scholarly journals Noncompetitive inhibition of human CYP2C9 in vitro by a commercialRhodiola roseaproduct

2017 ◽  
Vol 5 (4) ◽  
pp. e00324 ◽  
Author(s):  
Ole Kristian Forstrønen Thu ◽  
Olav Spigset ◽  
Bent Hellum
Keyword(s):  
Noncompetitive Inhibition

Investigations on Adenosine Diphosphate (ADP) Induced Platelet Adhesiveness in Vitro* Part II. Studies on the Mechanism

1964 ◽  
Vol 11 (02) ◽  
pp. 305-316 ◽  
Author(s):  
B. A Skålhegg ◽  
A. J Hellem ◽  
A. E Ödegaard
Keyword(s):  
Acetic Acid ◽  
Bleeding Time ◽  
Competitive Inhibition ◽  
Adenosine Diphosphate ◽  
Molecular Iodine ◽  
Platelet Adhesiveness ◽  
Noncompetitive Inhibition ◽  
Sh Groups ◽  
Platelet Reaction

SummaryAn attempt to clarify the ADP platelet reaction has been done by investigating the effect of substances which inhibit the reaction in vitro. The inhibitors used may be divided into two groups. Monoiodo acetic acid, molecular iodine, para-chloro mercuribenzoic acid and potassium ferricyanid lead to noncompetitive inhibition. Substances containing free -SH groups and adenine conjugates show competitive inhibition.The primary bleeding time is prolonged when wounds are flushed with solutions of these compounds.It is shown that adenosine tetraphosphate aggregates platelets in the same manner as ADP.Based upon these observations an attempt is made to explain some of the steps involved in the ADP platelet reaction.

scholarly journals Ceramide Synthesis Is Modulated by the Sphingosine Analog FTY720 via a Mixture of Uncompetitive and Noncompetitive Inhibition in an Acyl-CoA Chain Length-de pend ent Manner

2009 ◽  
Vol 284 (24) ◽  
pp. 16090-16098 ◽  
Author(s):  
Sujoy Lahiri ◽  
Hyejung Park ◽  
Elad L. Laviad ◽  
Xuequan Lu ◽  
Robert Bittman ◽  
...  
Keyword(s):  
Chain Length ◽  
Cultured Cells ◽  
De Novo ◽  
Biological Effects ◽  
Sphingolipid Metabolism ◽  
Ceramide Synthase ◽  
Noncompetitive Inhibition ◽  
Ceramide Synthesis ◽  
Ceramide Synthases

FTY720, a sphingosine analog, is in clinical trials as an immunomodulator. The biological effects of FTY720 are believed to occur after its metabolism to FTY720 phosphate. However, very little is known about whether FTY720 can interact with and modulate the activity of other enzymes of sphingolipid metabolism. We examined the ability of FTY720 to modulate de novo ceramide synthesis. In mammals, ceramide is synthesized by a family of six ceramide synthases, each of which utilizes a restricted subset of acyl-CoAs. We show that FTY720 inhibits ceramide synthase activity in vitro by noncompetitive inhibition toward acyl-CoA and uncompetitive inhibition toward sphinganine; surprisingly, the efficacy of inhibition depends on the acyl-CoA chain length. In cultured cells, FTY720 has a more complex effect, with ceramide synthesis inhibited at high (500 nm to 5 μm) but not low (<200 nm) sphinganine concentrations, consistent with FTY720 acting as an uncompetitive inhibitor toward sphinganine. Finally, electrospray ionization-tandem mass spectrometry demonstrated, unexpectedly, elevated levels of ceramide, sphingomyelin, and hexosylceramides after incubation with FTY720. Our data suggest a novel mechanism by which FTY720 might mediate some of its biological effects, which may be of mechanistic significance for understanding its mode of action.

THE INFLUENCE OF SOME HYPOTENSIVE DRUGS ON THE SEROTONERGIC MECHANISMS IN RATS PLATELETS

1987 ◽  
Author(s):  
W Buczko ◽  
M Pietraszek ◽  
E Chabielska ◽  
B Malinowska
Keyword(s):  
Platelet Aggregation ◽  
Mechanism Of Action ◽  
Blood Platelets ◽  
Mechanisms Of Action ◽  
Noncompetitive Inhibition ◽  
Amine Uptake ◽  
Secondary Mechanism ◽  
Therapy Of Hypertension

Serotonin (5HT) is a vasoactive amine that has been reported to be involved in a number of forms of circulatory failure. The 5HT content and metabolism in platelets is changed in hypertension and in peripheral arteriolar diseases. The present study concerns the effect of verapamil (VER), propranolol (PRO) and cap-topril (CAP) - drugs having different hypotensive mechanisms of action, on serotonergic mechanisms in rat blood platelets. In vitro, VER produced noncompetitive inhibition of 14C-5HT uptake (IC50=8.2μM), PRO inhibited the uptake in a competitive fashion (Km =0.9μM), whereas CAP was ineffective. Only PRO released (24%) radioactive 5HT from incubated platelets. Inhibition of amine uptake was also obtained when plateletswere prepared from-irats pretreated with VER (10 mg.kg−1 ), PRO (5 mg.kg−1) or CAP (10 mg.kg−1 ). Moreover, the concentration of endogenous 5HT in blood platelets was reduced after VER and PRO administration. Platelets aggregation induced by ADP was inhibited by VER and CAP. They also diminished the potentiating effect of 5HT on ADP-induced platelet aggregation. It can be concluded that these effects may be a secondary mechanism of action in vivo. Thus “serotonergic component” of studied drugs should be taken under consideration at least in therapy of hypertension.Supported by CPBR, no 11.6

MECHANISM OF THE STIMULATORY EFFECT OF CLOMID® ON AROMATIZATION OF STEROIDS BY HUMAN PLACENTA IN VITRO

1966 ◽  
Vol 51 (4) ◽  
pp. 591-598 ◽  
Author(s):  
Dwain D. Hagerman ◽  
Olive W. Smith ◽  
Caroline F. Day
Keyword(s):  
Human Placenta ◽  
Ovarian Tissue ◽  
Effective Concentration ◽  
Noncompetitive Inhibition ◽  
Significant Acceleration ◽  
Aromatization Reaction ◽  
Major Route ◽  
Minimal Effective Concentration

ABSTRACT The in vitro rate of conversion of testosterone to oestrone and oestradiol by a preparation of human placental microsomes was increased by the addition of Clomid®*. The effect was a function of the amount of Clomid added, the maximum observed being 1.6 times that in control vessels containing no Clomid. Of the cis-trans isomers of Clomid, the form designated as isomer A was three times as effective as isomer B in accelerating aromatization. The minimal effective concentration of the mixed isomers in the incubation mixture was 0.2 mm. The mechanism of this effect was shown to be a noncompetitive inhibition of the NADPH:Cytochrome c oxidoreductase system, thereby interfering with a major route of NADPH disposition in the microsomes and increasing the availability of NADPH for the aromatization reaction. The findings suggest a possible mechanism for a direct stimulatory influence of Clomid upon the ovarian biosynthesis of oestrogens in vivo, although the concentration of the drug required for significant acceleration of placental aromatization in vitro was considerably greater than its probable concentration in ovarian tissue following Clomid administration to women.

Ultrastructural Investigations of the Contractile Filaments of Amoebae

1974 ◽  
Vol 32 ◽  
pp. 188-189
Author(s):  
P.L. Moore
Keyword(s):  
Cytoplasmic Streaming ◽  
Three Dimensional ◽  
Freeze Fracture ◽  
Amoeboid Movement ◽  
Different Types ◽  
Chemical Conditions ◽  
Complete Interpretation

Previous freeze fracture results on the intact giant, amoeba Chaos carolinensis indicated the presence of a fibrillar arrangement of filaments within the cytoplasm. A complete interpretation of the three dimensional ultrastructure of these structures, and their possible role in amoeboid movement was not possible, since comparable results could not be obtained with conventional fixation of intact amoebae. Progress in interpreting the freeze fracture images of amoebae required a more thorough understanding of the different types of filaments present in amoebae, and of the ways in which they could be organized while remaining functional.The recent development of a calcium sensitive, demembranated, amoeboid model of Chaos carolinensis has made it possible to achieve a better understanding of such functional arrangements of amoeboid filaments. In these models the motility of demembranated cytoplasm can be controlled in vitro, and the chemical conditions necessary for contractility, and cytoplasmic streaming can be investigated. It is clear from these studies that “fibrils” exist in amoeboid models, and that they are capable of contracting along their length under conditions similar to those which cause contraction in vertebrate muscles.

In Vitro Induction of Crystals of MT Protein by Vinblastine-Colcemid in Mouse Spermatids

1974 ◽  
Vol 32 ◽  
pp. 132-133
Author(s):  
John J. Wolosewick ◽  
John H. D. Bryan
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Endoplasmic Reticulum ◽  
Nuclear Ring ◽  
Rough Er ◽  
Distal Direction ◽  
In Vitro Induction

Early in spermiogenesis the manchette is rapidly assembled in a distal direction from the nuclear-ring-densities. The association of vesicles of smooth endoplasmic reticulum (SER) and the manchette microtubules (MTS) has been reported. In the mouse, osmophilic densities at the distal ends of the manchette are the organizing centers (MTOCS), and are associated with the SER. Rapid MT assembly and the lack of rough ER suggests that there is an existing pool of MT protein. Colcemid potentiates the reaction of vinblastine with tubulin and was used in this investigation to detect this protein.

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

Immunoenzymatic demonstration of the simultaneous presence of transferrin, hemopexin and albumin in a same hepatocyte and their ultrastructural localization

1978 ◽  
Vol 36 (2) ◽  
pp. 88-89
Author(s):  
M. Kraemer ◽  
J. Foucrier ◽  
J. Vassy ◽  
M.T. Chalumeau
Keyword(s):  
Plasma Proteins ◽  
Rat Hepatocytes ◽  
Ultrastructural Localization ◽  
Carrier Proteins ◽  
Normal Cells ◽  
Adult Rat ◽  
Adult Rat Hepatocytes ◽  
Monospecific Antisera ◽  
Different Levels

Some authors using immunofluorescent techniques had already suggested that some hepatocytes are able to synthetize several plasma proteins. In vitro studies on normal cells or on cells issued of murine hepatomas raise the same conclusion. These works could be indications of an hepatocyte functionnal non-specialization, meanwhile the authors never give direct topographic proofs suitable with this hypothesis.The use of immunoenzymatic techniques after obtention of monospecific antisera had seemed to us useful to bring forward a better knowledge of this problem. We have studied three carrier proteins (transferrin = Tf, hemopexin = Hx, albumin = Alb) operating at different levels in iron metabolism by demonstrating and localizing the adult rat hepatocytes involved in their synthesis.Immunological, histological and ultrastructural methods have been described in a previous work.

Sem Studies of Co-Cr-Mo Surgical Implant Alloy Corrosion Behavior

1982 ◽  
Vol 40 ◽  
pp. 520-521
Author(s):  
Ann Chidester Van Orden ◽  
John L. Chidester ◽  
Anna C. Fraker ◽  
Pei Sung
Keyword(s):  
Electron Microscopy ◽  
Corrosion Behavior ◽  
Anodic Polarization ◽  
Saline Solution ◽  
Saturated Calomel Electrode ◽  
Physiological Saline ◽  
X Ray ◽  
Physiological Saline Solution ◽  
Scanning Electron

The influence of small variations in the composition on the corrosion behavior of Co-Cr-Mo alloys has been studied using scanning electron microscopy (SEM), energy dispersive x-ray analysis (EDX), and electrochemical measurements. SEM and EDX data were correlated with data from in vitro corrosion measurements involving repassivation and also potentiostatic anodic polarization measurements. Specimens studied included the four alloys shown in Table 1. Corrosion tests were conducted in Hanks' physiological saline solution which has a pH of 7.4 and was held at a temperature of 37°C. Specimens were mechanically polished to a surface finish with 0.05 µm A1203, then exposed to the solution and anodically polarized at a rate of 0.006 v/min. All voltages were measured vs. the saturated calomel electrode (s.c.e.).. Specimens had breakdown potentials near 0.47V vs. s.c.e.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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