P<0.05) and, as compared to the gastric-coated preparation, increases in serum calcium >3.00 mmol/l were not observed at all. Hyperaluminaemia was regressive during therapy with calcium carbonate, but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine, indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium.We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients. However, undesirable hypercalcaemic episodes may occur, the frequency and severity of which can be lowered by the use of an enteric-coated preparation. Concomitant use of aluminium hydroxide and calcium carbonate should be restricted to patients in whom the degree of aluminium accumulation is monitored by serial desferrioxamine tests.     

Salivary factors related to caries in pregnancy: A systematic review and meta-analysis

BackgroundThe authors of this meta-analysis aimed to assess saliva-related caries risk factors, including calcium and phosphate, hydrogen ion concentration, buffer capacity, Streptococcus mutans and Lactobacillus counts, flow rate, and decayed, missing and filled teeth index in each trimester during pregnancy.Types of Studies ReviewedThe authors searched electronic databases up to July 1, 2019. Eligible observational studies were included. The authors assessed the quality of the included studies by using the Joanna Briggs Institute scale. To estimate the effects of pregnancy, standardized mean differences with 95% confidence intervals were pooled using the random-effects model. Subgroup analysis and meta-regression were used to explore heterogeneity. Publication bias was assessed using Begg and Egger tests.ResultsTwenty-nine studies were included in the meta-analysis, representing 1,230 pregnant women in the case groups and 715 in the control groups (nonpregnant women). The results showed that salivary calcium concentration decreased in the third trimester, salivary phosphate decreased in the second and third trimesters, saliva hydrogen ion concentration decreased in the first and third trimesters, stimulated saliva flow rate increased in the third trimester, and salivary S mutans count increased in the second and third trimesters. In addition, the results showed that saliva calcium, phosphate, S mutans, and buffer capacity amounts had changed from the first trimester to the third.Conclusions and Practical ImplicationsIn the third trimester, most salivary factors related to caries change and can increase the risk of developing caries in the future. Interventions and screening for caries prevention in pregnancy should start in the first or second trimesters.     

Effect of buffer conditions on CYP2C8-mediated paclitaxel 6α-hydroxylation and CYP3A4-mediated triazolam α- and 4-hydroxylation by human liver microsomes

Abstract

1.?Buffer conditions in in vitro metabolism studies using human liver microsomes (HLM) have been reported to affect the metabolic activities of several cytochrome P450 (CYP) isozymes in different ways, although there are no reports about the dependence of CYP2C8 activity on buffer conditions.

2.?The present study investigated the effect of buffer components (phosphate or Tris-HCl) and their concentration (10–200?mM) on the CYP2C8 and CYP3A4 activities of HLM, using paclitaxel and triazolam, respectively, as marker substrates.

3.?The K_m (or S₅₀) and V_max values for both paclitaxel 6α-hydroxylation and triazolam α- and 4-hydroxylation, estimated by fitting analyses based on the Michaelis–Menten or Hill equation, greatly depended on the buffer components and their concentration.

4.?The CL_int values in phosphate buffer were 1.2–3.0-fold (paclitaxel) or 3.1–6.4-fold (triazolam) higher than in Tris-HCl buffer at 50–100?mM. These values also depended on the buffer concentration, with a maximum 2.3-fold difference observed between 50 and 100?mM which are both commonly used in drug metabolism studies.

5.?These findings suggest the necessity for optimization of the buffer conditions in the quantitative evaluation of metabolic clearances, such as in vitro–in vivo extrapolation and also estimating the contribution of a particular enzyme in drug metabolism.     

GC-MS法测定金银花中12种有机磷农药的残留量

目的：建立金银花中12种有机磷农药残留量的测定方法。方法：样品以丙酮超声提取,并采用凝胶渗透色谱（GPC）和氨基固相萃取柱（NH2-SPE）结合的方法进行净化,选用气相色谱与质谱串联技术（GC-MS）在DB．5MS毛细管柱上用程序升温技术分离,采用选择离子检测方式,以保留时间和特征离子进行目标成分的定性鉴别,外标法对样品进行测定。结果：12种有机磷农药在50-1000μg·L^-1范围内呈良好的线性关系,12种农药的方法定量限在3．6～7．2μg·k^-1之间,三个水平添加回收率在72．2l％～107．72％,RSD〈10％（n=9）。结论：本方法灵敏度高,重复性好,可用于全银花中12种有机磷农药残留的检测。     

In vitro and in vivo evaluation of the influence of type III NaPi co-transporter activity during apoptosis on <Superscript>99m</Superscript>Tc-(V)DMSA uptake in the human leukaemic cell line U937

Purpose Pentavalent ^99mTc-dimercaptosuccinic acid [^99mTc-(V)DMSA or (V)DMSA] is a marker of phosphate transport, entering cells specifically through type III NaPi co-transporters. Phosphate ion is known to be involved in cell metabolism, including the apoptotic cell death process. As phosphate accumulation decreases during apoptosis, we investigated the influence of type III NaPi co-transporter activity on (V)DMSA uptake during this type of cell death.Methods Uptake of (V)DMSA and phosphate was compared in a leukaemic cell line (U937) in vitro model after induction of apoptosis by a chemotherapeutic agent, etoposide (VP16). (V)DMSA biodistribution in nude mice during apoptosis was also investigated in a U937 xenograft in vivo model. The percentage of apoptosis in vitro and ex vivo was determined with annexin V fluorescein by flow cytometry.Results The in vitro results showed that, in parallel with the decrease in phosphate uptake during apoptosis, (V)DMSA accumulation is negatively correlated with the percentage of apoptosis. Biodistribution studies showed decreased accumulation of (V)DMSA in tumours after treatment with VP16. Animal studies also confirmed an inverse correlation between percentage of apoptosis in tumours and (V)DMSA uptake.Conclusion The activity of type III NaPi co-transporter is inhibited during the early stages of apoptosis, leading to differential incorporation of (V)DMSA in viable cells and apoptotic cells both in vitro and in vivo.     

右倍他米松磷酸钠注射液的制备、质量控制及稳定性考察

目的根据临床需要,研发右倍他米松磷酸钠注射液,考察其稳定性并建立质量控制方法。方法拟订处方组成与制备工艺,并进行性状、鉴别、pH值、有关物质检查等研究,采用高效液相色谱法测定右倍他米松磷酸钠含量,通过影响因素试验、恒温加速试验和长期留样试验考察其稳定性。结果按优化的最佳处方及工艺制备的3批中试样品均合格。结论该制剂处方工艺合理可行,质量可控,稳定性良好;含量测定方法重现性好,专属性强,测定结果在规定的限度内。     

宜昌市夷陵区磷矿职工生活质量研究

目的评价湖北省宜昌市夷陵区磷矿职工的生活质量并探讨其影响因素。方法采取随机整群抽样方法,使用社区人群功能状态测定量表（COOP/WONCA）中文版对1800名磷矿职工进行调查,运用 Logistic 回归分析探讨影响生活质量的因素。结果22.9%（390/1702）的职工生活质量较好,56.1%（955/1702）为一般,生活质量各维度评分等级在中等及以上者均超过50%。多因素分析结果显示,影响磷矿职工生活质量的危险因素为女性、年龄较大、回家频繁、家人健康状况不佳和慢性病;保护因素为较高的文化程度、非独居方式和一定频率的食用高脂类食物。结论该区磷矿职工的生活质量为中等偏上,在今后的实际工作中,应针对生活质量的可能影响因素,采取科学有效的干预措施。     

Bioavailable dietary phosphate,a mediator of cardiovascular disease,may be decreased with plant-based diets,phosphate binders,niacin, and avoidance of phosphate additives

Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.     

Surface treatments of silver rods with enhanced iodide adsorption for I-125 brachytherapy seeds

This study described an effective method to load ¹²⁵I on silver rods for the preparation of a brachytherapy source. We tested various ligands on the silver rod surface to screen the one with the highest adsorption and specific radioactivity. In addition, we investigated the effect of surface etching to increase the adsorption capability followed by the extended surface area. We also found that the use of an oxidant during iodide adsorption can increase the loading significantly. The maximum activity of 137.90 MBq/rod (3.7269 mCi/rod) was achieved on the etched silver rods with phosphate ligand and hydrogen peroxide as an oxidant. In addition, this is 4.5-fold higher than that of the conventional chloride treatment method.