scholarly journals Some Effects of Breeding Season and Castration on the Prostate and Epididymis of the Brushtail Possum, Trichosurus vulpecula

1985 ◽  
Vol 38 (3) ◽  
pp. 313 ◽  
Author(s):  
JD Curlewis ◽  
GM Stone
Keyword(s):  
Breeding Season ◽  
Androgen Receptors ◽  
Protein S ◽  
Relative Increase ◽  
Seasonal Effects ◽  
Brushtail Possum ◽  
Secretory Product ◽  
High Concentration ◽  
Low Level

In an attempt to understand the mechanism(s) responsible for the reported marked seasonal increase in prostatic, but not epididymal, weight in T. vulpecula, a number of parameters were measured in tissues from mature, entire males sampled within and outside of the breeding season and from castrates. Conditions for the measurement of cytosol androgen receptors were also established. The weight of both the prostate and the epididymis was significantly elevated in the breeding season but the relative increase in prostate weight was considerably greater. The increase in prostatic weight was associated with a decrease in DNA: g tissue and an increase in protein: DNA and RNA: DNA ratios, each indicative of cellular hypertrophy and/or accumulation of secretory product. In the epididymis there were no significant seasonal changes in RNA: DNA, protein: DNA or DNA: g tissue ratios. Low-capacity, high-affinity binding was demonstrated in the epididymal and prostatic cytosols and values for the equilibrium association constants and receptor concentrations were within the range reported for androgen receptors in eutherian species. The temperature sensitivity of the binding, steroid specificity and slow dissociation in the cold indicated that in both tissues cystosol receptor and not androgen-binding or serum-binding protein(s) were being measured. In prostatic, but not epididymal, cytosol a low level of progesterone binding was observed and was masked by triamcinolone acetonide. When expressed in terms of tissue DNA, cytosol androgen receptor level in the prostate only was elevated in the breeding season. Prostatic tissue showed a low level of 5a-reductase in vitro which was not influenced by season. However, both tissues showed a high concentration of 5a-dihydrotestosterone and in the prostate, where seasonal effects were measured, the concentration was higher in the breeding season. This indicates that although 5a-dihydrotestosterone is the likely active androgen in the prostate it may be formed elsewhere. Part of the explanation for the increased growth of the prostate in the breeding season appears to be a change in receptor concentration coupled with elevated tissue androgen level.

scholarly journals Stem cell factor induction of in vitro murine hematopoietic colony formation by "subliminal" cytokine combinations: the role of "anchor factors"

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 663-669 ◽  
Author(s):  
PA Lowry ◽  
D Deacon ◽  
P Whitefield ◽  
HE McGrath ◽  
PJ Quesenberry
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
The Other ◽  
Proliferative Potential ◽  
High Concentration ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Low Level

Abstract The high levels of hematopoietic growth factors required for in vitro and in vivo activity raise questions as to their role in normal hematopoietic maintenance. We hypothesize that the use of combinations of cytokines to stimulate hematopoietic progenitors might allow individual factors to exert their influence at lower, more physiologically relevant concentrations. Growth factor combinations were assessed by their ability to stimulate both total colonies and high proliferative potential colony-forming cells (HPP-CFC), an early murine hematopoietic progenitor, in double-layer agar cultures. Very- low-level combinations of colony-stimulating factor (CSF)-1, granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin (IL)-1 alpha, and IL-3 had little or no clonogenic capacity. Plateau levels of rr stem cell factor (rrSCF), a c-kit ligand, used alone also had negligible clonogenic capacity, but when combined with the low-level combination of the other five factors produced total colony and HPP-CFC growth approaching that produced by all factors at plateau levels. Delayed addition experiments suggest that this effect may represent sequential activity of SCF and the other factors. We propose a model of the normal hematopoietic microenvironment in which SCF at locally high concentration on the stromal cell surface “anchors” the hematopoietic stem cell's response to multiple other cytokines at physiologically relevant levels.

Stem cell factor induction of in vitro murine hematopoietic colony formation by "subliminal" cytokine combinations: the role of "anchor factors"

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 663-669 ◽  
Author(s):  
PA Lowry ◽  
D Deacon ◽  
P Whitefield ◽  
HE McGrath ◽  
PJ Quesenberry
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
The Other ◽  
Proliferative Potential ◽  
High Concentration ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Low Level

The high levels of hematopoietic growth factors required for in vitro and in vivo activity raise questions as to their role in normal hematopoietic maintenance. We hypothesize that the use of combinations of cytokines to stimulate hematopoietic progenitors might allow individual factors to exert their influence at lower, more physiologically relevant concentrations. Growth factor combinations were assessed by their ability to stimulate both total colonies and high proliferative potential colony-forming cells (HPP-CFC), an early murine hematopoietic progenitor, in double-layer agar cultures. Very- low-level combinations of colony-stimulating factor (CSF)-1, granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin (IL)-1 alpha, and IL-3 had little or no clonogenic capacity. Plateau levels of rr stem cell factor (rrSCF), a c-kit ligand, used alone also had negligible clonogenic capacity, but when combined with the low-level combination of the other five factors produced total colony and HPP-CFC growth approaching that produced by all factors at plateau levels. Delayed addition experiments suggest that this effect may represent sequential activity of SCF and the other factors. We propose a model of the normal hematopoietic microenvironment in which SCF at locally high concentration on the stromal cell surface “anchors” the hematopoietic stem cell's response to multiple other cytokines at physiologically relevant levels.

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 328-333 ◽  
Author(s):  
N J de Fouw ◽  
Y F de Jong ◽  
F Haverkate ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Blood Platelets ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor ◽  
Pai 1

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.

The Anticoagulant Properties of a Modified Form of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Human Neutrophil Elastase ◽  
Factor X ◽  
Sds Page

SummaryProtein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC.In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor X awas inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor X amediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S.These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.

The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

2020 ◽  
Vol 65 (9-10) ◽  
pp. 3-7
Author(s):  
V. V. Gostev ◽  
Yu. V. Sopova ◽  
O. S. Kalinogorskaya ◽  
M. E. Velizhanina ◽  
I. V. Lazareva ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Selection ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Concentration ◽  
Short Term ◽  
High Concentrations ◽  
Selection Of ◽  
Selection Of Resistance ◽  
Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

Cancerous Cell Destruction Using Low Level Ultrasound in the Presence of Gold Nanoparticles: An in vitro Study on 4T1 Cells

2018 ◽  
Vol 14 (4) ◽  
pp. 329-334
Author(s):  
Ahmad Shanei ◽  
Neda Attaran ◽  
Marziyeh Mirzaeiyan ◽  
Mohammad Reza Salamat ◽  
Hossein Hejazi
Keyword(s):  
Gold Nanoparticles ◽  
In Vitro Study ◽  
Vitro Study ◽  
Low Level ◽  
Cell Destruction ◽  
Cancerous Cell ◽  
4T1 Cells

A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben
Keyword(s):  
Systematic Review ◽  
Antioxidant Activity ◽  
Membrane Receptors ◽  
Cancer Development ◽  
Secretory Product ◽  
Prevention And Treatment ◽  
G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

scholarly journals Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Skaidre Jankovskaja ◽  
Johan Engblom ◽  
Melinda Rezeli ◽  
György Marko-Varga ◽  
Tautgirdas Ruzgas ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Relative Increase ◽  
Cancer Biomarker ◽  
Cancer Diagnostics ◽  
Sampling Time ◽  
Skin Permeability ◽  
Experimental Conditions ◽  
Non Invasive

AbstractThe tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.

Vancomycin Adsorption During in vitro Model of Hemoperfusion with HA380 Cartridge

Nephron ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ilaria Godi ◽  
Anna Lorenzin ◽  
Silvia De Rosa ◽  
Gianlorenzo Golino ◽  
Maira Knust ◽  
...  
Keyword(s):  
Complete Removal ◽  
Potential Interaction ◽  
Blood Purification ◽  
Therapeutic Monitoring ◽  
High Concentration ◽  
Langmuir Isotherm Model ◽  
Vitro Model ◽  
Kinetics Of ◽  
Balanced Solution

<b><i>Introduction:</i></b> A critical point for using blood purification during sepsis may be the potential interaction with antimicrobial therapy, the mainstay of sepsis treatment. The aim of our study was to investigate the vancomycin removal during hemoperfusion (HP) using HA380 cartridge. <b><i>Methods:</i></b> This is an experimental study, in which 500 mL of solution was circulated in a closed-circuit (blood flow of 250 mL/min) simulating HP ran using HA380. Vancomycin was added to reach a through concentration or a very high concentration to evaluate the removal ratio (RR) during 120 min of HP. Comparison between blood-crystalloid solution and balanced solution was performed by using Kruskal-Wallis test. The kinetics of vancomycin removal and the adsorption isotherm were evaluated. <b><i>Results:</i></b> We found a complete removal of vancomycin at baseline through concentration of 23.0 ± 7.4 mg/L. Using extremely high concentration (baseline 777.0 ± 62.2 mg/L), RR was 90.1 ± 0.6% at 5 min and 99.2 ± 0.6% at 120 min. No difference in terms of RR was found between blood-crystalloid mixture and balanced solution. The kinetics of the vancomycin reduction followed an exponential decay. Repeated boluses (total amount of 2,000 mg) resulted in cumulative adsorption of 1,919.4 mg with RR of 96.6 ± 1.4%, regardless of the amount injected (100 vs. 500 mg). Vancomycin adsorption onto HA380 followed the Langmuir isotherm model. <b><i>Conclusions:</i></b> A considerable amount of vancomycin was rapidly removed during in vitro HP with HA380. Clinical studies are needed to determine whether this may lead to underdosing. Drug therapeutic monitoring is highly recommended when using HA380 for blood purification in patients receiving vancomycin.

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