Dopamine D-1 and D-2 Receptor-mediated Inhibition and Excitation of Caudate Neurons Induced by Respective High and Low Concentrations of Dopamine in vitro

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

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In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646570 ◽

1989 ◽

Vol 61 (02) ◽

pp. 254-258 ◽

Cited By ~ 21

Author(s):

Margaret L Rand ◽

Peter L Gross ◽

Donna M Jakowec ◽

Marian A Packham ◽

J Fraser Mustard

Keyword(s):

Cyclic Amp ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Inhibitory Effects ◽

Low Concentrations ◽

Rabbit Platelets ◽

High Concentrations ◽

In Vitro Effects ◽

Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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Aggregation of Cat Platelets in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654191 ◽

1970 ◽

Vol 23 (03) ◽

pp. 601-620 ◽

Cited By ~ 14

Author(s):

Th. B Tschopp

Keyword(s):

Adenosine Monophosphate ◽

Blood Collection ◽

Base Line ◽

Reversible Aggregation ◽

Low Concentrations ◽

Irreversible Aggregation ◽

High Concentrations ◽

Two Phases ◽

Improved Technique

SummaryAggregation of cat platelets in the citrated plasma is examined by means of Born’s absorptiometer. A marked tendency of the platelets of this species to spontaneous aggregation necessitated first of all the development of an improved technique of blood collection.A hypothesis according to which 5-HT is released from the platelets, explains the absence of oscillations on the base line of the absorptiometer, the absence of platelet swelling, when ADP is added, and the effect of stirring on the aggregation curves in cat PRP. The average volume of cat platelets amounts to 10.46 μ3 when directly fixed in the blood, when fixed from PRP to 12.17 μ3, when fixed from stirred PRP to 13.51 μ3.In low concentrations (0.3-2 μM) ADP produce reversible aggregation; in narrowly restricted, individually dissimilar mean concentrations irreversible aggregation in two phases and in high concentrations, irreversible aggregation in one phase. Like ADP serotonin produces 2 phase irreversible aggregation in concentrations of 3-10 μM, but unlike ADP, the aggregation velocity decreases again with high 5-HT concentrations (>100 μM). Adrenaline does not produce aggregation and it is likely that adenosine and adenosine monophosphate inhibit the aggregation by serotonin but not by ADP. Species differences in the aggregation of human, rabbit and cat platelets are discussed.

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DEVELOPMENT OF APPROACHES FOR DETECTION OF GENOME-INTEGRATED PROVIRAL DNA OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV-1) IN ULTRA LOW CONCENTRATIONS USING THE CRISPR/CAS SYSTEM

Molecular Diagnostics and Biosafety – 2020. Russian national scientific and practical conference with international participation (October, 6–8, 2020): Conference Proceedings ◽

10.36233/978-5-9900432-9-9-118 ◽

2020 ◽

Author(s):

M.A. Tyumentseva ◽

◽

A.I. Tyumentsev ◽

V.G. Akimkin ◽

◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Health Monitoring ◽

Biological Samples ◽

Proviral Dna ◽

Guide Rnas ◽

Ribonucleoprotein Complexes ◽

Low Concentrations ◽

Immunodeficiency Virus ◽

Hiv 1

For the effective functioning of supervisory and health monitoring services, it is necessary to introduce modern molecular technologies into their practice. Therefore, the task of developing new effective methods for detecting pathogen, for example HIV, based on CRISPR/CAS genome editing systems, remains urgent. In the present work, guide RNAs and specific oligonucleotides were developed for preliminary amplification of highly conserved regions of the HIV-1 genome. The developed guide RNAs make it possible to detect single copies of HIV-1 proviral DNA in vitro as part of CRISPR/CAS ribonucleoprotein complexes in biological samples after preliminary amplification.

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Effect of C6-Volatiles on Bioluminescent Plant Pathogens

HortScience ◽

10.21273/hortsci.33.3.557d ◽

1998 ◽

Vol 33 (3) ◽

pp. 557d-557

Author(s):

Jennifer Warr ◽

Fenny Dane ◽

Bob Ebel

Keyword(s):

Biological Activity ◽

Bacterial Growth ◽

Xanthomonas Campestris ◽

Plant Pathogens ◽

Genetically Engineered ◽

The Other ◽

Computer Assisted ◽

Signal Molecules ◽

Low Concentrations

C6 volatile compounds are known to be produced by the plant upon pathogen attack or other stress-related events. The biological activity of many of these substances is poorly understood, but some might produce signal molecules important in host–pathogen interactions. In this research we explored the possibility that lipid-derived C6 volatiles have a direct effect on bacterial plant pathogens. To this purpose we used a unique tool, a bacterium genetically engineered to bioluminesce. Light-producing genes from a fish-associated bacterium were introduced into Xanthomonas campestris pv. campestris, enabling nondestructive detection of bacteria in vitro and in the plant with special computer-assisted camera equipment. The effects of different C6 volatiles (trans-2 hexanal, trans-2 hexen-1-ol and cis-3 hexenol) on growth of bioluminescent Xanthomonas campestris were investigated. Different volatile concentrations were used. Treatment with trans-2 hexanal appeared bactericidal at low concentrations (1% and 10%), while treatments with the other volatiles were not inhibitive to bacterial growth. The implications of these results with respect to practical use of trans-2 hexanal in pathogen susceptible and resistant plants will be discussed.

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Uncertainties Associated with Assessing the Risk of an Endocrine Active Substance in the Canadian Environment

Water Quality Research Journal ◽

10.2166/wqrj.2001.019 ◽

2001 ◽

Vol 36 (2) ◽

pp. 319-330 ◽

Cited By ~ 6

Author(s):

Mark Servos ◽

Don Bennie ◽

Kent Burnison ◽

Philippa Cureton ◽

Nicol Davidson ◽

...

Keyword(s):

Risk Assessment ◽

Endocrine Disruption ◽

Endocrine System ◽

Problem Formulation ◽

Normal Function ◽

Weight Of Evidence ◽

Biological Responses ◽

Low Concentrations ◽

Multigenerational Effects

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.

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Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

Alternatives to Laboratory Animals ◽

10.1177/026119298801600108 ◽

1988 ◽

Vol 16 (1) ◽

pp. 32-37

Author(s):

Margherita Ferro ◽

Anna Maria Bassi ◽

Giorgio Nanni

Keyword(s):

Cell Lines ◽

Cell Cultures ◽

Membrane Lipids ◽

Hepatoma Cell ◽

Positive Control ◽

In Vitro Models ◽

Low Concentrations ◽

Formation Efficiency ◽

Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

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In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽

10.3390/antibiotics10040355 ◽

2021 ◽

Vol 10 (4) ◽

pp. 355

Author(s):

Unai Caballero ◽

Sarah Kim ◽

Elena Eraso ◽

Guillermo Quindós ◽

Valvanera Vozmediano ◽

...

Keyword(s):

Interaction Model ◽

Antifungal Drugs ◽

Health Concern ◽

Candida Auris ◽

Fungistatic Activity ◽

Drug Concentrations ◽

Low Concentrations ◽

Wide Range ◽

Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

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The mechanism of in vitro clot lysis induced by vascular plasminogen activator

Blood ◽

10.1182/blood.v63.6.1331.1331 ◽

1984 ◽

Vol 63 (6) ◽

pp. 1331-1337 ◽

Cited By ~ 16

Author(s):

C Tran-Thang ◽

EK Kruithof ◽

F Bachmann

Keyword(s):

Plasminogen Activator ◽

Whole Blood ◽

Apparent Molecular Weight ◽

Clot Lysis ◽

Initial Concentration ◽

Low Concentrations ◽

Sds Page ◽

Tissue Plasminogen ◽

Low Rate

Abstract The contribution of vascular plasminogen activator (v-PA) to the lysis of whole blood and plasma clots was investigated. v-PA released into the circulation after infusion of deamino-D-arginine vasopressin (DDAVP) was shown to bind quantitatively to plasma clots. Its apparent molecular weight, determined by the SDS-PAGE fibrin-agarose underlay method, was approximately 68,000 daltons, and its activity was quenched by antibodies against human tissue plasminogen activator (t-PA). Clots prepared from post-DDAVP plasma or post-DDAVP whole blood, rich in v- PA, did not lyse when incubated in imidazole buffer or normal plasma, as determined by the release of 125I from radiolabeled clots. However, clots made of v-PA-poor plasma or whole blood, incubated in v-PA-rich plasma, underwent substantial lysis. The concentration of PA in clots incubated in v-PA-rich plasma progressively increased in relation to the initial concentration of v-PA in the surrounding plasma. The results suggest that, at low concentrations of circulating v-PA, a hemostatic plug will lyse at a very low rate. However, when the v-PA concentration in the clot environment is increased, v-PA will accumulate progressively onto fibrin and induce thrombolysis.

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A Novel Niosome-Encapsulated Essential Oil Formulation to Prevent Aspergillus flavus Growth and Aflatoxin Contamination of Maize Grains During Storage

Toxins ◽

10.3390/toxins11110646 ◽

2019 ◽

Vol 11 (11) ◽

pp. 646 ◽

Cited By ~ 6

Author(s):

García-Díaz ◽

Patiño ◽

Vázquez ◽

Gil-Serna

Keyword(s):

Aspergillus Flavus ◽

Fungal Growth ◽

Storage Conditions ◽

Aflatoxin Contamination ◽

Small Scale ◽

Low Concentrations ◽

Oil Formulation ◽

Scale Test ◽

Encapsulation Method

Aflatoxin (AF) contamination of maize is a major concern for food safety. The use of chemical fungicides is controversial, and it is necessary to develop new effective methods to control Aspergillus flavus growth and, therefore, to avoid the presence of AFs in grains. In this work, we tested in vitro the effect of six essential oils (EOs) extracted from aromatic plants. We selected those from Satureja montana and Origanum virens because they show high levels of antifungal and antitoxigenic activity at low concentrations against A. flavus. EOs are highly volatile compounds and we have developed a new niosome-based encapsulation method to extend their shelf life and activity. These new formulations have been successfully applied to reduce fungal growth and AF accumulation in maize grains in a small-scale test, as well as placing the maize into polypropylene woven bags to simulate common storage conditions. In this latter case, the antifungal properties lasted up to 75 days after the first application.

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