Dimephosphone analogs: I. Synthesis and structure of some dimephosphone aryl- and acylhydrazones

Dimephosphone (2-dimethoxyphosphoryl-2-methylpentan-4-one) phenyl-, nitrophenyl-, benzoyl-, and 4-nitrobenzoylhydrazones were synthesized. The compounds in crystals were shown to have a steric form exclusively of the E-isomer. The structure of hydrazones in solution is defined by the nature of the substituents and the solvent and the time of storage of the solution. The dimephosphone aroylhydrazones in acid solutions exist in several possible forms: the isomers at the imine bond, the conformers at the amide bond, and a cyclic tautomer (1,3,4-oxadiazoline).     

Interpretation of 41Ca data using compartmental modeling in post-menopausal women

Calcium-41 (t(1/2) = 10(5) years) can be used after a single dose to follow calcium metabolism over a subject's lifetime. The aims of this study were to expand a (41)Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance for the design and interpretation of (41)Ca studies. Forty-two women >5 years post-menopause were given (41)Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ~5 years while subjects were free living. Urinary (41)Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (n = 13), studied previously in a 3-week balance and full kinetic study with (45)Ca, agreed with those using (41)Ca methodology. Thus, rates of bone resorption can be estimated from (41)Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation.     

Synthesis and Therapeutic Use of Dimephosphone

Abstract

The synthesis of dimephosphone (1) was carried out on Pudovik's reaction.     

Separation and determination of <Superscript>241</Superscript>Am in urine samples from radiation workers using PC88-A and alpha spectrometry

Bioassay technique is used for the estimation of actinides present in the body based on their excretion rate through body fluids. For occupational radiation workers urine assay is the preferred method for monitoring of chronic internal exposure. Determination of low concentrations of actinides such as plutonium, americium and uranium at low level of mBq in urine by alpha spectrometry requires pre-concentration of large volumes of urine. This article deals with standardization of analytical method for the determination of ²⁴¹Am isotope in urine samples using Extraction Chromatography (EC) and ²⁴³Am tracer for radiochemical recovery. The method involves oxidation of urine followed by co-precipitation of americium along with calcium phosphate. This precipitate after treatment is further subjected to calcium oxalate co-precipitation. Separation of Am was carried out by EC column prepared by PC88-A (2-ethyl hexyl phosphonic acid 2-ethyl hexyl monoester) adsorbed on microporous resin XAD-7 (PC88A-XAD7). Am-fraction was electro-deposited and activity estimated using tracer recovery by alpha spectrometer. Ten routine urine samples of radiation workers were analyzed and consistent radiochemical recovery was obtained in the range 44–60% with a mean and standard deviation of 51 and 4.7% respectively.     

Thermal, UV, FTIR, and XRD studies of urinary stones

Various crystals are seen in human urine. Oxalate, Phosphate, Uric acid, and Urate crystals are generally seen in urinary calculi. Calcium stones are most common, comprising 75 % of all urinary calculi. They may be pure calcium oxalate or calcium phosphate or a mixture of both. Many stones are not homogeneous. Low calcium intake increases the intestinal absorption of calcium, thus decreasing the amount of calcium available in the intestinal tract to form insoluble complexes with Oxalate. Consequently, a higher amount of oxalate is available for intestinal absorption and as a result, urinary oxalate excretion increases. Mineral water consumption did not reduce urinary oxalate excretion. High urinary excretion and concentration of magnesium decrease both the nucleation and growth rates of calcium oxalate crystals in urine, because of the higher solubility of magnesium oxalate compared with calcium oxalate. Analytical results show calcium oxalate to be one of the major inorganic components of renal stones and found to be present in almost all kidney and bladder stones. About 39.5 % of the total composition of the calculi is found to contain purely calcium oxalate and also hydroxyl apatite. The ten samples are a mixture of calcium oxalate and phosphate stones. Four samples are calcium oxalate as major composition and the remaining are calcium phosphate as major composition. These kidney stones are taken photographically and size of the stone are measured using optical microscopy. These qualitative analyses are also confirmed by UV, FTIR, DSC, and XRD analysis.     

Determination of plutonium isotopes in urine samples from radiation workers using <Superscript>236</Superscript>Pu tracer,anion exchange resin and alpha spectrometry

Bioassay technique is used for the estimation of actinides present in the body based on their excretion rate through body fluids. For occupational radiation workers urine assay is the preferred method for monitoring of chronic internal exposure. Determination of low concentrations of actinides such as plutonium, americium and uranium at low level of mBq in urine by alpha spectrometry requires pre-concentration of large volumes of urine. This paper deals with standardization of analytical method for the determination of Pu-isotopes in urine samples using anion exchange resin and ²³⁶Pu tracer for radiochemical recovery. The method involves oxidation of urine followed by co-precipitation of plutonium along with calcium phosphate. Separation of Pu was carried out by Amberlite, IRA-400, anion exchange resin. Pu-fraction was electrodeposited and activity estimated using tracer recovery by alpha spectrometer. Twenty routine urine samples of radiation workers were analyzed and consistent radiochemical tracer recovery was obtained in the range 74–96% with a mean and standard deviation of 85 and 6% respectively.     

Mathematical modeling of the role of bone turnover in pH regulation in bone interstitial fluid

Background and aimsBone turnover is strongly affected by pH of surrounding fluid, and in turn plays a role in maintaining systemic pH, however the quantitative contribution of bone processes to pH regulation is not known. Our goal was to develop a mathematical model describing pH regulation in the interstitial fluid and to examine the contribution of hydroxyapatite dissolution and precipitation to pH regulation.Materials and methodsWe modeled twelve reversible equilibrium reactions of sixteen calcium, phosphate, hydrogen and carbonate species in the interstitial fluid and examined the buffering capacity and range. The effect of hydroxyapatite dissolution and precipitation was modeled by assuming that the calcium, phosphate and hydroxide contained in the bone volume adjacent to the interstitial fluid is instantaneously added to or removed from the interstitial fluid.ResultsThe carbonate buffer was found to dominate electrochemical buffering system of the bone interstitial fluid. Nevertheless, the phosphate added during dissolution of bone hydroxyapatite significantly improved the interstitial fluid buffering capacity. In contrast, hydroxyapatite precipitation had limited effect on the interstitial fluid pH regulation.ConclusionThis study provides mechanistic insights into the physicochemical processes underlying the known role of bone turnover processes in regulation of body pH homeostasis.     

Determination of uranium isotopes in urine samples from radiation workers using 232U tracer, anion-exchange resin and alpha-spectrometry

Bioassay technique is used for the estimation of actinides present in the body based on the excretion rate of body fluids. For occupational radiation workers urine assay is the preferred method for monitoring of chronic internal exposure. Determination of low concentrations of actinides such as plutonium, americium and uranium at low level of mBq in urine by alpha-spectrometry requires pre-concentration of large volumes of urine. This paper deals with standardization of analytical method for the determination of U-isotopes in urine samples using anion-exchange resin and ²³²U tracer for radiochemical recovery. The method involves oxidation of urine followed by co-precipitation of uranium along with calcium phosphate. Separation of U was carried out by Amberlite, IRA-400, anion-exchange resin. U-fraction was electrodeposited and activity estimated using tracer recovery by alpha-spectrometer. Eight routine urine samples of radiation workers were analyzed and consistent radiochemical tracer recovery was obtained in the range of 51% to 67% with a mean and standard deviation of 60% and 5.4%, respectively.     

Adsorption of fluoride ions onto carbonaceous materials

The characteristics of fluoride ion adsorption onto carbonaceous materials were derived as adsorption isotherms at different temperatures and in different pH solutions. The fluoride ion was adsorbed into pores in carbonaceous materials produced from wood; the larger the specific surface area, the more fluoride ions adsorbed. Bone char was the most effective adsorbent. The composition of bone char includes calcium phosphate, calcium carbonate, and so on. This suggests that the phosphate ion in bone char was exchanged with a fluoride ion. Moreover, the mechanism of fluoride ion adsorption onto bone char is clearly chemical in nature because the amount of fluoride ion adsorbed onto bone char increased with increasing temperature and decreasing pH. The amount of fluoride ion adsorbed onto bone char was also shown to depend on the concentration of sodium chloride in solution because of the "salting-out" effect. The adsorption of fluoride ion onto bone char is endothermic. Bone char can be utilized to remove fluoride ions from drinking water.     

Evaporite Borate‐Containing Mineral Ensembles Make Phosphate Available and Regiospecifically Phosphorylate Ribonucleosides: Borate as a Multifaceted Problem Solver in Prebiotic Chemistry

RNA is currently thought to have been the first biopolymer to support Darwinian natural selection on Earth. However, the phosphate esters in RNA and its precursors, and the many sites at which phosphorylation might occur in ribonucleosides under conditions that make it possible, challenge prebiotic chemists. Moreover, free inorganic phosphate may have been scarce on early Earth owing to its sequestration by calcium in the unreactive mineral hydroxyapatite. Herein, it is shown that these problems can be mitigated by a particular geological environment that contains borate, magnesium, sulfate, calcium, and phosphate in evaporite deposits. Actual geological environments, reproduced here, show that Mg²⁺ and borate sequester phosphate from calcium to form the mineral lüneburgite. Ribonucleosides stabilized by borate mobilize borate and phosphate from lüneburgite, and are then regiospecifically phosphorylated by the mineral. Thus, in addition to guiding carbohydrate pre‐metabolism, borate minerals in evaporite geoorganic contexts offer a solution to the phosphate problem in the “RNA first” model for the origins of life.     

The Kinetics and Mechanism of the Hydrolysis of Creatinine in Urine

Abstract

Creatinine in urine concentrations are routinely measured at Aldermaston by an autoanalyser, using the Jaffe reaction, as an index of urinary excretion rates. These values are used in calculations to estimate the body content of radionuclides from their urinary excretion rates.

Unfortunately, creatinine in urine concentrations gradually decrease with sample age due to pseudo first order hydrolysis of creatinine to give creatine in the presence of ammonia. This reaction may be arrested or reversed by mineral acid.

After storage at ambient temperatures for several weeks the creatinine in urine concentration falls by around 20%, so it is good practice to analyse samples soon after provision.

The activation energy for the hydrolysis of creatinine in urine is around 60 KJ/mol over the range 20–70 °C. Hence, raising the temperature by 10 [ddot]C approximately doubles the reaction rate.     

亚硒酸钠对大鼠代谢产物影响的核磁共振研究

本文采用核磁共振(^1H NMR)技术研究了在最高耐受摄入量条件下补充亚硒酸钠对大鼠尿液代谢产物的影响。结果表明,在大鼠尿液中甲酸、乙酸、乳酸、丙氨酸、琥珀酸、甘氨酸、马尿酸、苯丙氨酸、色氨酸等代谢物谱峰信号显著增强,而柠檬酸、肌酸、尿素、尿甘素和氧化三甲胺(TAMO)的谱峰信号则显著降低。乳酸、柠檬酸和琥珀酸是体内三羧酸循环的中间产物,其代谢异常是能量代谢紊乱的标志;马尿酸、苯丙氨酸、丙氨酸的代谢异常与肾小球的滤过和回收功能有关;乙酸和甘氨酸的代谢异常则是肝功能损伤的标志,组织切片的结果也证明大鼠的肝和肾已经发生损伤,与^1H NMR的结果相一致。采用HPLC检测到补充亚硒酸钠后尿液中8-OHdG(8-hydroxy1-2′-deoxyguansoine)水平显著升高,证明体内氧化损伤的发生。以上结果表明,在最高耐受摄入量条件下补充亚硒酸钠是不安全的,用NMR方法对阐明硒的毒理学分子基础是有效的。     

Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

Pharmacological evaluation of LiuWei Zhuanggu Granules in rats

Many commonly consumed foods, herbs and spices contain a complex array of naturally occurring bioactive molecules called phytochemicals, which may confer health benefits. In this study, the impact of LiuWei Zhuanggu Granules (LWZGG) on mineral metabolism in osteopenia development was evaluated. Results showed that serum estrogen, bone gla protein (BGP), and calcitonin (CT) levels, bone Ca, Zn and Cu levels, femur, lumbar vertebrae and trabecular bone density, tibia maximum stress and maximum bending strength were increased, and serum parathyroid hormone (PTH), serum and urine Ca, Zn and Cu levels were decreased in rat bone. It can be concluded that LWZGG is useful to improve bone quality in ovariectomized (OVX) rats.     

Formation of calcium phosphates in gelatin with a novel diffusion system

The present paper demonstrated a novel and simple diffusion system to precipitate calcium phosphates in gelatin gel. In this system, a gelatin cup was specially used as the membrane separating reservoirs of calcium and phosphate ions. Relative to the conventional diffusion system, the novel one in our experiment decreased the time required for the deposition from 5-7 days to 20 h and increased the amount of the precipitated mineral phases significantly. The influence of pH values and concentrations of calcium and phosphate solutions buffered with Tris-HCl and NaOH, respectively, was investigated. The results showed that precipitation of the mineral phase at low pH values (7 for calcium and 11 for phosphate) and concentrations (200 mM for calcium and 15 mM for phosphate) resulted in the formation of plate-like octacalcium phosphate (OCP) crystals. With increasing the pH values of calcium and phosphate solutions to 8 and 12, respectively, spherical amorphous calcium phosphate (ACP) particles were obtained uniquely. Furthermore, flower-like hydroxyapatite (HAP) aggregates composed of many nano-sized needles were formed from the solutions with high pH values (8 for calcium and 12 for phosphate) and concentrations (500 mM for calcium and 37.5 mM for phosphate). The novel diffusion system is proposed to play an important role in both studying the process of biological mineralization and synthesizing calcium phosphates in different forms.     

Reduced Bone Mineral Density and Bone Metabolism in Aquaporin-1 Knockout Mice

An overt phenotype of aquaporin-1 knockout(AQP1 ko) mice is growth retardation, suggesting possible defects in bone development and metabolism. In the present study, we analyzed the bone mineral density(BMD), bone calcium and phosphorus contents, and bone metabolism in an AQP1 ko mouse model. The BMD of femurs in AQP1 ko mice was significantly lower than that of litter-matched wildtype mice as measured by dual energy X-ray absorptiometry. Consistently, the contents of bone total calcium and phosphorus were also significantly lower in AQP1 ko mice. The reduced BMD caused by AQP1 deficiency mainly affect male mice. Bone metabolic activity, as indicated by 99mTc-MDP absorption measurements, was remarkably reduced in AQP1 ko mice. These results provide the first evidence that AQP1 play an important role in bone structure and metabolism.     

不同月经周期乳腺增生的超声图像分析

本文对不同月经周期乳腺增生的超声图像特征进行了分析。研究对象为选取2017年6月~2019年6月本院乳腺增生患者102例,所有患者均于不同月经周期(月经期、增殖期、分泌期)给予彩色多普勒超声检查,并检测性激素[雌二醇(E2)、孕酮(P)],分析不同月经周期乳腺增生的超声图像特征。结果显示,102例乳腺增生患者中,彩色多普勒超声诊断符合98例,符合率为96.08%,与病理结果比较,差异无统计学意义(P>0.05);乳腺增生患者增殖期乳腺腺体层厚度、导管宽度、乳房胀痛率、E2水平均明显高于月经期、分泌期,增殖期P水平明显低于分泌期但明显高于月经期,差异有统计学意义(P<0.05),分泌期乳腺腺体层厚度、导管宽度、乳房胀痛率、E2水平均高于月经期,但差异无统计学意义(P>0.05)。本文证实了彩色多普勒超声对乳腺增生具有良好的诊断价值,且不同月经周期乳腺增生的超声图像特征存在差异,可有效评价患者月经周期与性激素、增生性病变的关系。     

Calcification mechanism and bony bonding studies of calcium carbonate and composite aluminosilicate/calcium phosphate applied as biomaterials by using radioactivation methods

Bony grafts are used as a filling biomaterial for defective bone. The introduction of new range of synthetic materials offers to surgeons additional possibilities to avoid virus transmission risks by using natural grafts in bony surgery. In this work, two materials, synthetic calcium carbonate and composite aluminosilicate/calcium phosphate were synthesized by an original method and experimented “in vivo” as biomaterials for bony filling. Extracted biopsies were studied by several physico chemical and biological methods. The aim was to evaluate the kinetic resorption and bioconsolidation of these materials. We focused on the bioconsolidation between implant and bone by realising cartographies from the implant to the bone and on the calcification mechanism by determination of the origin of Ca and Sr responsible of the neo-formed bone. Neutron activation analysis (NAA), radiotracers ⁴⁵Ca* and ⁸⁵Sr* and proton-induced X-ray emission (PIXE) were used. Concerning the synthetic calcium carbonate, results show that twelve months after implantation, the mineral composition of implant becomes similar to that of the mature bone. The neoformed bone is composed with Ca and Sr coming from the organism when the Ca and Sr of the implant were progressively eliminated. Concerning the composite geopolymer/calcium phosphate, PIXE and histological studies reveal the intimate links between the bone and the implant starting with the first month after implantation.     

用镱离子和邻苯二酚紫定性定量检测人体尿液和血清中的无机磷酸根

用摩尔比为2∶1的YbCl3和邻苯二酚紫, 在pH=7.0的HEPES缓冲溶液中, 定性、定量检测人体尿液和血清中的无机磷酸根. 随着尿液或经过处理后血清液的加入, 在UV-Vis吸收光谱上, 由623 nm的最大吸收峰逐渐向444 nm的最大吸收峰转移, 同时体系的颜色由蓝变黄. 该体系对尿液和血清中的无机磷酸根相对其它成分显示了很好的选择性. 测得健康人尿液和血清中无机磷酸根的平均含量分别为23.25和1.14 mmol/L, 测定结果与无机磷酸根正常释放基本吻合.