Differential induction of bone and hematopoietic tumors in C3H mice after the injection of 239Pu citrate

Although alpha-emitting plutonium is easily distributed in the skeleton via circulation and subsequently induces bone tumors, there is little evidence that hematopoietic neoplasias are highly induced even though bone marrow stem cells are irradiated internally by alpha particles. We injected groups of female C3H strain mice with doses of 239Pu citrate from 500 to 10000 Bq to investigate the dose-related spectrum of tumor types induced during a lifetime. Survival time was reduced strikingly in all the injected mice due to much earlier induction of bone and lymphoid tumors as compared to the control animals that showed a variety of soft tissue tumors after a longer period of survival. Induction of osterosarcomas was dose-dependent, being maximal in 70% of the animals that received a mean skeletal dose of 10 Gy or less, but was 48% or less at 20 Gy or more. Non-thymic lymphomas accompanied by lymphocytic leukemia were observed in only 4-6% of the animals that received a dose of 10 Gy or less whereas it was maximal in 17-19% at 20 Gy or more. In contrast, there were no bone tumors in the control animals, rather thymic lymphomas or histiocytic lymphomas were found very late in 20% and other soft tissue tumors, including lung, liver and ovary tumors, were noted in 60%. Neither myeloid leukemia nor other myelogenous neoplasias were found in the control and 239Pu-injected animals that received a mean skeletal dose of 3 Gy or more. These results indicate that the differential induction of bone tumors and hematopoietic tumors in mice depends on the dose range and the time after the injection of plutonium.     

DNA fragmentation in rat brain after intraperitoneal administration of kainate

Cell death occurs in many neuropathological conditions. However, the mechanisms governing this process(es) remain generally unknown. In this report we studied whether excitotoxic neuronal death evoked by kainic acid (KA) in rat brain is associated with ladder-like DNA fragmentation. DNA was isolated from hippocampi, entorhinal and sensory cortices at various times following intraperitoneal KA (10 mg kg-1) injections. Typical oligonucleosome-sized DNA fragmentation was observed in all three structures at 18 h and 72 h following KA administration. These findings were further confirmed by in situ nick-translation. DNA fragmentation is believed to be diagnostic for apoptosis. The clear ladders of DNA fragmentation appeared after 18 h, although slight degradation was observed as early as 12 h after KA administration.     

酸性硫脲溶液中金银分离的研究 (Ⅳ)离子交换树脂法

从H_2SO_4—CS(NH_2)—H_2O体系中分离金银的离子交换树脂法,是又一个较好的分离方法.上海744苯乙烯型树脂,对〔Au(SCN_2H_4)~2Ⅰ~+和〔Ag(SCN_2H_4)_3〕~+有很好的吸附性能,其大孔结构特性,更适合对大型配离子团的吸附.论文给出了HCl—Br_2(水)溶液为金的洗提剂;HCl溶液为银的洗提剂.单因素和多因素正交试验研究给出了吸附富集和解吸分离的最优工艺条件.     

Time course of stomach mineralization, plasma, and urinary changes after a single intravenous administration of gadolinium(III) chloride in the male rat

In a previous experiment it was reported that the intravenous administration of gadolinium chloride (GdCl3) to rats results in a discrete band of interstitial mineralization in the fundic glandular mucosa of the stomach. To investigate the time course for the development of this lesion and its relationship to plasma calcium and phosphate concentrations, 2 experiments were carried out in male Sprague-Dawley rats given a single intravenous dose of 0.07 mmol/kg GdCl3. Plasma calcium and phosphate concentrations approximately doubled between 30 min and 12 hr postdose but had regressed back to near normal values by 24 hr. However, there were no observable clinical signs in treated animals. Histologically, there was progressive mineralization of the lamina propria of the neck region of the fundic glands from 6 hr postdose, forming a distinctive mineral band by 12 hr postdose. At 7 and 14 days postdose the mineral deposits were accompanied by mucous cell hyperplasia, interstitial fibrosis, and a very sparse infiltration of inflammatory cells. By 56 days postdose only occasional mineral deposits remained. Transmission electron microscopy showed mineral first nucleated on collagen in the interstitium, but there was no evidence of cell necrosis. X-ray microanalysis showed that the interstitial mineral was composed of calcium and phosphate in the form of hydroxyapatite; gadolinium (Gd) was only very rarely identified. These findings are consistent with metastatic mineralization. The source, cause, and the exact nature of the excess plasma calcium and phosphate are unknown, and the possible significance of this effect for clinical use of Gd-containing chelates in nuclear magnetic resonance imaging requires further investigation.     

Evaluation of peritoneal lavage smears and intraperitoneal administration of anti-neoplastic agents in stage III and IV gastric cancer

Examinations of peritoneal lavage smears (cy) in gastric cancer surgical stages III and IV are very important for determining the disease stage. We have been carrying out these examinations for 8 years. One hundred sixty patients with gastric cancer were examined. The incidence of cy positivity was higher in T4 than in T3, and higher in P1,2,3 than in P0. We performed intraperitoneal administration of CDDP in 10 patients with gastric cancer using a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. No difference in survival was observed between patients who received chemotherapy via i.p. and those who received it i.v.     

Adsorption of Ce（ Ⅳ ） Anionic Nitrato Complexes onto Anion Exchangers and Its Application for Ce （Ⅳ） Separation from Rare Earths （ Ⅲ ）

Ceriumis one of the cheapest[1]and most abun-dant rare earths (RE) .However ,high purityis usual-ly required for its utilization in industry , where it isusedfor sulfur control insteels ,pyrophoric alloys ,ce-ramic ,catalyst support ,polishing powders ,etc .In its minerals ,as well as in the spent nuclearfuel ,ceriumis accompanied by other RE.They basi-cally exist in solution as stable RE(Ⅲ) species ,which makes their mutual separation rather difficult .In contrast to other RE, Ce(Ⅲ) can…     

Within-subject variability in cocaine pharmacokinetics and pharmacodynamics after intraperitoneal compared with intravenous cocaine administration.

Performance in rats (Rattus norvegicus) was measured on a differential reinforcement of low-rate schedule (DRL 45-s) in 1.5-hr sessions after 2 mg/kg intravenous (IV) or 10–20 mg/kg intraperitoneal (IP) cocaine administration, with each dose given twice and separated by 3–5 days. For successive IV doses, cocaine effects were similar, with minimal within-subject variability. For IP cocaine, the effects were not always similar; performance was variable and sometimes remained at baseline level. These diminished effects occurred following either the 1st or 2nd IP injection. A parallel pharmacokinetic study of cocaine confirmed that within-subject variability existed in cocaine concentration-time profiles after IP cocaine, and that a low serum cocaine concentration-time profile could account for the diminished effects. The IP route for cocaine administration should be used with caution. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo disposition of p-substituted phenols in the young rat after intraperitoneal and dermal administration

The objective of this study was to examine the 120-hr disposition of phenol and four p-substituted congeners after ip and dermal administration in the 29-day-old female rat. The dermal absorption was very high (66-80% of the dose) for phenol, cyanophenol, heptyloxyphenol and nitrophenol, but minimal for hydroxybenzoic acid (2%). The major portion of the dose for all of the phenols not absorbed dermally in 24 hr was washed from the skin. Only minor amounts (1-2%) were detected in the treated skin at 120 hr. Urinary excretion was the predominant means of elimination for these phenols and occurred primarily within 24 hr after dermal and ip administration. However, the excretion of heptytoxyphenol after administration by both routes differed from that of the other compounds, with more of it detected in the faeces. The profile of metabolites in urine (collected at 12-24 hr) from the animals dermally treated with phenol, cyanophenol, heptyloxyphenol and nitrophenol showed only peaks that eluted earlier than the parent compound, which suggests that conjugates or more polar metabolites were formed and excreted. The difference in dermal absorption between hydroxybenzoic acid and the other phenols may be due to potential ionization of the p-substituted carboxylic acid group of hydroxybenzoic acid. This suggests that, at least for the phenols examined in this study, physicochemical characteristics other than just lipophilicity can affect in vivo dermal absorption.     

Circulatory kinetics of intravenously injected 238Pu(IV) citrate and 14C-CaNa3-DTPA in mice: comparison with rat, dog, and reference man

New ligands for in vivo chelation of Pu(IV) are being synthesized and evaluated in mice for efficacy and toxicity. Biokinetic studies of the new ligands, CaNa3-DTPA, and Pu(IV) are major components of those investigations. Young adult female mice were injected intravenously (iv) with 3H-inulin, 14C-CaNa3-DTPA, or 238Pu(IV) citrate to provide baseline data for plasma clearance, tissue uptake, and excretion rates and to determine the dilution volume (VOD) and renal clearance rate (RC) of filterable substances. Published plasma clearance data for iv-injected 14C-CaNa3-DTPA and Pu(IV) citrate in Reference Man, dog, and rat were collected. Based on combined data for 3H-inulin and 14C-CaNa3-DTPA, VOD = 17% of body weight and RC = 18 mL kg(-1) min(-1) for mice. Retention of 14C-CaNa3-DTPA in the four species is proportional to body weight and inversely proportional to RC: Integrals of the retention of 14C-CaNa3-DTPA from R(t) = 1.0 to R(t) = 0.05 are 108, 43, 28, and 10 DF min, respectively, for Reference Man, dog, rat, and mouse. Clearances of iv-injected Pu(IV) citrate from plasma are in the same order: The plasma curve integrals from injection to 1440 min are 840, 640, 280, and 67 DF min, respectively, for Reference Man, dog, rat, and mouse. In mice, a large fraction of newly injected Pu(IV) is rapidly transferred to the interstitial water of bulk soft tissue (excluding liver and kidneys), from which it is cleared at the same rate as from the plasma. Rapid plasma clearance, escape into interstitial water (22%ID at 20 min), significant early urinary excretion (8%ID in 12 h), and prompt deposition in liver and skeleton (complete in 12 h) are evidence of inefficient binding to plasma protein (mainly transferrin) of newly injected Pu(IV) in mice. Conversely, slow plasma clearance, little early urinary excretion, and delayed deposition in liver and skeleton reflect more efficient binding by transferrin of newly injected Pu(IV) in Reference Man and dog. Pharmacokinetic parameters (effective dosage, effective concentration) of CaNa3-DTPA, alone or combined with plasma Pu(IV) integrals, yielded only qualitative predictions of the relative efficacies of CaNa3-DTPA therapy in four species. The need for improved models of Pu(IV) and ligand biokinetics and the suitability of the three animals for predicting chelation therapy outcomes in humans are discussed.     

Perturbation in the 240Pu/239Pu global fallout ratio in local sediments following the nuclear accidents at Thule (Greenland) and Palomares (Spain)

Diabetes complicates 2-3% of all pregnancies and is associated with an increase in both perinatal morbidity and mortality, though reasons for these adverse outcomes are unknown. Estrogen biosynthesis is a critical factor during pregnancy and is carried out in the placenta via aromatase (cytochrome P450 19A1), which catalyzes the conversion of C-19 androgens to C-18 estrogens. Previous studies have shown that hormones such as insulin-like growth factors and insulin regulate aromatase activity when studied in vitro. Interestingly, levels of these hormones are altered in patients with diabetes. Thus, we hypothesized that the presence of maternal diabetes may alter placental aromatase activity and thus estrogen biosynthesis, possibly serving as one factor in the adverse outcomes of babies born to mothers with diabetes. To this end, we measured the production of 19-hydroxyandrostenedione, 19-oxoadrostenedione and estrone in 30 placental tissues from diabetic patients, using [7-3H]androst-4-ene-3,17-dione as a model substrate for aromatase (P450 19A1). A statistical difference was detected in the percentage of 19-oxoandrostenedione formed between the overt and control groups (P < 0.05). Additionally, NADPH P450-reductase levels were measured in these same tissues to determine whether alterations in this enzyme necessary for aromatase activity could be affected by diabetes. No differences in reductase levels were detected among the patient groups. However, a statistical correlation was found between NADPH P450-reductase activity and the formation velocities of all three estrogen products (P < 0.05). Thus, it appears that the presence of diabetes does not affect placental aromatase activity.     

Recovery of Al(III) and Fe(III) from mixed chloride solutions containing platinum(IV)

The sorption of Fe(III), Al(III) and Pt(IV) from the individual and mixed chloride solution was investigated by using PC88A resin. With the increase of HCl concentration to 5 M, the distribution coefficient of Fe decreased slowly, while that of Al decreased rapidly and the distribution coefficient of Pt was nearly zero in our experimental range. Batch experiments showed that it was possible to extract both Fe and Al simultaneously by adjusting HCl and PC88A resin concentrations. However, continuous extraction chromatographic experiments indicated that simultaneous sorption of Al as well as Fe was difficult in our experimental range. Two extraction chromatographic steps would extract most of Fe and 90% of Al from the mixed solution, while Pt was not extracted. Extraction chromatography of the mixed chloride solution with PC88A resin was found to be fast and simple.     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Accumulation of (-)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues

Absorption of orally administered (-)-epicatechin (EC) in rats was studied to obtain plasma pharmacokinetic profiles of EC metabolites. Rats were administered 172 micromol/kg body weight of EC, and blood was collected from the tail for 8 h after administration. Seven groups of compounds possessing the basic structure of EC were identified by using a combination of enzymatic hydrolysis, HPLC and electron impact mass spectrometry. Metabolites were quantified with a new, simple and sensitive method using HPLC with electrochemical detection. Ingested EC was absorbed from the alimentary tract and was present in the rat common blood circulation in the form of glucuronide and/or sulfate conjugates. The activity of conjugative enzymes in rat tissues was studied. The highest activity of glucuronosyltransferase was found in the intestinal mucosa of both of the small and large intestine; the highest activity of phenolsulfotransferase occurred in the liver, and that of catechol-O-methyl transferase was found in the liver and kidney. It has been proposed that the first detoxification step of dietary EC, namely, glucuronidation, occurs at the level of the intestinal mucosa in rats, and EC enters the common blood circulation exclusively in the glucuronized form. The compound is then sulfated in the liver and methylated in the liver and kidney. Because ingested EC undergoes extensive conjugation, its biological activities previously demonstrated in vitro may not be occurring in in vivo systems.     

Excretion of 35S-Tobias acid (2-naphthylamino, 1-sulphonic acid) by the rat after oral and intravenous administration

The lipid-lowering effects of 3 g of the nicotinic acid derivative pentaerythritoltetranicotinate (niceritrol) given either 1 g X 3 or 1.5 g X 2 have been evaluated in 18 subjects with hyperlipoproteinaemia. When 1 g niceritrol was given three times daily, the serum TG concentration fell from 3.14 +/- 0.48 to 1.86 +/- 0.18 mmol/1 (41% reduction) and the serum cholesterol concentration from 282 +/- 9 to 227 +/- 11 mg/100 ml (20% reduction). The same daily dose, given 1.5 g twice, did not significantly lower the serum TG concentration, and serum cholesterol was lowered by only 12%. Niceritrol tablets prepared with a dissolution time of 60 or 90 min had identical lipid-lowering properties. Although patients may find it practical to take niceritrol only twice daily, such a dose regimen has considerably less effect on elevated serum lipids than a thrice-daily regimen.     

Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration

1. The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.     

Separation of praseodymium(III) from aqueous solutions by nanofiltration

Abstract

The increased demand for rare earth elements in commercial products is increasing their production, which in turn increases public exposure to rare earth elements. The objective of the present work is to study the separation of praseodymium from aqueous solutions by a commercial nanofiltration membrane (NF-300) at various operating conditions. The permeate and feed samples were analysed with inductively coupled plasma atomic emission spectrometry (ICPAES) to find praseodymium [Pr(III)] concentration. The results indicated that the separation of Pr(III) ions increased with increase in applied pressure (2–10 bar) and cross flowrate (4–16 L min^?1); and decreased with increase in feed concentration (10 mg L^?1 PrCl₃ – 100 mg L^?1 PrCl₃). The highest observed separation of the Pr(III) was found to be 89·07 and 84·20% for an initial feed concentration of 10 and 100 mg L^?1 PrCl₃ respectively. It was also observed that separation of Pr(III) increases to 99·28 and 99·30% in complexation step by using ethylene diamine tetra aceticacid (EDTA) and diethylene triamine penta aceticacid (DTPA) respectively, as the chelating agent has generally influenced by pH (2 –10).

La demande accrue d’éléments de terres rares dans les produits commerciaux augmente leur production, ce qui, à son tour, augmente l’exposition du public aux éléments de terres rares. Le but de ce travail est d’étudier la séparation du praséodyme à partir de solutions aqueuses au moyen d’une membrane commerciale de nanofiltration (NF-300) sous diverses conditions d’utilisation. On a analysé les échantillons de perméat et d’apport au moyen de la spectroscopie d’émission atomique avec plasma induit par haute fréquence (ICPAES) afin de déterminer la concentration du praséodyme [Pr(111)]. Les résultats indiquaient que la séparation d’ions de Pr(111) augmentait avec une augmentation de la pression appliquée (2–10 bar) et de la vitesse de l’écoulement transversal (4–16 L min^?1) et diminuait avec une augmentation de la concentration de l’apport (10 mg L^?1 PrCl₃ – 100 mg L^?1 PrCl₃). On a trouvé que la valeur la plus élevée de séparation observée pour le Pr(111) était de 89·07 ou de 84·20% pour une concentration initiale de l’apport de 10 ou de 100 mg L^?1 de PrCl₃, respectivement. On a également observé que la séparation du Pr(111) augmentait jusqu’à 99·28 ou 99·30% dans une étape de complexation en utilisant de l’acide éthylènediaminetétracétique (EDTA) ou de l’acide diéthylènetriamino-pentaacétique (DTPA), respectivement, comme agent chélateur, influencé généralement par le pH (2–10).     

The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2- (3-phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat

The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycerol conjugates was compared with that of non-esterified 3PBA. Three radiolabeled triacylglycerols (rac-1-(3-phenoxy-[ring-14C]-benzoyl)-2,3-dipalmitoylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoylglycerol (2(3PBA)DPG) and the "natural" tri-[1-14C]oleoylglycerol) were incorporated into rat VLDL. Nonesterified 3PBA was prepared in rat serum albumin solution. Each preparation was administered i.v. to rats and serial blood samples were taken during the subsequent 6 hr. Urine and faeces were collected and tissue residues determined at 6 hr and 48 hr after administration. Biphasic elimination of 3PBA was observed with half-lives of 18 min and 2 hr. The triacylglycerols showed a rapid first phase and a longer second phase half-life: trioleoylglycerol 26 hr, 1(3PBA)DPG 7.6 hr and 2(3PBA)DPG 17.3 hr. The majority (63-76%) of 3PBA (whether esterified or not) was eliminated within 24 hr in urine, which contained similar profiles of metabolites. The triacylglycerols gave rise to higher tissue residues than did non-esterified 3PBA, particularly in adipose tissue which alone was not significantly depleted of radioactivity between 6 and 48 hr. The results accord with the rapid association of the VLDL-(3PBA)DPG complexes with lipoprotein lipase of the capillary epithelium, followed by hydrolysis to 3PBA, metabolism and elimination but with a proportion being redistributed into adipose tissue, re-esterified and then eliminated relatively slowly.