Anionic and cationic exchange mechanisms in the skin of anurans, with special reference to Leptodactylidae in vivo

In several species of anurans, the in vivo skin has been shown to absorb Na + and Cl - independently from dilute external solutions. That the mechanism for sodium absorption is different from that of chloride absroption is born out by the following: (1) Either of these ions is absorbed without an accompanying ion when this latter is impermeant. (2) From NaCl solutions there can be an unequal absorption of sodium and chloride. (3) A selective inhibition of the absorption of one of the ions can be produced experimentally, while the net flux of the other remains unchanged. In all these situations, the absorbed ion has to be exchanged against an endogenous ion of the same charge. In Calyptocephalella gayi , H + and HCO - 3 are exchanged against sodium and chloride respectively. A comparison of the relationships between H + excretion and Na + absorption in vivo skins and shortcircuited in vitro skins shows that in the latter no H + excretion occurs, only the Na + transport being maintained under these experimental conditions. From this, one must conclude that the active Na + transport is the motive factor of the transport mechanism. H + excretion by the in vivo skin plays the role of physiologically short-circuiting the Na + transport.

2021 ◽  
pp. 1-9
Author(s):  
Etsuo Niki

Reactive oxygen and nitrogen species have been implicated in the onset and progression of various diseases and the role of antioxidants in the maintenance of health and prevention of diseases has received much attention. The action and effect of antioxidants have been studied extensively under different reaction conditions in multiple media. The antioxidant effects are determined by many factors. This review aims to discuss several important issues that should be considered for determination of experimental conditions and interpretation of experimental results in order to understand the beneficial effects and limit of antioxidants against detrimental oxidation of biological molecules. Emphasis was laid on cell culture experiments and effects of diversity of multiple oxidants on antioxidant efficacy.


2003 ◽  
Vol 71 (8) ◽  
pp. 4297-4303 ◽  
Author(s):  
B. Villarreal-Ramos ◽  
M. McAulay ◽  
V. Chance ◽  
M. Martin ◽  
J. Morgan ◽  
...  

ABSTRACT Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), and it has the potential to induce disease in humans. CD8+ T cells (CD8 cells) have been shown to respond to mycobacterial antigens in humans, cattle, and mice. In mice, CD8 cells have been shown to play a role in protection against mycobacterial infection. To determine the role of CD8 cells in bovine TB in vivo, two groups of calves were infected with the virulent M. bovis strain AF2122/97. After infection, one group was injected with a CD8 cell-depleting monoclonal antibody (MAb), and the other group was injected with an isotype control MAb. Immune responses to mycobacterial antigens were measured weekly in vitro. After 8 weeks, the animals were killed, and postmortem examinations were carried out. In vitro proliferation responses were similar in both calf groups, but in vitro gamma interferon (IFN-γ) production in 24-h whole-blood cultures was significantly higher in control cattle than in CD8 cell-depleted calves. Postmortem examination showed that calves in both groups had developed comparable TB lesions in the lower respiratory tract and associated lymph nodes. Head lymph node lesion scores, on the other hand, were higher in control calves than in CD8 cell-depleted calves. Furthermore, there was significant correlation between the level of IFN-γ and the head lymph node lesion score. These experiments indicate that CD8 cells play a role in the immune response to M. bovis in cattle by contributing to the IFN-γ response. However, CD8 cells may also play a deleterious role by contributing to the immunopathology of bovine TB.


Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 957-966
Author(s):  
P Pootrakul ◽  
A Christensen ◽  
B Josephson ◽  
CA Finch

The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.


1960 ◽  
Vol XXXIII (I) ◽  
pp. 59-66 ◽  
Author(s):  
J. van der Vies

ABSTRACT Adrenal function in rats under various experimental conditions was studied by incubating the adrenals in vitro and determining the corticosteroid output during one hour. This in vitro corticoid production was reduced after hypophysectomy, hypothalamus-lesioning and treatment with hydrocortisone or with Nembutal and morphine. On the other hand, an increased production was observed following stimulation of the pituitary-adrenal system by exogenous histamine or corticotrophin. From these experiments it is concluded that the corticoid production in vitro reflects the activity of the adrenal cortex in vivo and hence can be used for the study of the latter function.


2002 ◽  
Vol 22 (11) ◽  
pp. 1377-1398 ◽  
Author(s):  
Yiyun Huang ◽  
Dah-Ren Hwang ◽  
Raj Narendran ◽  
Yasuhiko Sudo ◽  
Rano Chatterjee ◽  
...  

The recent introduction of a number of new radiotracers suitable for imaging the serotonin transporters (SERT) has radically changed the field of SERT imaging. Whereas, until recently, only one selective SERT radiotracer was available ([11C]McN 5652) for SERT imaging with positron emission tomography (PET), several new C-11-labeled radiotracers of the N,N-dimethyl-2-(arylthio)benzylamine class have been described as appropriate imaging agents for the SERT. The aim of this study was to conduct a comparative evaluation of four of the most promising agents in this class ([11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM) with the reference tracer [11C]McN 5652 under standardized experimental conditions. This evaluation included in vitro measurements of affinity and lipophilicity, and in vivo PET imaging experiments in baboons. In vitro, DASB displayed significantly lower affinity for SERT than the other four tracers. In the blood, [11C]DASB and [11C]AFM display faster clearance and higher free fractions. Brain uptake was analyzed with kinetic modeling using a one-tissue compartment model and the metabolite-corrected arterial input function. The kinetic uptake of [11C]DASB was significantly faster compared with the other compounds, and the scan duration required to derive time-independent estimates of regional distribution volumes was shorter. [11C]DAPA exhibited the slowest brain kinetic. Regional-specific-to-nonspecific equilibrium partition coefficient (V3“) was the highest for [11C]AFM, followed by [11C]DASB and [11C]DAPA, which in turn provided higher V3” values than [11C]ADAM and [11C]McN 5652. From these experiments, two ligands emerged as superior radiotracers that provide a significant improvement over [11C]McN 5652 for PET imaging of SERT: [11C]DASB, because it enables the measurement of SERT availability in a shorter scanning time, and [11C]AFM, because its higher signal-to-noise ratios provide a more reliable measurement of SERT availability in brain regions with relatively low density of SERT, such as in the limbic system.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5525-5525
Author(s):  
David Dingli ◽  
Kah-Whye Peng ◽  
Mary E. Harvey ◽  
Sompong Vongpunsawad ◽  
Elizabeth R. Bergert ◽  
...  

Abstract Background: Viral vectors based on the Edmonston strain of measles virus (MV-Edm) selectively destroy all tumor cell lines tested in vitro. The oncolytic activity of the virus is enhanced by expression of the thyroidal sodium iodide symporter (MV-NIS) that allows selective 131I uptake by infected tumor cells and eliminates myeloma tumor xenografts that are resistant to the parent virus. MV-NIS is being considered for therapy of patients with relapsed or refractory multiple myeloma. Advanced myeloma is associated with significant immunosuppression with the potential risk of uncontrolled virus proliferation. The number of agents with activity against MV is limited. Low energy (Auger) electrons have a short path length and selectively damage cells in which the isotope decays. Thus, we hypothesized that the Auger electron emitting isotope 125I, selectively taken up by cells expressing NIS, can be used to control viral proliferation. Methods: A replication competent MV that expressed both a soluble form of carcinoembryonic antigen (CEA) and NIS (MV-NICE) was rescued and characterized. Cells were infected with MV-NICE or control vectors and exposed to 125I with appropriate controls. CEA expression and viral titers were determined at different time points. The role of free radical generation on virus replication was explored. In vivo control of MV-NICE replication with 125I was attempted. Results: MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Extracellular decay of the isotope has no effect on virus proliferation. Auger electron damage is in part mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment. Conclusion: MV-NICE does not replicate faster in the presence of radiation under our experimental conditions. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.


Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 957-966 ◽  
Author(s):  
P Pootrakul ◽  
A Christensen ◽  
B Josephson ◽  
CA Finch

Abstract The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.


2020 ◽  
Vol 13 (10) ◽  
pp. 265
Author(s):  
Alexey Goltsov ◽  
Maciej Swat ◽  
Kirill Peskov ◽  
Yuri Kosinsky

The kinetic model of Prostaglandin H Synthase-1 (PGHS-1) was developed to investigate its complex network kinetics and non-steroidal anti-inflammatory drugs (NSAIDs) efficacy in different in vitro and in vivo conditions. To correctly describe the complex mechanism of PGHS-1 catalysis, we developed a microscopic approach to modelling of intricate network dynamics of 35 intraenzyme reactions among 24 intermediate states of the enzyme. The developed model quantitatively describes interconnection between cyclooxygenase and peroxidase enzyme activities; substrate (arachidonic acid, AA) and reducing cosubstrate competitive consumption; enzyme self-inactivation; autocatalytic role of AA; enzyme activation threshold; and synthesis of intermediate prostaglandin G2 (PGG2) and final prostaglandin H2 (PGH2) products under wide experimental conditions. In the paper, we provide a detailed description of the enzyme catalytic cycle, model calibration based on a series of in vitro kinetic data, and model validation using experimental data on the regulatory properties of PGHS-1. The validated model of PGHS-1 with a unified set of kinetic parameters is applicable for in silico screening and prediction of the inhibition effects of NSAIDs and their combination on the balance of pro-thrombotic (thromboxane) and anti-thrombotic (prostacyclin) prostaglandin biosynthesis in platelets and endothelial cells expressing PGHS-1.


1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 517-519 ◽  
Author(s):  
Agostino Fracasso ◽  
Lorenzo Calo ◽  
Silvano Landini ◽  
Paolo Morachiello ◽  
Flavio Righetto ◽  
...  

The role of plasticizers (PLS) in inducing water flow inhibition and peritoneal sclerosis has been demonstrated in both In vivo and In vitro studies. Interleukin-1 (IL-1) has been shown to be a regulator of fibroblast proliferation as well as collagenase production. The aim of this study was to evaluate the role of PLS in stimulating mononuclear ce1l1L-1 secretion. Two cultures containing 103 cells/mL were obtained from 14 healthy subjects. One was used as the control, and the other was mixed with diethylhexylphthalate (DEHP) to reach a final concentration of 2.8x10” M. After 4 hours the samples were centrifuged, and the supernatants were tested by radioimmunoassay for IL-1α and IL-1β. The results showed a significant increase In both IL-1α and IL-1 β production In DEHP-stimulated cells in comparIson to the controls: 42.6±15.4 versus 29.3±10 ng/L (p<0.015) for IL-1α. and 153.6±55 versus 113.6±32 ng/L (p<0.03) for IL-1β In conclusion, PLS added to mononuclear cells were able to Induce IL-1 secretion. This mechanism could be responsible, at least in part, for the development of peritoneal sclerosis. Thus the employment of plasticlzer-free bags should be elective in peritoneal dialysis.


Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 1689-1697 ◽  
Author(s):  
V. M. Navarro ◽  
J. M. Castellano ◽  
R. Fernández-Fernández ◽  
S. Tovar ◽  
J. Roa ◽  
...  

Abstract KiSS-1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, namely kisspeptins, which acting through the G protein-coupled receptor GPR54 are able to inhibit tumor progression. Unexpectedly, a reproductive facet of this newly discovered system has recently arisen, and characterization of the role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion has been initiated. However, such studies have been so far mostly restricted to LH, and very little is known about the actual contribution of this system in the regulation of FSH release. To address this issue, the effects of KiSS-1 peptide on FSH secretion were monitored in vivo and in vitro under different experimental conditions. Intracerebroventricular administration of KiSS-1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED50 value for the FSH-releasing effects of KiSS-1 of 400 pmol, i.e. approximately 100-fold higher than that of LH. In addition, systemic (ip and iv) injection of KiSS-1 significantly stimulated FSH secretion in vivo. However, KiSS-1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, mechanistic studies revealed that the ability of KiSS-1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, our results extend previous recent observations on the role of KiSS-1 in the control of LH secretion and provide solid evidence for a stimulatory effect of KiSS-1 on FSH release, acting at central level. Overall, it is proposed that the KiSS-1/GPR54 system is a novel, pivotal downstream element in the neuroendocrine network governing gonadotropin secretion.


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