Lack of effect of cocaine on lysine and alanine uptake in human placental villi or transfer in perfused human placenta

1995 ◽  
Vol 7 (6) ◽  
pp. 1495 ◽  
Author(s):  
RB Krishna ◽  
M Levitz ◽  
J Dancis
Keyword(s):  
Amino Acid ◽  
Human Placenta ◽  
Clinical Situation ◽  
Experimental Models ◽  
Antipyrine Clearance ◽  
Placental Villi ◽  
Glucose Clearance ◽  
Index Ratio ◽  
Transfer Index

The effect of cocaine on lysine and alanine uptake in human placental villi and transfer across the dually perfused placenta was studied. Uptake (in terms of the intracellular to extracellular distribution ratio) of alanine and lysine was 2.81 +/- 0.30 (n = 5) and 1.45 +/- 0.24 (n = 5) respectively and was unaffected by cocaine (50-500 ng mL(-1) in the incubation medium. In the dually perfused placenta, the clearance index (ratio of amino acid to antipyrine clearance) was 0.35 +/- 0.03 and 0.30 +/- 0.05 and the transfer index (ratio of amino acid to L-glucose clearance) was 2.20 +/- 0.07 and 1.89 +/- 0.29 for lysine and alanine respectively. Cocaine at concentrations of 100 ng mL(-1) or 250 ng mL(-1) had no effect on the clearance of either amino acid. The results of this study indicate that concentrations of cocaine likely to be encountered in vivo do not affect uptake of lysine or alanine by placental villi or transfer across the perfused placental lobule, in contrast with the report that cocaine reduces uptake of alanine by placental vesicles. Experimental models must be critically evaluated before accepting the results as pertinent to a clinical situation.

scholarly journals Alanine uptake activates hepatocellular chloride channels

1997 ◽  
Vol 273 (4) ◽  
pp. G849-G853 ◽  
Author(s):  
Steven D. Lidofsky ◽  
Richard M. Roman
Keyword(s):  
Amino Acid ◽  
Mammalian Cells ◽  
Chloride Channels ◽  
Amino Acid Uptake ◽  
Experimental Models ◽  
Cell Swelling ◽  
Acid Uptake ◽  
Adaptive Responses ◽  
Anion Channels

Cells involved in the retrieval and metabolic conversion of amino acids undergo significant increases in size in response to amino acid uptake. The resultant adaptive responses to cell swelling are thought to include increases in membrane K+ and Cl− permeability through activation of volume-sensitive ion channels. This viewpoint is largely based on experimental models of hypotonic swelling, but few mammalian cells experience hypotonic challenge in vivo. Here we have examined volume regulatory responses in a physiological model of cell-swelling alanine uptake in immortalized hepatocytes. Alanine-induced cell swelling was followed by a decrease in cell volume that was temporally associated with an increase in membrane Cl− currents. These currents were dependent both on alanine concentration and Na+, suggesting that currents were stimulated by Na+-coupled alanine uptake. Cl− currents were outwardly rectifying, exhibited an anion permeability sequence of I− > Br− > Cl−, and were inhibited by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid, features similar to those reported for a widely distributed class of volume-sensitive anion channels evoked by experimental hypotonic stress. These findings suggest that volume-sensitive anion channels participate in adaptive responses to amino acid uptake and provide such channels with a new physiological context.

scholarly journals Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and its Analogs in Animal Experimental Models

2021 ◽  
Author(s):  
Michał Zimecki ◽  
Krzysztof Kaczmarek
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Peptide Bond ◽  
Mechanisms Of Action ◽  
Experimental Models ◽  
Amino Acid Residues ◽  
Modified Peptides ◽  
Immunosuppressive Potency

The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds and its linear precursor on their biological activities and mechanisms of action are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

scholarly journals Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and Its Analogs in Animal Experimental Models

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2538
Author(s):  
Michał Zimecki ◽  
Krzysztof Kaczmarek
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Peptide Bond ◽  
Mechanisms Of Action ◽  
Experimental Models ◽  
Amino Acid Residues ◽  
Modified Peptides ◽  
Immunosuppressive Potency

The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds, and its linear precursor on their biological activities and mechanisms of action, are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Site Specific Incorporation of Amino Acid Analogues into Proteins In Vivo

2000 ◽  
Author(s):  
Anne K. Kowal ◽  
Caroline Kohrer ◽  
Uttam L. RajBhandary
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Amino Acid Analogues

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

An Overview of Stroke: Mechanism, In vivo Experimental Models Thereof, and Neuroprotective Agents

2020 ◽  
Vol 21 (9) ◽  
pp. 860-877
Author(s):  
Mohd Muazzam Khan ◽  
Badruddeen ◽  
Mohd Mujahid ◽  
Juber Akhtar ◽  
Mohammad Irfan Khan ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Active Form ◽  
Experimental Models ◽  
Global Cerebral Ischemia ◽  
Channel Blockers ◽  
Neuroprotective Agents ◽  
Decisive Action ◽  
Stroke Mechanism ◽  
Injury Outcomes

Background: Stroke is one of the causes of death and disability globally. Brain attack is because of the acute presentation of stroke, which highlights the requirement for decisive action to treat it. Objective: The mechanism and in-vivo experimental models of stroke with various neuroprotective agents are highlighted in this review. Method: The damaging mechanisms may proceed by rapid, nonspecific cell lysis (necrosis) or by the active form of cell death (apoptosis or necroptosis), depending upon the duration and severity and of the ischemic insult. Results: Identification of injury mediators and pathways in a variety of experimental animal models of global cerebral ischemia has directed to explore the target-specific cytoprotective strategies, which are critical to clinical brain injury outcomes. Conclusion: The injury mechanism, available encouraging medicaments thereof, and outcomes of natural and modern medicines for ischemia have been summarized. In spite of available therapeutic agents (thrombolytics, calcium channel blockers, NMDA receptor antagonists and antioxidants), there is a need for an ideal drug for strokes.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

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