scholarly journals Studies on the effects of dietary zinc dose on 65Zn absorption in vivo and on the effects of Zn status on 65Zn absorption and body loss in young rats

1987 ◽  
Vol 57 (1) ◽  
pp. 35-44 ◽  
Author(s):  
D. E. Coppen ◽  
N. T. Davies
Keyword(s):  
Gel Filtration ◽  
Male Rats ◽  
Whole Body ◽  
Gel Chromatography ◽  
Zn Content ◽  
Zn Status ◽  
Higher Doses ◽  
Obvious Relation ◽  
Second Peak

1. Weanling male rats were maintained on diets containing 5, 10, 20, 40, 80 or 160 mg zinc/kg for 14 d. On day 15 they received 65Zn either by intraperitoneal injection or in a test meal containing 20 mg Zn/kg. After dosing, the rats were again maintained on the diets they had received previously.2. Whole-body 65Zn retention was measured immediately after dosing and daily for a further 9 d. From regression analysis of the semi-logarithmic plots of 65Zn retention from 0 to 192 h after 65Zn administration, the true extent of 65Zn absorption and the biological half-life (t1/2) of body 65Zn stores were calculated.3. At the end of the experiment, the rats were killed and the entire small intestines of some rats from each group were rapidly flushed out to remove food and faecal residues, frozen in liquid nitrogen and stored under an atmosphere of N2 at –20° before separation of cytosolic Zn-binding fractions by gel filtration on Sephadex G–75.4. The results suggest that rats which received diets that were either deficient(5 mg Zn/kg), marginal (10 mg Zn/kg) or adequate (20–80 mg Zn/kg) in Zn achieved homeostatic regulation of body Zn by changes in both the extent of Zn absorption and excretion. However, when Zn supply was excessive, increasing from 80 to 160 mg Zn/kg, no further changes were seen in Zn absorption, and homeostatic control appeared to be effected entirely by changes in rates of body Zn loss.5. Gel chromatography of intestinal cytosol on Sephadex G-75 revealed that Zn was associated with two major fractions. The first (peak 1) had a molecular weight (MW) > 75 kdaltons and the second (peak 2), a MW of approximately 10 kdaltons and was assumed to be metallothionein.6. There was no obvious relation between the amount of Zn bound to peak 1 and dietary Zn content. In contrast, the amount of Zn recovered in peak 2 increased linearly with increasing dietary Zn content.7. Comparisons between the effect of dietary Zn content on Zn bound to peak 2 and 65Zn retention may, depending on the range of Zn intakes, indicate possible roles for intestinal metallothionein in the control of Zn absorption or excretion.8. A study of the effects of dietary dose of 65Zn on the extent of 65Zn absorption in rats of normal Zn status indicated a possible biphasic relation. At low doses (5–40 mg Zn/kg) 65Zn absorption appeared to exhibit a curvilinear response to increasing 65Zn dose, indicating possibly a saturable process. At higher doses (40–160 mg Zn/kg) the capacity of this process appeared to be exceeded and 65Zn absorption increased in a linear fashion.

PURIFICATION OF "INHIBIN" FROM HUMAN OVARIAN FOLLICULAR FLUID

1979 ◽  
Vol 90 (1) ◽  
pp. 157-166 ◽  
Author(s):  
S. Chari ◽  
C. R. N. Hopkinson ◽  
E. Daume ◽  
G. Sturm
Keyword(s):  
Follicular Fluid ◽  
Polyacrylamide Gel Electrophoresis ◽  
Gel Filtration ◽  
Deae Cellulose ◽  
Exchange Chromatography ◽  
Male Rats ◽  
Acetone Powder ◽  
Gel Chromatography ◽  
Apparent Homogeneity ◽  
Ovarian Follicular Fluid

ABSTRACT Following the earlier demonstration of inhibin-like activity in human ovarian follicular fluid a method for its purification to apparent homogeneity is described. The fluid was converted to acetone powder and subjected sequentially to ammonium sulphate fractionation, gel chromatography on Sephadex G-200, continuous gradient ion-exchange chromatography on DEAE-cellulose, first with a pH gradient from 8.0 to 4.0 and then with a NaCl gradient to 1 m at pH 5.2. The active fraction from this step was subjected to gel filtration on Sephadex G-100 and finally passed through an Amicon Centriflo membrane CF-25 (cut off point: 25 000 m.w.). The ultrafiltrate was homogeneous by SDS-polyacrylamide gel electrophoresis, had a molecular weight of the order of 23 000 and was capable of suppressing serum gonadotrophin levels in the castrated male rats in as low a dose as 25 μg/rat.

Blood-brain barrier penetration of [14C]darolutamide compared with [14C]enzalutamide in rats using whole body autoradiography.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 345-345 ◽  
Author(s):  
Christian Zurth ◽  
Steffen Sandmann ◽  
Dagmar Trummel ◽  
Dietrich Seidel ◽  
Hille Gieschen
Keyword(s):  
Blood Brain Barrier ◽  
Early Time ◽  
The Body ◽  
Brain Barrier ◽  
Male Rats ◽  
Whole Body ◽  
Post Dose ◽  
Whole Body Autoradiography ◽  
Blood Brain

345 Background: Darolutamide (ODM-201) (Daro) is an investigational oral and high-affinity androgen receptor antagonist. In preclinical studies, penetration of Daro through the blood–brain barrier (BBB) is negligible and in a retrospective safety analysis of the ARADES database for CNS-related adverse events (AEs), only 1 report of urinary incontinence was linked to Daro (Fizazi K, et al. 2015). Various clinical trials on enzalutamide (Enza) have reported CNS AEs (eg, seizure, falls, fatigue, pain). To understand the differences in CNS outcomes, we report an in vivo tissue distribution study with [14C]-labelled Enza and Daro in a head-to-head study in rats by means of quantitative whole-body autoradiography (QWBA). Methods: Male rats were orally dosed with 10 mg/kg [14C]Daro or [14C]Enza in the same formulation, administration volume, and radioactive dose. The animals were sacrificed at each drug’s specific tmax (time to reach the maximum concentration) in blood and brain and processed for QWBA. Results: At early time points [14C]Daro- and [14C]Enza-derived radioactivity was rapidly absorbed from the gastrointestinal tract and homogenously distributed throughout the body. By 8 h post dose, [14C]Daro was significantly eliminated from almost all organs/tissues, whereas [14C]Enza remained constant within the body. In contrast to [14C]Daro, high and persistent radioactivity was observed in brain for [14C]Enza. At tmax, the brain/blood-ratio of [14C]Enza was ~0.765, while [14C]Daro was about 10-fold lower at ~0.074. Conclusions: Results show that post dose, there was a 10-fold lower BBB penetration of [14C]Daro compared with [14C]Enza. At 8 h, [14C]Daro was rapidly eliminated and almost undetectable in all tissues, including brain, in contrast to [14C]Enza that remained constant. These data suggest that Daro might have a lower risk of inducing CNS-related AEs than Enza. Further clinical studies are ongoing.

Comparison of somatostatin-28 and somatostatin-14 clearance by the perfused rat liver

1985 ◽  
Vol 63 (1) ◽  
pp. 62-67 ◽  
Author(s):  
M. Seno ◽  
Y. Seino ◽  
Y. Takemura ◽  
S. Nishi ◽  
H. Ishida ◽  
...  
Keyword(s):  
Rat Liver ◽  
Gel Filtration ◽  
Perfused Rat Liver ◽  
Half Time ◽  
Hepatic Extraction Ratio ◽  
Plasma Extract ◽  
Second Peak ◽  
Somatostatin 14

The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 ± 0.0051 min−1, 36.6 ± 7.6 min, 0.34 ± 0.08 mL/min, and 17.2 ± 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 ± 0.0022 min−1, 17.3 ± 1.0 min, 0.71 ± 0.05 mL/min, and 35.4 ± 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-28 to SS-14 in vivo, the plasma disappearance of 2 μg SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 ± 0.12 min in the whole rat, significantly shorter than the 2.20 ± 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed. These results suggest that SS-28 is cleared by the rat liver in vivo and in vitro and that it is cleared more slowly than SS-14. Furthermore, we find that little, if any, conversion of SS-28 to SS-14 occurs in the liver.

Molecular Size Distribution of Fibrinogen Derivatives Formed in Vitro and in Vivo: a Chromatographic Study

1976 ◽  
Vol 36 (01) ◽  
pp. 014-026 ◽  
Author(s):  
M. B Donati ◽  
R Verhaeghe ◽  
D. E Culasso ◽  
J Vermylen
Keyword(s):  
Biological Fluids ◽  
Gel Filtration ◽  
Molecular Size ◽  
Gel Chromatography ◽  
Chromatographic Study ◽  
Elution Volume ◽  
Human Fibrinogen ◽  
Elution Pattern

SummaryUsing gel chromatography, fibrinogen derivatives present in purified systems or in biological fluids were separated and partially characterized. Eight groups of fibrinogen derivatives could be separated by gel filtration through 6% agarose in large columns, four with an elution volume smaller and four groups with an elution volume larger than that of fibrinogen. Careful calibration of the column allowed estimation of the diffusion coefficients of some of the derivatives and, thus, comparison with derivatives previously identified. Three, rather than two, groups of intermediate derivatives were observed during the degradation of human fibrinogen by plasmin in vitro or in vivo. One of these had a marked tendency to polymerize.A rather distinct difference in elution pattern was found between plasma obtained during streptokinase administration and from patients with intravascular coagulation.

Inhalation Toxicity and Genotoxicity of Hydrofluorocarbon (HFC)-236fa and HFC-236ea

2000 ◽  
Vol 19 (2) ◽  
pp. 69-83 ◽  
Author(s):  
William J. Brock ◽  
David P. Kelly ◽  
Susan M. Munley ◽  
Karin S. Bentley ◽  
Kathy M. McGown ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Human Lymphocytes ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Seminiferous Tubules ◽  
Inhalation Toxicity ◽  
Male And Female ◽  
Male And Female Rats

The acute, subchronic, and developmental and genetic toxicity of hydrofluorocarbon (HFC)-236fa and HFC-236ea were evaluated to assist in establishing proper handling guidance. In acute inhalation studies, rats were exposed whole body for 4 hours to various concentrations of each isomer. Based on the lack of mortality, the approximate lethal concentration for HFC-236ea for male rats was > 85,000 ppm. For HFC-236fa, the LC50 for males and females (combined) was > 457,000 ppm. Narcotic-like effects, e.g., prostration, incoordination, and reduced motor activity, were observed only during exposure to either isomer, but were not evident after termination of exposure. In cardiac sensitization studies, HFC-236ea induced cardiac sensitization at ≥ 35,000 ppm, with fatal responses occurring at 50,000 ppm and greater. For HFC-236fa, a cardiac sensitization response was observed at 150,000 ppm and greater but not at 100,000 ppm. A fatal cardiac sensitization response was observed in one dog exposed to 150,000 ppm HFC-236fa. In 90-day subchronic inhalation studies, male and female rats were exposed whole body to HFC-236ea at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. Similarly, male and female rats were exposed whole body to HFC-236fa at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. During exposure, narcotic-like effect (reduced acoustic startle response) was observed at 50,000 ppm with both isomers, although there appeared to be an adaptive response to this effect as the study progressed. With HFC-236ea, dilatation of the seminiferous tubules, without effects on germ or Sertoli cells, was observed only in rats at 50,000 ppm. No other effects on in-life measures or on clinical or anatomic pathology, including histopathology, were observed for either isomer. In rat developmental toxicity studies, no evidence of embryotoxicity or teratogenicity was observed with either isomer exposed up to 50,000 ppm during gestational days 7 to 16. Also, no developmental toxicity was observed in rabbits exposed to HFC-236fa at concentrations of up to 50,000 ppm during gestational days 7 to 19. Neither of the HFC-236 isomers was mutagenic in the Ames reverse mutation assay or clastogenic in the chromosomal aberration assay with human lymphocytes. No increase in chromosomal aberrations was observed in in vivo micronucleus studies with either isomer.

scholarly journals Feedback regulation of granulopoiesis: polymerization of lactoferrin abrogates its ability to inhibit CSA production

Blood ◽  
1982 ◽  
Vol 60 (1) ◽  
pp. 108-112 ◽  
Author(s):  
GC Jr Bagby ◽  
RM Bennett
Keyword(s):  
Tissue Culture ◽  
Culture Medium ◽  
Feedback Regulation ◽  
Tissue Culture Medium ◽  
Mononuclear Leukocytes ◽  
Gel Chromatography ◽  
Polymeric Form ◽  
Higher Doses

Neutrophil extracts were prepared from the peripheral blood of 40 normal volunteers and tested for their ability to inhibit CSA production by mononuclear leukocytes. Highly dilute neutrophil extracts inhibited CSA production/release, while extracts selectively depleted of lactoferrin by antibody affinity chromatography did not. In addition, higher concentrations of neutrophil extracts and higher doses of lactoferrin (10(-9)-10(-6) M) failed to inhibit CSA production/release. We found no evidence of CSA or CSA-enhancing factors in either our lactoferrin or our neutrophil extracts. However, using gel chromatography and rate zonal density sedimentation, we noted that lactoferrin undergoes concentration-dependent polymerization at 10(-9)-10(-10) M in tissue culture medium and that while monomeric lactoferrin effectively inhibits CSA production/release in vitro, the polymeric form does not. Thus, while we have confirmed that lactoferrin is the activity in neutrophil extracts that inhibits CSA production, we have also found that lactoferrin undergoes reversible polymerization at physiologic concentrations and that the polymerized molecule is inactive. The tendency of lactoferrin to polymerize in tissue culture medium and in vivo should be taken into account in any studies on its potential role as a physiologically relevant regulator of granulopoiesis.

scholarly journals Isolation and partial characterization of an acid phosphatase from Artemisia vulgaris pollen extract

2002 ◽  
Vol 67 (8-9) ◽  
pp. 567-572 ◽  
Author(s):  
Tanja Cirkovic-Velickovic ◽  
Marija Gavrovic-Jankulovic ◽  
Mirjana Bukilica ◽  
Ljuba Mandic ◽  
Spomenka Petrovic ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Gel Filtration ◽  
Sulfhydryl Group ◽  
Inhibitory Effect ◽  
Tween 20 ◽  
Pollen Extract ◽  
Gel Chromatography ◽  
Artemisia Vulgaris ◽  
Nitrophenyl Phosphate

An acid phosphatase from an extract of mugwort (Artemisia vulgaris) pollen was purified by a factor of 48 by a combination of ion exchange and gel-chromatography. The molecular weights of the enzyme were 76 kDa and 73 kDa, determined by gel filtration on a Sephadex G-100 sf column and by SDS PAGE(under reducing and non-reducing conditions), respectively. In analytical isoelectrofocusing, the enzyme appears as two very close bands pI at about 4.2. The optimum pH for the enzyme is 5.4. The apparent Km for p-nitrophenyl phosphate was estimated to be 0.16mM. The purified enzyme has broad specificity, and hydrolyses p-nitrophenyl phosphate and ?-naphthyl phosphate. Pyrophosphate and O-phospho-L-tyrosine were estimated to be the best substrates for this enzyme as potential in vivo substrates. The enzyme is inhibited competitively by phosphate (Ki = 1.25 mM), molybdate (Ki = 0.055 mM) and pyrophosphate (Ki = 6.7 mM) and non-competitively by fluoride (Ki = 9.8 mM). Metal ions such as Hg2+, Cu2+ and Zn2+ express an inhibitory effect on the enzyme, while the enzyme is slightly activated by non-ionic detergents, Tween 20 and Triton X-100. There is no change in the enzyme activity in the presence of tartrate, citrate, EDTA, 1,10-phenanthroline and sulfhydryl-group modifiers such as p-chloromercuribenzoate and N-ethylmaleimide.

scholarly journals Feedback regulation of granulopoiesis: polymerization of lactoferrin abrogates its ability to inhibit CSA production

Blood ◽  
1982 ◽  
Vol 60 (1) ◽  
pp. 108-112 ◽  
Author(s):  
GC Jr Bagby ◽  
RM Bennett
Keyword(s):  
Tissue Culture ◽  
Culture Medium ◽  
Feedback Regulation ◽  
Tissue Culture Medium ◽  
Mononuclear Leukocytes ◽  
Gel Chromatography ◽  
Polymeric Form ◽  
Higher Doses

Abstract Neutrophil extracts were prepared from the peripheral blood of 40 normal volunteers and tested for their ability to inhibit CSA production by mononuclear leukocytes. Highly dilute neutrophil extracts inhibited CSA production/release, while extracts selectively depleted of lactoferrin by antibody affinity chromatography did not. In addition, higher concentrations of neutrophil extracts and higher doses of lactoferrin (10(-9)-10(-6) M) failed to inhibit CSA production/release. We found no evidence of CSA or CSA-enhancing factors in either our lactoferrin or our neutrophil extracts. However, using gel chromatography and rate zonal density sedimentation, we noted that lactoferrin undergoes concentration-dependent polymerization at 10(-9)-10(-10) M in tissue culture medium and that while monomeric lactoferrin effectively inhibits CSA production/release in vitro, the polymeric form does not. Thus, while we have confirmed that lactoferrin is the activity in neutrophil extracts that inhibits CSA production, we have also found that lactoferrin undergoes reversible polymerization at physiologic concentrations and that the polymerized molecule is inactive. The tendency of lactoferrin to polymerize in tissue culture medium and in vivo should be taken into account in any studies on its potential role as a physiologically relevant regulator of granulopoiesis.

Cardioprotective Effects of Diet with Different Grains on Lipid Profiles and Antioxidative System in Obesity-Induced Rats

2012 ◽  
Vol 82 (2) ◽  
pp. 85-93 ◽  
Author(s):  
Y. Kim ◽  
H. Shin ◽  
S. Lee
Keyword(s):  
Aortic Wall ◽  
Plasma Lipids ◽  
Antioxidant Activities ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Lipid Profiles ◽  
Dietary Lipids ◽  
Male Rats

In the present study, the nutritional quality of four grains including adlay (AD), buckwheat (BW), glutinous barley (GB), and white rice (WR) were evaluated in terms of plasma lipid parameters, gut transit time, and thickness of the aortic wall in rats. The rats were then raised for 4 weeks on the high-fat diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1 % cholesterol and 20 % dietary lipids. Forty male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. The level of thiobarbituric acid-reactive substances (TBARS) in liver was shown to be higher in rats by the order of those fed WR, AD, GB, and BW. This indicates that other grains decreased oxidative stress in vivo more than WR. The superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase levels in the AD, BW, and GB groups were significantly higher than those in the WR group (p < 0.05). Plasma lipid profiles differed significantly according to grain combination, and decreased aortic wall thickness was consistent with the finding of decreased plasma low-density lipoprotein cholesterol (LDL-C) (p < 0.05) and increased high-density lipoprotein (HDL-C) in rats fed AD, BW, and GB (p < 0.001). The antioxidant and hypolipidemic capacities of grains are quite high, especially those of adlay, buckwheat, and glutinous barley. In conclusion, this study has demonstrated that the whole grains had a cardioprotective effect. This effect was related to several mechanisms that corresponded to lowering plasma lipids, decreasing TBARS, and increasing antioxidant activities.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

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