Potency of peroral and parenteral administration of Zinc-DTPA for decorporation of 241Am from the gastrointestinal tract

An effect of cincacine at three doses (25, 150 and 300 mumol/kg) has been studied in rats receiving 241Am citrate intragastrically. The radionuclide was introduced every other day for 2 weeks. The total content was 925 kBq/kg. A cincacine administration leads to limitation of radionuclide accumulation in the major organs of deposition independent of the modes of intake. At gastrointestinal 241Am intake peroral cincacine administration is more effective in limiting this radionuclide accumulation in skeleton but less effective in reduction of its accumulation in liver compared to parenteral cincacine. No reliable dependence of cincacine efficacy on dosage has been revealed. A morphology study of organs has shown that cincacine ingestion at a dose of 150 mumol/kg for 4 weeks and at a dose of 300 mumol/kg for 2 weeks produces a toxic effect on the small intestine mucosa. 25 mumol/kg is the optimum dose and per os administration of higher doses is not expedient.     

Study of the influence of peroral zincacin on the removing of ingested Americium

Effect of different cincacine doses was studied in rats ingesting americium citrate during 2 weeks. As a result new data showing the possibility and efficacy of per oral cincacine administration at americium intake into digestive tract have been obtained. Dose dependence of cincacine efficacy has been stated for per oral 241Am intake. Preparation administration at a dose of 25 mumol/kg reduces amount of 241Am in skeleton, liver and kidney by 93, 90 and 33%, respectively and is optimum for radionuclide removal from the body and for the prevention of its deposition in organs. Digestive system organs and kidney structure at cincacine administration at a dose of 150 and 300 mumol/kg) to the rats ingesting 241Am have been studied.     

Combined prophylactic administration of riboxin and algisorbum at 239Pu intake into gastrointestinal tract of rats

The present study is devoted to the investigation of effectiveness of combined prophylactic administration of riboxin and algisorbum at 239Pu per oral intake and possible mechanisms of their interaction, and also to comparative estimation of effectiveness of combined administration of the preparations at per oral and intra peritoneal methods of riboxin introduction. The experiments have been carried out on white nonlinear rats. Riboxin (per oral and intra peritoneal) and algisorbum (per oral) have been introduced to the rats both separately and combined before per oral 239Pu introduction. Data obtained as a result of the investigation showed that combined riboxin and algisorbum introduction into gastrointestinal tract before 239PU intake lead to greater decrease in the plutonium content in the organs of deposition than single algisorbum administration. Intra peritoneal riboxin introduction reduced effectiveness of per oral algisorbum administration in plutonium binding in GI tract. Efficiency of combined riboxin and algisorbum administration in the reduction of 239Pu accumulation in organs depends on the method of riboxin introduction and develops only at per oral introduction.     

Absorption from the gastrointestinal tract of rats of biologically incorporated 241Am found in fish

In experiments on mongrel albino rats it was shown that the absorption of 241Am "biologically incorporated" in fish from the gastrointestinal tract amounted to 0.1% and exceeded by 4.5 times the intake of 241Am nitrate and by 6 times the absorption of 241Am administered in fish externally contaminated with americium 241.     

Effect of gavaged chemical form of 241Am on its retention in mice

The retention of 241Am in mice 48 h after administration by gavage is reported here. The 241Am was given to mice in the form of either 241Am nitrate or 241Am citrate. The 241Am was also injected into rats in the same form. The homogenized livers of those rats were subsequently administered by gavage to another group of mice. The retention of 241Am citrate was 1.5 X 10(-2)% of the original dose and was the highest among the compounds examined. The retention of biologically incorporated 241Am into the liver as 241Am nitrate and as 241Am citrate was 2.4 X 10(-3) and 2.6 X 10(-3)%, respectively, and was similar to the retention of 241Am nitrate, which was 2.8 X 10(-3)%. The ratio of the retention in the carcass to that in the liver for the 241Am citrate was lower than that of the 241Am nitrate and the biologically incorporated 241Am. This difference indicates that the distribution of 241Am in the animal body depends on the chemical form administered. The retention of liver-incorporated 241Am as citrate after autolysis of the liver is similar to that of fresh liver-incorporated 241Am citrate.     

Prevalence of Candida albicans in patients receiving total parenteral nutrition

The prevalence of Candida albicans was quantitatively compared in 74 surgical patients during and after total parenteral nutrition (TPN). Suppression of oral food intake is probably responsible for the decrease of the C. albicans population in the mouth. On the contrary anal swabs were more often positive for C. albicans during TPN. This may be due to local conditions as was observed in a group of patients who were not given TPN but were also immobilized for a long period.     

Absorption of 241Am in the gastrointestinal tract

In experiments with rats a study was made of a number of factors influencing the resorption of 241Am from the gastrointestinal tract (GIT). The resorption of 241Am from GIT was found to be 120-245 times more intensive in neonatal rats, during the first 21 days after birth (a milk diet), than in adult animals. A milk diet for adult rats produced a 5-fold increase in the resorption of 241Am from GIT. The additional administration of digestive enzymes, as a homogenate from pancreas and small intestine, produced a 7--9-fold increase in the rate of 241Am resorption from GIT.     

Toxicity of 241Am in male C57BL mice: relative risk versus 226Ra

A life-span study on male C57BL mice after injection of various doses of 241Am was conducted. The effects on life span were evaluated and the incidence of tumors was determined by procedures that take competing risks into account. Bone tumors were induced in the mice by injections of 22 and 58 Bq 241Am per g. The mice died early from nonneoplastic diseases at the higher dose levels (190, 373, and 1197 Bq 241Am/g). Additionally, spontaneously occurring tumors such as liver carcinomas, lymphosarcomas, and lymphoreticulosarcomas occurred at an enhanced rate with increasing dose level. The data for survival time after 241Am injection and death with bone tumor were compared to data collected previously for 226Ra-injected mice of the same C57BL strain. This enabled direct comparison in the same strain of the effects of the bone-surface seeker 241Am to the effects of the bone-volume seeker 226Ra. The proportional hazards model was applied and the rate of death with bone tumor was 12.9 +/- 5.2 times higher after 241Am injection than after 226Ra injection if the regression covariate was the average dose to the skeleton. The relative risk was 3.5 +/- 1.7 if regressed on the injected radioactivity. The mortality rate after 241Am injection was 20.4 +/- 3.6 times higher than after 226Ra injection if regressed on average dose to the skeleton.     

Chelation therapy of incorporated plutonium-238 and americium-241: comparison of LICAM(C), DTPA and DFOA in rats, hamsters and mice

The carboxylated catechoylamide 3,4,3-LICAM(C) was tested for removal of 238Pu and 241Am from small laboratory rodents. The effectiveness of treatment was compared with that of two ligand preparations approved for clinical use: calcium-trisodium diethylenetriaminepentaacetate (DTPA) and desferrioxamine (DFOA). With early treatment and at the dosage used clinically for the decorporation of actinides with DTPA (30 mumol/kg body weight) LICAM(C) was superior to DFOA but when compared with DTPA, the effect of LICAM(C) on 238Pu was greater only in bone; as little as 1 mumol LICAM(C)/kg was as effective as 30 mumol DTPA/kg. However, in all animals treated with LICAM(C) there was a large increase in the 238Pu content of the kidney. With 241Am the effect of DTPA was always superior to that of LICAM(C). The best overall results early (1 day) after injection of 238Pu and 241Am were achieved by a combination of a single injection of LICAM(C) and DTPA with subsequent continuous administration of DTPA in drinking water. LICAM(C) affected the retention of 238Pu even if given orally; the data suggested that about 3 per cent of ingested LICAM(C) was absorbed. When the beginning of treatment was delayed, LICAM(C) became equally effective or less effective than DTPA even as far as 238Pu retention in bone was concerned, but it still increased the accumulation of 238Pu in the kidneys.     

Gastrointestinal absorption of americium-241 by orally exposed swine: comparison of experimental results with predictions of metabolic models

Two groups of 11-week-old swine (40 miniature and 40 domestic swine) received a single oral administration of 1.9 X 10(8) Bq (5.2 mCi) of 241Am citrate, and groups of eight animals, four of each type, were killed and sampled at 1, 2, 4, 8, 16, 24, 48, 72, and 96 h and 30 days later. Uptake and excretion patterns of the radioactivity appeared to occur in three phases: rapid uptake, rapid excretion, and then a slower excretion. All animals were systematically dissected, and the eviscerated carcasses were autoclaved for separation of bone and muscle. The predominant site of deposition was bone, and autoclaving had little effect on releasing 241Am from either bone or muscle. The maximum fractional gastrointestinal absorption of 1.1 X 10(-3) occurred 8 h after radionuclide administration. The tissue distribution data suggest partitions of 50, 20, and 30%, for bone, liver, and other soft tissues, respectively. Two metabolic models were evaluated: a modified Mewhinney-Griffith model and the ICRP 30 model to compare the biological data with model predictions. All models underestimated the actual early time data, but the fits to the experimental results were better at later times.     

Quantitative patterns of a model of intratracheal administration in an experiment

The distribution of 239PuO2 (241Am) and BeO (7BeO) within the lungs of rats and dogs after the intratracheal administration was found to follow a normal law. The amplitude of deposition variations reached 98 per cent of the amount administered. It is recommended to group the experimental animals by individual deposition estimates.     

IGF-I treatment facilitates transition from parenteral to enteral nutrition in rats with short bowel syndrome

The goal of growth factor treatment in patients with short bowel syndrome (SBS) is to facilitate transition from parenteral to enteral feedings. Ideal use of growth factors would be acute treatment that produces sustained effects. We investigated the ability of acute insulin-like growth factor I (IGF-I) treatment to facilitate weaning from total parenteral nutrition (TPN) to enteral feeding in a rat model of SBS. After a 60% jejunoileal resection + cecectomy, rats treated with IGF-I or vehicle were maintained exclusively with TPN for 4 days and transitioned to oral feeding. TPN and IGF-I were stopped 7 days after resection, and rats were maintained with oral feeding for 10 more days. In IGF-I-treated rats, serum concentration of IGF-I and final body weight were significantly greater because of a proportionate increase in carcass lean body mass than in vehicle-treated rats. Acute IGF-I treatment induced sustained jejunal hyperplasia on the basis of significantly greater concentrations of jejunal mucosal protein and DNA without a change in histology or sucrase activity. These results demonstrate that acute IGF-I facilitates weaning from parenteral to enteral nutrition in association with maintenance of a greater body weight and serum IGF-I concentration in rats with SBS.     

The effect of age on the distribution of 241Am in the rat body

In experiments with albino mongrel rats aged from 2 weeks to 1.5-2 years, the kinetics of 241Am distribution was studied after single intraperitoneal administration thereof. The content of 241Am in the skeleton was shown to decrease and in the liver to increase with age.     

Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles

Decorporation of intravenously injected monomeric 241Am and 237+239Pu by the administration of 30 mumole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles). 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% of the injected activity (corrected for radioactive decay) to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% of the injected activity (corrected for radioactive decay) for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the time period.     

Oral estrogen masculinizes female zebra finch song system

It is well established that parenteral treatment of female zebra finch chicks with estradiol masculinizes their song control nuclei and that as adults they are capable of song. Concern over the widespread use of putative environmental estrogens caused us to ask whether oral exposure to estrogens (a natural route of exposure) could produce similar effects. We dosed chicks orally with estradiol benzoate (EB; 1, 10, 100, and 1000 nmol/g of body mass per day, days 5-11 posthatch), the non-ionic surfactant octylphenol (100 and 1000 nmol/g), or the pesticides methoxychlor (100 and 1000 nmol/g) and dicofol (100 nmol/g) and measured their song control nuclei as adults. EB treatment produced increases in song nuclei comparable to that induced by parenteral administration of estrogens. This is the first study of which we are aware to use an oral route of administration, which simulates the natural process of parent birds feeding their nestlings. We conclude that oral exposure to estradiol alters song control nuclei and we report in a related paper (Millam et al., 2001) that such exposure severely disrupts reproductive performance. Although we detected no influence of xenobiotics on induction of song control nuclei the possibility remains that oral exposure to xenoestrogens in high enough doses could affect development.     

Humoral and cellular responses to native antigen following oral and parenteral immunization with lipid-conjugated bovine serum albumin

Humoral and cellular immune responses of rabbits to bovine serum albumin (BSA) were measured following oral and parenteral immunization with either BSA or one of two dodecanoic acid conjugates of BSA. The first consisted of a mixture of lightly and heavily conjugated BSA-molecules (L-BSA-mix), while the second (L-BSA) was a homogeneous preparation of heavily conjugated BSA with more than 95% of the 60 available amino groups covalently bound to dodecanoic acid. Animals ingesting L-BSA-mix had a similar humoral immune response but enhanced cellular reactivity to BSA in comparison to animals ingesting the native antigen. No systemic immunologic responses to BSA were detected following ingestion of L-BSA in spite of the demonstration of circulating BSA antigenic groups. This lack of a detectable immune response after oral administration was not due to masking of antigenic sites by the lipid residues since both humoral and cellular immune responses to BSA were obtained in animals injected with L-BSA. Ingestion of L-BSA did not induce tolerance since a subsequent injection of BSA elicited a normal primary immune response. The differences in immunogenicity between BSA, L-BSA and L-BSA-mix following oral administration may be related to different modes of antigen recognition by the gut-associated lymphoid tissues.     

Radiosensitivity and proliferative activity of vertebral CFU-S surviving in mice injected with oncogenic activities of 239Pu or 241Am

Survival, radiosensitivity and capability to produce differentiated progeny were followed in CFU-S from lumbar vertebrae of mice injected with 198.6 kBq 239Pu/kg or 208.6 kBq 241Am/kg. The CFU-S assay and 59Fe uptake into spleen colonies were used. The number of CFU-S from treated mice was significantly lower than in controls. Higher radiosensitivity of CFU-S from 239Pu- or 241Am-treated mice was demonstrated using additional exposure to 0.5 Gy X-rays 1, 24, 48, 72 hrs after cell transplantation and expressed more precisely by survival curves obtained 1 hr after the marrow cell injection. The effect of 239Pu on CFU-S was characterized by Do 0.58 Gy (n = 0.91) and that of 241Am by Do 0.64 Gy (n = 0.91); corresponding control values were Do 0.89 Gy, n = 1.11. Lower iron utilization due not only to the decreased CFU-S numbers, but also to the defective production of erythroid cells per one CFU-S was found. Complexity of radiation effect on hemopoietic stem cells was demonstrated by the present study.     

Administration of antiprogestin J956 for contraception in bears: a pharmacological study

Effective and reversible control of reproduction in bears is highly desirable for conservation and management programs in zoos to establish genetically variable ex-situ populations of bears within the constraints of limited space in captivity. The reproductive physiology of bears is characterized by two main traits--seasonality and delayed implantation, which is progesterone dependent. This offers the opportunity to interrupt early pregnancy by short-term administration of antiprogestins. The aim of the present study was to investigate the pharmacological characteristics of antiprogestin J956 to establish an efficient contraceptive protocol for administration of J956 in captive bears. The J956 binds to the uterine progesterone receptor of bears (n = 2) with almost the same relative binding affinity (1.25) as progesterone. The blood serum level of J956 after oral (on four consecutive days) and single parenteral administration was determined by a modified progestin receptor assay. The relative bioavailability of J956 after oral administration was approximately 10% of the parenteral administration. The estimated half-life was 12 to 16 hours after oral administration. Parenteral treatment of J956 (10 mg/kg body mass) led to sustain plasma concentrations (6.4 +/- 1.3 ng/mL) in one black bear and in five brown bears. The plasma level lasted for almost 2 months. Oral and low dosage parenteral (1 mg/kg body mass) administration of J956 had no effect on ongoing pregnancies in bears. Whereas single parenteral administration with higher dosages of J956 (7.5 to 10 mg/kg body mass) efficiently prevented implantation of early embryos in eight female captive bears.     

Comparative assessment of the danger of inhaling 239Pu and 241Am based on the degree of leukopenia in dogs

From the analysis of the results of examination of 96 dogs it is concluded that the estimate of a relative danger of breathing transuranium radionuclides with different metabolism rates (polymeric 239Pu and monomeric 241Am), according to degree of leukopenia is more reliable when it is compared with a mean weighed dose per whole organism than the dose per individual "critical" organ.     

Local immunity in the parenteral immunization of guinea pigs with a ribosomal dysentery vaccine

After immunization of guinea pigs with Shigella sonnei ribosomal vaccine O-antibodies appeared not only in the blood serum of the animals, but also in their lacrimal fluid. Since no correlation between the levels of serum and secretory antibodies was detected and since the time course of changes in these antibody levels was quite different (serum antibodies reached their peak on day 7 while secretory antibodies, on day 14 after vaccination), antibodies in lacrimal fluid were supposed to reflect local immune response induced by parenteral administration of ribosomal vaccine, irrespective of systemic immune response. The peak of secretory O-antibodies coincided in time with the period of the highest protection of guinea pigs from Shigella keratoconjunctivitis. The animals with a high level of secretory antibodies were better protected from Shigella infection than those with a low level of secretory antibodies. These data suggest that locally produced O-antibodies play an important role in protective immunity induced by parenteral administration of the ribosomal vaccine.