A dynamic simulation of bisphenol A dosimetry in neuroendocrine organs

2004 ◽  
Vol 20 (1-5) ◽  
pp. 29-40 ◽  
Author(s):  
Joseph C Hutter ◽  
Hoan My Luu ◽  
Chung S Kim
Keyword(s):  
Bisphenol A ◽  
Time Course ◽  
Systemic Circulation ◽  
The Body ◽  
Rapid Decline ◽  
Tissue Uptake ◽  
Hydrophobic Compounds ◽  
Neuroendocrine Organs ◽  
Oral Doses

Bisphenol A (BPA) is a known xenoestrogen with similar properties to 17b-estradiol. BPA and estrogen are hydrophobic compounds, and this affects the pharmacokinetics of both compounds in mammals. In a previous study we measured the distribution of BPA in female F344 rats exposed to oral doses of 0.1, 10 and 100 mg/kg. The results showed distribution to target neuroendocrine organs at all doses tested. Using these results, we developed a pharmacokinetic model to predict the dynamic uptake and excretion of BPA by various routes of exposure (po, iv, sc, ip). The model was able to simulate the entire time course (48 h) following various routes of exposure in rats over the dose ranges tested. The model indicated that the ultimate tissue uptake of BPA was established by the rapid initial transfer of free BPA into tissues. After free BPA enters the systemic circulation, metabolism and excretion reactions cause a relatively short duration and rapid decline. This period is followed by a slower long-term decline characteristic of BPA’s biphasic pharmacokinetics. Plasma protein and tissue binding reactions established the long-term half-life of BPA in the body. Route differences in tissue uptake were directly related to the competition between transfer and binding reactions during the absorption phase.

Effect of high intra-alveolar O2 tensions on pulmonary circulation in perfused lungs of dogs

1965 ◽  
Vol 208 (1) ◽  
pp. 130-138 ◽  
Author(s):  
G. J. A. Cropp
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Time Course ◽  
Systemic Circulation ◽  
The Body ◽  
Arterial Blood ◽  
Pulmonary Parenchyma ◽  
Pulmonary Arterial

The resistance to blood flow in the pulmonary circulation of dogs (PVR) increased when their lungs were ventilated with 95–100% oxygen and were perfused with blood that recirculated only through the pulmonary circulation; the systemic circulation was perfused independently. This increase in PVR occurred even when nerves were cut or blocked but was abolished by inhaled isopropylarterenol aerosol. Elevation of intra-alveolar Po2 without increase in pulmonary arterial blood Po2 was sufficient to increase pulmonary vascular resistance. The pulmonary venules or veins were thought to be the likely site of the constriction. These reactions were qualitatively similar to those produced by injection of serotonin or histamine into the pulmonary circulation. The time course of the response and failure to obtain it when the blood was perfused through the remainder of the body before it re-entered the pulmonary circulation are compatible with a theory that high intra-alveolar O2 tension activates a vasoconstrictor material in the pulmonary parenchyma.

scholarly journals Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lise Verbruggen ◽  
Lindsay Sprimont ◽  
Eduard Bentea ◽  
Pauline Janssen ◽  
Azzedine Gharib ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Therapeutic Potential ◽  
Negative Impact ◽  
Chronic Administration ◽  
Systemic Circulation ◽  
The Body ◽  
Ample Evidence ◽  
Anti Inflammatory ◽  
First Time

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system xc− in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported. Whereas for the treatment of the main indications, SAS needs to be cleaved in the intestine into the anti-inflammatory compound mesalazine, it needs to reach the systemic circulation in its intact form to allow inhibition of system xc−. The higher plasma levels of intact SAS (or its metabolites) might induce adverse effects, independent of its action on system xc−. Some of these effects have however been attributed to system xc− inhibition, calling into question the safety of targeting system xc−. In this study we chronically treated system xc− - deficient mice and their wildtype littermates with two different doses of SAS (160 mg/kg twice daily or 320 mg/kg once daily, i.p.) and studied some of the adverse effects that were previously reported. SAS had a negative impact on the survival rate, the body weight, the thermoregulation and/or stress reaction of mice of both genotypes, and thus independent of its inhibitory action on system xc−. While SAS decreased the total distance travelled in the open-field test the first time the mice encountered the test, it did not influence this parameter on the long-term and it did not induce other behavioral changes such as anxiety- or depressive-like behavior. Finally, no major histological abnormalities were observed in the spinal cord. To conclude, we were unable to identify any undesirable system xc−-dependent effect of chronic administration of SAS.

Distribution of bisphenol A in the neuroendocrine organs of female rats

2004 ◽  
Vol 20 (1-5) ◽  
pp. 41-50 ◽  
Author(s):  
CS Kim ◽  
PP Sapienza ◽  
IA Ross ◽  
W Johnson ◽  
HMD Luu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bisphenol A ◽  
Pituitary Gland ◽  
Partition Coefficients ◽  
Female Rats ◽  
Fischer 344 ◽  
Neuroendocrine Organs ◽  
Oral Doses ◽  
The Brain

The distribution of 14C-bisphenol A (BPA) in plasma and neuroendocrine organs was determined in Fischer 344 female rats following three oral doses (0.1, 10 or 100 mg/kg). Plasma and tissue maximum concentrations (Cmax) were reached within 15-30 min of dosing. Plasma areas-under-the-curve (AUC) ranged from 0.06 to 53.9 mg-h/mL. The AUCs of the pituitary gland and uterus/gonads were 16-21% higher than that of plasma. The AUCs of hypothalamus and the rest of the brain were 43.7% and 77% of the plasma AUCs, respectively. In the brain tissue, the exposure increased linearly with the oral dose, as the dose was increased from 0.1 to 10 and 100 mg/kg; the exposure in the brain relative to the plasma increased by factors of 1, 1.19 and 1.24. This indicates that the brain barrier systems do not limit the access of the lipophilic BPA to the brain. The increases of the uterus/gonads relative to the plasma were 1, 1.07 and 1.04. Tissue partitioning was also examined in vitro by the uptake of 14C-BPA. The BPA tissue/blood partition coefficients were as follows: heart, 7.5; liver, 6.1; kidney, 6.4; fat, 3.6; muscle, 2.6; breast, 3.6; ovaries, 9.1; uterus, 5.9; stomach, 5.1; and small intestine, 6.7. The tissue/cerebrospinal fluid partition coefficients were as follows: pituitary gland, 12.8; brain stem, 6.1; cerebellum, 6.4; hippocampus, 7.1; hypothalamus, 6.1; frontal cortex, 4.9; and caudate nucleus, 6.8.

Effects of background adaptation on the pituitary and plasma concentrations of some pro-opiomelanocortin-related peptides in the rainbow trout (Salmo gairdneri)

1984 ◽  
Vol 101 (3) ◽  
pp. 277-284 ◽  
Author(s):  
K. T. Rodrigues ◽  
J. P. Sumpter
Keyword(s):  
Rainbow Trout ◽  
Time Course ◽  
Plasma Concentrations ◽  
Colour Change ◽  
The Body ◽  
Salmo Gairdneri ◽  
White Background ◽  
Black And White ◽  
Background Adaptation

ABSTRACT Radioimmunoassays for α-MSH, β-MSH, ACTH and endorphin were used to measure pituitary concentrations of these peptides in rainbow trout during adaptation to black and white backgrounds. There was no difference in the pituitary content of any of these peptides between long-term black- and white-adapted trout. Plasma levels of α-MSH immunoreactivity were significantly higher in black-adapted trout than in white-adapted trout. Time-course studies revealed that although the body colour of trout showed an initial rapid adaptation to background colour, this was not paralleled by a corresponding change in plasma α-MSH levels. These only showed significant changes after 7 or more days of background adaptation, when melanophore recruitment or degradation occurred on black or white backgrounds respectively. Intravenous administration of mammalian α-MSH, salmon β-MSH I or antibodies to these peptides did not affect short-term background adaptation. However, long-term administration of mammalian α-MSH via osmotic minipump maintained melanophore numbers in grey-adapted trout transferred to a white background, although this observation was based on only two fish. It is concluded that peptides derived from pro-opiomelanocortin do not appear to be involved in controlling physiological colour change but may be involved in regulating morphological colour change of the rainbow trout. J. Endocr. (1984) 101, 277–284

scholarly journals NIS in non-thyroidal tissues and impact on thyroid cancer therapy

2021 ◽  
Author(s):  
Sissy M Jhiang ◽  
Jennifer A Sipos
Keyword(s):  
Thyroid Cancer ◽  
Adverse Effects ◽  
Time Course ◽  
Thyroid Tissue ◽  
Nasolacrimal Duct ◽  
The Body ◽  
Therapeutic Interventions ◽  
Iodide Uptake ◽  
The Past

Radioiodine (131I) has been used to ablate thyroid tissue not removed by surgery or to treat differentiated thyroid cancer that has metastasized to other parts of the body for the past 80 years. However, the Na+/I- symporter (NIS), which mediates active iodide uptake into thyroid follicular cells, is also expressed in several non-thyroidal tissues. This NIS expression permits 131I accumulation and radiation damage in these non-target tissues, which accounts for the adverse effects of radioiodine therapy. We will review the data regarding the expression, function, and regulation of NIS in non-thyroidal tissues. We will explain the seemingly paradoxical adverse effects induced by 131I: the self-limited gastrointestinal adverse effects in contrast to the permanent salivary dysfunction that is seen after 131I therapy. We propose that prospective studies are needed to uncover the time-course of pathological processes underlying development and progression or ultimate resolution of 131I-induced salivary ductal obstruction and nasolacrimal duct obstruction. Finally, preventive measures and early therapeutic interventions that can be applied potentially to eliminate or alleviate long-term radioiodine adverse effects will be discussed.

Gut microbiome a promising target for management of respiratory diseases

2020 ◽  
Vol 477 (14) ◽  
pp. 2679-2696
Author(s):  
Riddhi Trivedi ◽  
Kalyani Barve
Keyword(s):  
Respiratory Diseases ◽  
New Technology ◽  
Bacterial Flora ◽  
Systemic Circulation ◽  
The Body ◽  
Lung Pathology ◽  
Promising Target ◽  
Current Therapies ◽  
Intestinal Microbial Flora ◽  
On Chip

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

Defining the Competence of Psychologists with a View to Public Accountability *

1997 ◽  
Vol 2 (4) ◽  
pp. 293-300 ◽  
Author(s):  
Ype H. Poortinga ◽  
Ingrid Lunt
Keyword(s):  
Scientific Knowledge ◽  
Professional Training ◽  
Professional Competence ◽  
Codes Of Ethics ◽  
The Body ◽  
The European Union ◽  
Rigorous Evaluation ◽  
Judicial Proceedings ◽  
Psychological Knowledge

In national codes of ethics the practice of psychology is presented as rooted in scientific knowledge, professional skills, and experience. However, it is not self-evident that the body of scientific knowledge in psychology provides an adequate basis for current professional practice. Professional training and experience are seen as necessary for the application of psychological knowledge, but they appear insufficient to defend the soundness of one's practices when challenged in judicial proceedings of a kind that may be faced by psychologists in the European Union in the not too distant future. In seeking to define the basis for the professional competence of psychologists, this article recommends taking a position of modesty concerning the scope and effectiveness of psychological interventions. In many circumstances, psychologists can only provide partial advice, narrowing down the range of possible courses of action more by eliminating unpromising ones than by pointing out the most correct or most favorable one. By emphasizing rigorous evaluation, the profession should gain in accountability and, in the long term, in respectability.

Influence of stable iodine on the uptake of the thyroid – model vs. experiment

2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber
Keyword(s):  
Time Course ◽  
Compartment Model ◽  
The Body ◽  
Iodine Uptake ◽  
Model Calculations ◽  
Physiological Conditions ◽  
Iodine Supply ◽  
Predicted Values ◽  
The Individual ◽  
Stable Iodine

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

STUDIES IN THE SUPPOSED GOITROGENOUS EFFECT OF TAP WATER IN HELSINKI

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 630-636
Author(s):  
F.-E. Krusius ◽  
P. Peltola
Keyword(s):  
Tap Water ◽  
Physiological Saline ◽  
Normal Weight ◽  
The Body ◽  
Iodine Uptake ◽  
Redistilled Water ◽  
Detectable Difference ◽  
Term Administration ◽  
Long Term Experiment

ABSTRACT The study reported here was performed in order to examine the tap water of Helsinki for its alleged goitrogenous effect. In a short-term, 24-hour experiment with rats, kept on an iodine-poor diet, we noticed no inhibition of the 4-hour 131I uptake, as compared with that of animals receiving physiological saline instead of tap water. Two similar groups of rats receiving 1 and 2 mg of mercazole in redistilled water showed a distinct blockage of the 4-hour uptake, which proved the effect of this substance. In a long-term experiment of 5 weeks' duration there was no detectable difference in the body weight, thyroid weight and the 4-hour 131I uptake when the rats receiving tap water or distilled water to which 0.45 per cent of sodium chloride was added were compared with each other. Replacement of tap water by a 10 mg per cent solution of mercazole in redistilled water enlarged the thyroid to double its normal weight and increased the 131I uptake to approximately five times that of the controls. Thus our experiments failed to demonstrate any goitrogenous effect in the tap water of Helsinki. Changes similar to those produced by a long-term administration of mercazole, i. e. an enlargement of the thyroid and an increased thyroidal iodine uptake, have been shown to be due to milk collected from goitrous areas. The observations here reported confirm the importance of milk in the genesis of the goitre endemia of Helsinki. Attention is further called to the fact that a thyroidal enlargement combined with an increased thyroidal iodine uptake cannot always be taken as a sign of iodine deficiency because similar changes may be produced by the administration of goitrogens.

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